Dehai Li

Name:

Organization: Ocean University of China

Department: Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy

Title:

Chemicals
References

Late-Stage Terpene Cyclization by an Integral Membrane Cyclase in the Biosynthesis of Isoprenoid Epoxycyclohexenone Natural Products

Co-reporter:Man-Cheng Tang, Xiaoqing Cui, Xueqian He, Zhuang Ding, Tianjiao Zhu, Yi Tang, and Dehai Li

Organic Letters October 6, 2017 Volume 19(Issue 19) pp:

Publication Date(Web):September 19, 2017

DOI:10.1021/acs.orglett.7b02653

Macrophorins are representative examples of isoprenoid epoxycyclohexenones containing cyclized drimane moieties. We located and characterized the biosynthetic gene cluster of macrophorin from Penicillium terrestris. MacJ encoded by this cluster was characterized to be the first example of a membrane-bound type-II terpene cyclase catalyzing the cyclization of meroterpenoids via direct protonation of the terminal olefinic bond in acyclic yanuthones. The late-stage functionalization and substrate promiscuity of MacJ make it a potential biocatalyst for the synthesis of macrophorin analogues.

Geranylpyrrol A and Piericidin F from Streptomyces sp. CHQ-64 ΔrdmF

Co-reporter:Xiaoning Han, Zengzhi Liu, Zhenzhen Zhang, Xiaomin Zhang, Tianjiao Zhu, Qianqun Gu, Wenli Li, Qian Che, and Dehai Li

Journal of Natural Products May 26, 2017 Volume 80(Issue 5) pp:1684-1684

Publication Date(Web):April 18, 2017

DOI:10.1021/acs.jnatprod.7b00016

Two new compounds, geranylpyrrol A (1) and piericidin F (2), were isolated from a reedsmycins nonproducing mutant strain of Streptomyces sp. CHQ-64. Their structures, including absolute configurations, were elucidated by extensive NMR, MS, NOESY, and ECD analyses. Geranylpyrrol A (1) is an unusual naturally occurring 2,3,4-trisubstituted pyrrole, and piericidin F (2) showed cytotoxicity against HeLa, NB4, A549, and H1975 cell lines with IC50 values of 0.003, 0.037, 0.56, and 0.49 μM, respectively.

N-Me-trichodermamide B isolated from Penicillium janthinellum, with antioxidant properties through Nrf2-mediated signaling pathway

Co-reporter:Zhen Yang, Mei-lin Zhu, De-hai Li, Rong Zeng, Bing-nan Han

Bioorganic & Medicinal Chemistry 2017 Volume 25, Issue 24(Issue 24) pp:

Publication Date(Web):15 December 2017

DOI:10.1016/j.bmc.2017.10.044

•A new trichodermamide-like alkaloid was isolated from a marine fungus Penicillium janthinellum HDN13-309.•This new alkaloid exhibited cellular protection from the H2O2-induced oxidative damage.•The antioxidant properties of this new alkaloid were confirmed through Nrf2-mediated signaling pathway.A new trichodermamide-like alkaloid, N-Me-trichodermamide B (compound 1), was isolated from a marine fungus Penicillium janthinellum HDN13-309. The structure and absolute configuration of compound 1 were determined by extensive NMR analysis and the modified Mosher’s method. This new alkaloid exhibited cellular protection from the H2O2-induced oxidative damage, and the mechanism study revealed that this antioxidant activity was regulated through Nrf2-mediated signaling pathway in HaCaT human keratinocytes. In addition, the inhibitor of p38 abrogated compound 1-induced phosphorylation of p38, up-expression of HO-1, and the nuclear localization of Nrf2. As a result, it suggested that this new alkaloid-induced antioxidant signaling pathway might be initiated through activation of p38.Download high-res image (69KB)Download full-size image

Trichodermamides D–F, heterocyclic dipeptides with a highly functionalized 1,2-oxazadecaline core isolated from the endophytic fungus Penicillium janthinellum HDN13-309

Co-reporter:Meilin Zhu;Zhen Yang;Huimin Feng;Qi Gan;Qian Che;Tianjiao Zhu;Qianqun Gu;Bingnan Han

RSC Advances (2011-Present) 2017 vol. 7(Issue 76) pp:48019-48024

Publication Date(Web):2017/10/11

DOI:10.1039/C7RA10389A

Three new heterocyclic dipeptides with a highly functionalized 1,2-oxazadecaline core, named trichodermamides D–F (1–3), together with the known trichodermamides A–C (4–6), were isolated from the broth of the mangrove-derived endophytic fungus Penicillium janthinellum HDN13-309. The structures were elucidated through extensive NMR spectroscopic and physical data. The absolute configurations of compounds 1–3 were determined by ECD calculations and single-crystal X-ray diffraction experiments. The cytoprotective activities were evaluated on different phase II detoxifying enzymes (SOD2, AKR1C1, HO-1 and NQO1), and compounds 4 and 6 showed potent inducing effects at the concentration of 10 μM.

Penicisulfuranols A–F, Alkaloids from the Mangrove Endophytic Fungus Penicillium janthinellum HDN13-309

Co-reporter:Meilin Zhu, Xiaomin Zhang, Huimin Feng, Jiajia Dai, Jing Li, Qian Che, Qianqun Gu, Tianjiao Zhu, and Dehai Li

Journal of Natural Products 2017 Volume 80(Issue 1) pp:

Publication Date(Web):December 19, 2016

DOI:10.1021/acs.jnatprod.6b00483

Six new epipolythiodioxopiperazine (ETP) alkaloids, penicisulfuranols A–F (1–6), were isolated from the mangrove endophytic fungus Penicillium janthinellum HDN13-309. All structures including absolute configurations were elucidated on the basis of comprehensive spectroscopic data and ECD calculations. They belong to the unusual family of ETPs containing sulfur atoms on both α- and β-positions of amino acid residues and a rare 1,2-oxazadecaline core moiety. In addition, compounds 1–6 also possess a rare spiro-furan ring and 1–3 showed cytotoxicity with IC50 values ranging from 0.1 to 3.9 μM.

Naquihexcin A, a S-Bridged Pyranonaphthoquinone Dimer Bearing an Unsaturated Hexuronic Acid Moiety from a Sponge-Derived Streptomyces sp. HDN-10-293

Co-reporter:Qian Che, Hongsheng Tan, Xiaoning Han, Xiaomin Zhang, Qianqun Gu, Tianjiao Zhu, and Dehai Li

Organic Letters 2016 Volume 18(Issue 14) pp:3358-3361

Publication Date(Web):June 24, 2016

DOI:10.1021/acs.orglett.6b01485

S-Bridged pyranonaphthoquinone dimers, naquihexcins A and B (1 and 2), together with a related analogue (−)-BE-52440A (3) were obtained from the culture of a sponge-derived Streptomyces sp. HDN-10-293. Naquihexcin A (1) bears a rare unsaturated hexuronic acid moiety, and (−)-BE-52440A (3) has been discovered from natural resources. Compound 3 showed cytotoxicity against NB4 and HL-60 cells, while 1 could inhibit the proliferation of the adriamycin resistant human breast cancer cell line MCF-7 ADM.

Isoindolone-Containing Meroperpenoids from the Endophytic Fungus Emericella nidulans HDN12-249

Co-reporter:Haibo Zhou, Xinhua Sun, Na Li, Qian Che, Tianjiao Zhu, Qianqun Gu, and Dehai Li

Organic Letters 2016 Volume 18(Issue 18) pp:4670-4673

Publication Date(Web):September 2, 2016

DOI:10.1021/acs.orglett.6b02297

Six isoindolone containing meroterpenoids, emericellolides A–C (1–3) and emeriphenolicins E–G (4–6), were isolated from a plant endophytic fungus Emericella nidulans HDN12-249. Emericellolides A–C (1–3) feature the unprecedented macrolide skeleton composed of an unusual l-glutamate fragment, an isoindolone unit, and a sesquiterpene moiety, while structures of emeriphenolicins E–G (4–6) with two farnesyl groups attached to one isoindolone unit are rare in isoindolone-derived meroterpenoids. These structures including the absolute configurations were established on the basis of MS, NMR, Mo2(AcO)4-induced ECD, Marfey’s method, and chemical conversion. Compound 4 exhibited cytotoxicity against HeLa cells with IC50 value of 4.77 μM.

Neosartoryadins A and B, Fumiquinazoline Alkaloids from a Mangrove-Derived Fungus Neosartorya udagawae HDN13-313

Co-reporter:Guihong Yu; Guoliang Zhou; Meilin Zhu; Wei Wang; Tianjiao Zhu; Qianqun Gu

Organic Letters 2016 Volume 18(Issue 2) pp:244-247

Publication Date(Web):December 29, 2015

DOI:10.1021/acs.orglett.5b02964

Neosartoryadins A (1) and B (2), both with a unique 6/6/6/5 quinazoline ring system connected directly to a 6/5/5 imidazoindolone ring, together with three biogenetically related compounds 3–5, were isolated from the endophytic fungus Neosartorya udagawae HDN13-313. The absolute configurations of new compounds 1–4 were established. Compounds 1 and 2 displayed anti-influenza virus A (H1N1) activities with IC50 values of 66 and 58 μM, respectively (ribavirin as positive control, IC50 = 94 μM).

Penipyridones A–F, Pyridone Alkaloids from Penicillium funiculosum

Co-reporter:Haibo Zhou; Liyuan Li; Chongming Wu; Tibor Kurtán; Attila Mándi; Yankai Liu; Qianqun Gu; Tianjiao Zhu; Peng Guo

Journal of Natural Products 2016 Volume 79(Issue 7) pp:1783-1790

Publication Date(Web):June 30, 2016

DOI:10.1021/acs.jnatprod.6b00218

Six new pyridone alkaloids, named penipyridones A–F (1–6), were isolated from the fermentation broth of an Antarctic moss-derived fungus, Penicillium funiculosum GWT2-24. Their structures were elucidated from extensive NMR and MS data. Although they possess the same major chromophore and some of them presented almost mirror ECD spectra, their absolute configurations were found to be uniformly S, as evidenced by X-ray single-crystal diffraction analysis, stereocontrolled total synthesis, and chemical conversions. TDDFT-ECD calculations of compounds 3 and 6 revealed that subtle conformational changes are responsible for the significantly different ECD curves. None of the compounds were cytotoxic (IC50 > 50 μM), while compounds 1, 2, 5, and 7 elicited lipid-lowering activity in HepG2 hepatocytes.

Clindanones A and B and cladosporols F and G, polyketides from the deep-sea derived fungus Cladosporium cladosporioides HDN14-342

Co-reporter:Zhenzhen Zhang, Xueqian He, Congcong Liu, Qian Che, Tianjiao Zhu, Qianqun Gu and Dehai Li

RSC Advances 2016 vol. 6(Issue 80) pp:76498-76504

Publication Date(Web):03 Aug 2016

DOI:10.1039/C6RA14640F

Four new tetralone derivatives, clindanones A and B (1 and 2) and cladosporols F and G (3 and 4), together with three known biogenetically related polyketides (5–7), were isolated from the deep-sea derived fungus Cladosporium cladosporioides HDN14-342. The structures of 1–4, including absolute configurations, were deduced based on MS, NMR and TD-DFT calculations of specific ECD spectra. The absolute configurations of the known cladosporols C (5) and E (6) were also revised. Compounds 1 and 2 possessed new dimeric forms of the skeleton composed by coupling of indanone and 1-tetralone units, and 4 showed the best cytotoxic activity against HeLa cells with an IC50 value of 3.9 μM.

Campyridones A–D, pyridone alkaloids from a mangrove endophytic fungus Campylocarpon sp. HDN13-307

Co-reporter:Meilin Zhu, Xiaomin Zhang, Huimin Feng, Qian Che, Tianjiao Zhu, Qianqun Gu, Dehai Li

Tetrahedron 2016 Volume 72(Issue 37) pp:5679-5683

Publication Date(Web):15 September 2016

DOI:10.1016/j.tet.2016.07.080

Two pairs of epimers, campyridones A and B (1 and 2) and campyridones C and D (3 and 4), were isolated from the mangrove endophytic fungus Campylocarpon sp. HDN13-307, as well as the biogenetically related known ilicicolin H (5). Their structures including absolute configurations were elucidated on the basis of the spectroscopic analysis and ECD calculations. The new compounds 1–4 possess unprecedented ring systems featured by the appearance of an additional spiro-furanone (1/2) or γ-pyrone (3/4) moieties (C ring), which represents a new family of 4-hydroxy-2-pyridone alkaloids. Compounds 4 and 5 were cytotoxic against Hela cell with IC50 values of 8.8 μM and 4.7 μM, respectively. A plausible biosynthetic pathway for 1–4 is also elucidated.

Varitatin A, a Highly Modified Fatty Acid Amide from Penicillium variabile Cultured with a DNA Methyltransferase Inhibitor

Co-reporter:Xueqian He; Zhenzhen Zhang; Yinghan Chen; Qian Che; Tianjiao Zhu; Qianqun Gu

Journal of Natural Products 2015 Volume 78(Issue 11) pp:2841-2845

Publication Date(Web):November 12, 2015

DOI:10.1021/acs.jnatprod.5b00742

A new, highly modified fatty acid amide, varitatin A (1), was isolated from the fungus Penicillium variabile HXQ-H-1 cultivated with the DNA methyltransferase inhibitor 5-azacytidine. The structure including the absolute configuration of 1 was established by analysis of NMR and MS data, together with chemical degradation and Mosher’s method based on MPA esters. Compound 1 showed cytotoxicity against HCT-116 cells with an IC50 value of 2.8 μM and also inhibited the effects of protein tyrosine kinases.

Penicitols A–C and Penixanacid A from the Mangrove-Derived Penicillium chrysogenum HDN11-24

Co-reporter:Wenqiang Guo; Dan Li; Jixing Peng; Tianjiao Zhu; Qianqun Gu

Journal of Natural Products 2015 Volume 78(Issue 2) pp:306-310

Publication Date(Web):January 22, 2015

DOI:10.1021/np500586r

Three new citrinin analogues, penicitols A–C (1–3), and one new xanthone derivative, penixanacid A (4), together with four known biogenetically related compounds (5–8), were discovered from the extract of a mangrove-derived fungus, Penicillium chrysogenum HND11-24. The structures of penicitols A–C and penixanacid A were established through analysis of extensive spectroscopic data. Their cytotoxic activity against HeLa, BEL-7402, HEK-293, HCT-116, and A549 cell lines was evaluated.

Versixanthones A–F, Cytotoxic Xanthone–Chromanone Dimers from the Marine-Derived Fungus Aspergillus versicolor HDN1009

Co-reporter:Guangwei Wu; Guihong Yu; Tibor Kurtán; Attila Mándi; Jixing Peng; Xiaomei Mo; Ming Liu; Hui Li; Xinhua Sun; Jing Li; Tianjiao Zhu; Qianqun Gu

Journal of Natural Products 2015 Volume 78(Issue 11) pp:2691-2698

Publication Date(Web):October 27, 2015

DOI:10.1021/acs.jnatprod.5b00636

Six unusual xanthone–chromanone dimers, versixanthones A–F (1–6), featuring different formal linkages of tetrahydroxanthone and 2,2-disubstituted chroman-4-one monomers, were isolated from a culture of the mangrove-derived fungus Aspergillus versicolor HDN1009. The absolute configurations of 1–6, representing the central and axial chirality elements or preferred helicities, were established by a combination of X-ray diffraction analysis, chemical conversions, and TDDFT-ECD calculations. The interconversion of different biaryl linkages between 1 and 4 and between 2 and 3 in DMSO by a retro-oxa-Michael mechanism provided insight into the formation of the xanthone–chromanone dimers and supported the assignments of their absolute configurations. Compounds 1–6 exhibited cytotoxicities against the seven tested cancer cell lines, with the best IC50 value of 0.7 μM. Compound 5 showed further inhibitory activity against topoisomerase I.

Penicyclones A–E, Antibacterial Polyketides from the Deep-Sea-Derived Fungus Penicillium sp. F23-2

Co-reporter:Wenqiang Guo; Zhenzhen Zhang; Tianjiao Zhu; Qianqun Gu

Journal of Natural Products 2015 Volume 78(Issue 11) pp:2699-2703

Publication Date(Web):November 5, 2015

DOI:10.1021/acs.jnatprod.5b00655

Five new ambuic acid analogues, penicyclones A–E (1–5), were isolated from the extract of the deep-sea-derived fungus Penicillium sp. F23-2. The structures including the absolute configurations were established by interpretation of NMR and MS data, as well as the application of ECD, X-ray crystallography, and a chemical conversion, as well as the TDDFT-ECD calculations. Penicyclones A–E (1–5) exhibited antimicrobial activity against the Gram-positive bacterium Staphylococcus aureus with MIC values ranging from 0.3 to 1.0 μg/mL.

Genome scanning inspired isolation of reedsmycins A–F, polyene-polyol macrolides from Streptomyces sp. CHQ-64

Co-reporter:Qian Che, Tong Li, Xiaofang Liu, Tingting Yao, Jing Li, Qianqun Gu, Dehai Li, Wenli Li and Tianjiao Zhu

RSC Advances 2015 vol. 5(Issue 29) pp:22777-22782

Publication Date(Web):23 Feb 2015

DOI:10.1039/C4RA15415K

Genome scanning of the reed rhizosphere soil-derived Streptomyces sp. CHQ-64 revealed a partial gene cluster, putatively encoding a polyene-polyol compound. Inspired by this finding, six new polyene-polyol macrolides, reedsmycins A–F (1–6), were isolated guided by the characteristic NMR signals. Their structures were elucidated using mass spectrometry and extensive NMR spectroscopy. Among them, reedsmycin F (6) possessed a rare 31-membered macroring containing a tetrahydrofuran motif, and reedsmycin A (1) exhibited promising activity against Candida albicans with a MIC of 25–50 μM, in a comparable level to that of the positive control nystatin.

Lipid-lowering polyketides from a soft coral-derived fungus Cladosporium sp. TZP29

Co-reporter:Meilin Zhu, Huquan Gao, Chongming Wu, Tianjiao Zhu, Qian Che, Qianqun Gu, Peng Guo, Dehai Li

Bioorganic & Medicinal Chemistry Letters 2015 Volume 25(Issue 17) pp:3606-3609

Publication Date(Web):1 September 2015

DOI:10.1016/j.bmcl.2015.06.072

Two new C12 polyketides, cladospolides E and F (1 and 2), together with four known derivatives seco-patulolides A and C (3 and 4), 11-hydroxy-γ-dodecalactone (5) and iso-cladospolide B (6), were isolated from a soft coral-derived fungus Cladosporium sp. TZP-29. Their structures, including the absolute configurations, were elucidated by spectroscopic analysis, modified Mosher’s method, and the analysis of their biogenesis. All compounds were non-cytotoxic while compounds 1 and 3–5 showed potent lipid-lowering activity in HepG2 hepatocytes.

Stachybotrin G, a sulfate meroterpenoid from a sponge derived fungus Stachybotrys chartarum MXH-X73

Co-reporter:Xinhua Ma, Haotian Wang, Feng Li, Tianjiao Zhu, Qianqun Gu, Dehai Li

Tetrahedron Letters 2015 Volume 56(Issue 50) pp:7053-7055

Publication Date(Web):16 December 2015

DOI:10.1016/j.tetlet.2015.11.029

Stachybotrin G (1), a new sulfate meroterpenoid possessing a unique farnesylated [1,3]diazepino[2,1-a]isoindole skeleton, was discovered from sponge derived fungus Stachybotrys chartarum (MXH-X73). The structure was elucidated on the basis of NMR spectroscopic data and X-ray analysis.

Okaramines S–U, three new indole diketopiperazine alkaloids from Aspergillus taichungensis ZHN-7-07

Co-reporter:Shengxin Cai, Shiwei Sun, Jixing Peng, Xianglan Kong, Huinan Zhou, Tianjiao Zhu, Qianqun Gu, Dehai Li

Tetrahedron 2015 Volume 71(Issue 22) pp:3715-3719

Publication Date(Web):3 June 2015

DOI:10.1016/j.tet.2014.09.019

Three new indole diketopiperazine alkaloids, okaramines S–U (1–3), with two (1 and 2) of them prenylated, were obtained from the Aspergillus taichungensis ZHN-7-07. Their structures including the absolute configurations were determined by combination of NMR, MS, TDDFT ECD calculation, and Marfey's analysis. Okaramine S (1) showed the best cytotoxic activity against HL-60 cell with IC50 value of 0.78 μM.

Speradines B-D, oxygenated cyclopiazonic acid alkaloids from the sponge-derived fungus Aspergillus flavus MXH-X104

Co-reporter:Xinhua Ma, Jixing Peng, Guangwei Wu, Tianjiao Zhu, Guoqiang Li, Qianqun Gu, Dehai Li

Tetrahedron 2015 Volume 71(Issue 21) pp:3522-3527

Publication Date(Web):27 May 2015

DOI:10.1016/j.tet.2015.03.050

Two new highly oxygenated hexacyclic cyclopiazonic acid (CPA) alkaloids, speradines B and C (1 and 2), together with one new related tetracyclic oxindole alkaloid, speradine D (3), were isolated from the sponge derived fungus Aspergillus flavus MXH-X104. Among them, speradine C (2) possesses unprecedented 6/5/6/5/5/6 hexacyclic ring system and 4-oxo-1, 3-oxazinane ring. The structures including absolute configurations of 1–3 were deduced from the spectroscopic data, X-ray diffraction analysis and the computational method including the calculation of the chemical shifts and the electronic circular dichroism (ECD) spectra.

Psychrophilins E–H and Versicotide C, Cyclic Peptides from the Marine-Derived Fungus Aspergillus versicolor ZLN-60

Co-reporter:Jixing Peng ; Huquan Gao ; Xiaomin Zhang ; Shuai Wang ; Chongming Wu ; Qianqun Gu ; Peng Guo ; Tianjiao Zhu

Journal of Natural Products 2014 Volume 77(Issue 10) pp:2218-2223

Publication Date(Web):September 23, 2014

DOI:10.1021/np500469b

Four new cyclic peptides, psychrophilins E–H (1–4), possessing a rare amide linkage between the carboxylic acid in anthranilic acid (ATA) and the nitrogen from an indole moiety, along with a new ATA-containing hexapeptide, versicotide C (5), were obtained from the culture of the marine-derived fungus Aspergillus versicolor ZLN-60. The structures, including absolute configurations, were elucidated by a combination of HRESIMS, NMR, X-ray crystallography, TDDFT ECD calculations, and Marfey’s method. Versicotide C (5) is the first natural cyclic hexapeptide containing two anthranilic acids. Compounds 1–5 were not cytotoxic, and compound 3 showed potent lipid-lowering effects.

Sorbicatechols A and B, Antiviral Sorbicillinoids from the Marine-Derived Fungus Penicillium chrysogenum PJX-17

Co-reporter:Jixing Peng ; Xiaomin Zhang ; Lin Du ; Wei Wang ; Tianjiao Zhu ; Qianqun Gu

Journal of Natural Products 2014 Volume 77(Issue 2) pp:424-428

Publication Date(Web):February 4, 2014

DOI:10.1021/np400977e

Two novel sorbicillinoids combining a bicyclo[2.2.2]octane with a 2-methoxyphenol moiety, named sorbicatechols A (1) and B (2), were isolated from the culture of the marine sediment-derived fungus Penicillium chrysogenum PJX-17, together with the known protocatechuic acid methyl ester and caffeic acid methyl ester (3). Their structures, including absolute configurations, were assigned by analysis of NMR, MS data, and TDDFT ECD calculations. Compounds 1 and 2 exhibited activities against influenza virus A (H1N1), with IC50 values of 85 and 113 μ M, respectively.

Cladosins A–E, Hybrid Polyketides from a Deep-Sea-Derived Fungus, Cladosporium sphaerospermum

Co-reporter:Guangwei Wu ; Xinhua Sun ; Guihong Yu ; Wei Wang ; Tianjiao Zhu ; Qianqun Gu

Journal of Natural Products 2014 Volume 77(Issue 2) pp:270-275

Publication Date(Web):February 5, 2014

DOI:10.1021/np400833x

Five new fungal hybrid polyketides, cladosins A–D (1–4), that contain a novel linear 6(3)-enamino-8,10-dihydroxy-tetraketide (1 and 2) or 6-enamino-7(8)-en-10-ol (3 and 4) moiety, as well as the biogenetically related cladosin E (5), were isolated from the deep-sea-derived fungus Cladosporium sphaerospermum 2005-01-E3. Their structures (1–5) were elucidated through a combination of spectroscopic data, chemical conversion, and both Mosher’s and Marfey’s methods for stereochemical assignment. A plausible biogenetic pathway to 1–5 is proposed. Cladosin C (3) possesses mild anti-influenza A H1N1 virus activity.

Eleganketal A, a Highly Oxygenated Dibenzospiroketal from the Marine-Derived Fungus Spicaria elegans KLA03

Co-reporter:Yepeng Luan ; Hongjuan Wei ; Zhenpei Zhang ; Qian Che ; Yankai Liu ; Tianjiao Zhu ; Attila Mándi ; Tibor Kurtán ; Qianqun Gu

Journal of Natural Products 2014 Volume 77(Issue 7) pp:1718-1723

Publication Date(Web):June 26, 2014

DOI:10.1021/np500458a

Eleganketal A (1), a naturally occurring aromatic polyketide possessing a rare highly oxygenated spiro[isobenzofuran-1,3′-isochroman] ring system, was isolated from the fungus Spicaria elegans KLA03 by culturing it in a modified mannitol-based medium. The structure of 1 including the absolute configuration was determined by combining spectroscopic analysis, synthesis of the racemic permethylated analogue, chiral-phase HPLC separation, and TDDFT-ECD analysis.

Corrigendum to “Aspergilazine A, a diketopiperazine dimer with a Rare N-1 to C-6 linkage, from a marine-derived fungus Aspergillus taichungensis” [Tetrahedron Lett. 53 (2012) 2615–2617]

Co-reporter:Shengxin Cai, Xianglan Kong, Wei Wang, Huinan Zhou, Tianjiao Zhu, Dehai Li, Qianqun Gu

Tetrahedron Letters 2014 Volume 55(Issue 39) pp:5404

Publication Date(Web):24 September 2014

DOI:10.1016/j.tetlet.2014.07.001

Prenylated Indole Diketopiperazines from the Marine-Derived Fungus Aspergillus versicolor

Co-reporter:Jixing Peng, Huquan Gao, Jing Li, Jing Ai, Meiyu Geng, Guojian Zhang, Tianjiao Zhu, Qianqun Gu, and Dehai Li

The Journal of Organic Chemistry 2014 Volume 79(Issue 17) pp:7895-7904

Publication Date(Web):August 4, 2014

DOI:10.1021/jo5010179

Seven new prenylated indole diketopiperazines, versicamides A–G (1–7) and a novel chemical derivative from 7, versicamide H (8), along with three known analogic diketopiperazines (9–11) were obtained from the marine-derived fungus Aspergillus versicolor HDN08-60. Their structures were determined by spectroscopic techniques, including 2D NMR, ECD calculations, and single-crystal X-ray diffraction analysis, together with the assistance of further chemical conversions. The cytotoxicities of 1–8 were tested against the HeLa, HCT-116, HL-60, and K562 cell lines, but only 8 exhibited moderate activity against HL-60 cells, with an IC50 value of 8.7 μM. Further investigation with target screening showed that 8 exhibited selective PTK inhibitory activities.

Isolation and Photoinduced Conversion of 6-epi-Stephacidins from Aspergillus taichungensis

Co-reporter:Shengxin Cai, Yepeng Luan, Xianglan Kong, Tianjiao Zhu, Qianqun Gu, and Dehai Li

Organic Letters 2013 Volume 15(Issue 9) pp:2168-2171

Publication Date(Web):April 3, 2013

DOI:10.1021/ol400694h

Three prenylated indole alkaloids with a rare anti bicyclo-[2.2.2]diazaoctane core ring (5–7) were isolated from Aspergillus taichungensis. The structures including absolute configurations were elucidated based on NMR, X-ray, and CD methods. (+)-Versicolamides B and C (8–9) which contain a spiro-center, together with seven analogues (7, 10–15), were isolated as photoinduced conversion products of 6. Biological evaluation indicated that 6 and 7 exhibited significant cytotoxicities with IC50 values in the low micromolar range.

Polycyclic Hybrid Isoprenoids from a Reed Rhizosphere Soil Derived Streptomyces sp. CHQ-64

Co-reporter:Qian Che, Tianjiao Zhu, Robert A. Keyzers, Xiaofang Liu, Jing Li, Qianqun Gu, and Dehai Li

Journal of Natural Products 2013 Volume 76(Issue 4) pp:759-763

Publication Date(Web):April 2, 2013

DOI:10.1021/np3008864

Two new hybrid isoprenoids, named indotertine B (2) and drimentine H (3), along with the known analogue drimentine C (4), were isolated from the reed rhizosphere soil derived actinomycete Streptomyces sp. CHQ-64. The structures of these compounds, including absolute configurations, were elucidated by extensive NMR, MS, and CD analyses. Indotertine B (2) exists as a pair of rotamers about the N–C(O) bond with a 2:1 ratio and displays activities against HCT-8 and A549 tumor cell lines with IC50 values of 6.96 and 4.88 μM, respectively.

Meroterpenoids with Diverse Ring Systems from the Sponge-Associated Fungus Alternaria sp. JJY-32

Co-reporter:Guojian Zhang ; Guangwei Wu ; Tianjiao Zhu ; Tibor Kurtán ; Attila Mándi ; Jieying Jiao ; Jing Li ; Xin Qi ; Qianqun Gu

Journal of Natural Products 2013 Volume 76(Issue 10) pp:1946-1957

Publication Date(Web):October 15, 2013

DOI:10.1021/np4005757

Fifteen meroterpenoids (1–15) with diverse ring systems including an unprecedented oxaspiro[5.5]nonane-fused cyclohexenone (1), hydrogenated benzofurans (2–5), hydrogenated chromans (6, 7), hydrogenated cyclopenta[b]chromans (8–11), and four monocyclic structures (12–15) were isolated from the sponge-associated fungus Alternaria sp. JJY-32. The structures were elucidated by detailed spectroscopic analysis, including 2D NMR and electronic circular dichroism (ECD) calculations, and assisted by chemical derivatizations. On the basis of supplementation experiments with specific enzyme inhibitors and putative precursors, a shikimate–isoprenoid hybrid biosynthetic pathway is proposed. The NF-κB inhibitory activities of 1–15 were tested, and all of them, except 6 and 7 (IC50 > 100 μM), showed activities with IC50 values ranging from 39 to 85 μM in RAW264.7 cells.

Phenylspirodrimanes with Anti-HIV Activity from the Sponge-Derived Fungus Stachybotrys chartarum MXH-X73

Co-reporter:Xinhua Ma, Letao Li, Tianjiao Zhu, Mingyu Ba, Guoqiang Li, Qianqun Gu, Ying Guo, and Dehai Li

Journal of Natural Products 2013 Volume 76(Issue 12) pp:2298-2306

Publication Date(Web):December 5, 2013

DOI:10.1021/np400683h

Seven new phenylspirodrimanes, named stachybotrins D–F (1, 3, 4), stachybocins E and F (5, 6), and stachybosides A and B (7, 8), and four known compounds (2, 9–11), were isolated from the sponge-derived fungus Stachybotrys chartarum MXH-X73. Their structures were determined by detailed analysis of spectroscopic data. The absolute configurations of 1–8 were determined by chemical hydrolysis and modified Mosher’s and Marfey’s methods. All compounds were tested in an anti-HIV activity assay, and compound 1 showed an inhibitory effect on HIV-1 replication by targeting reverse transcriptase. Further study exhibited that 1 could block NNRTIs-resistant strains (HIV-1RT-K103N, HIV-1RT-L100I,K103N, HIV-1RT-K103N,V108I, HIV-1RT-K103N,G190A, and HIV-1RT-K103N,P225H) as well as wild-type HIV-1 (HIV-1wt) with EC50 values of 7.0, 23.8, 13.3, 14.2, 6.2, and 8.4 μM, respectively.

Sorbicillamines A–E, Nitrogen-Containing Sorbicillinoids from the Deep-Sea-Derived Fungus Penicillium sp. F23–2

Co-reporter:Wenqiang Guo, Jixing Peng, Tianjiao Zhu, Qianqun Gu, Robert A. Keyzers, and Dehai Li

Journal of Natural Products 2013 Volume 76(Issue 11) pp:2106-2112

Publication Date(Web):November 11, 2013

DOI:10.1021/np4006647

Five new nitrogen-containing sorbicillinoids named sorbicillamines A–E (1–5) were isolated from an agitated culture of the deep-sea-derived fungus Penicillium sp. F23–2, which has previously produced indole alkaloids and terpenoids when cultured under static conditions. The structures of 1 to 5, including absolute configurations, were determined based on MS, NMR, and circular dichroism (CD) data. The cytotoxicities of the five new sorbicillin alkaloids against the HeLa, BEL-7402, HEK-293, HCT-116, and P388 cell lines were evaluated.

Aspulvinones from a mangrove rhizosphere soil-derived fungus Aspergillus terreus Gwq-48 with anti-influenza A viral (H1N1) activity

Co-reporter:Huquan Gao, Wenqiang Guo, Qiang Wang, Lianqing Zhang, Meilin Zhu, Tianjiao Zhu, Qianqun Gu, Wei Wang, Dehai Li

Bioorganic & Medicinal Chemistry Letters 2013 Volume 23(Issue 6) pp:1776-1778

Publication Date(Web):15 March 2013

DOI:10.1016/j.bmcl.2013.01.051

A new butenolide isoaspulvinone E (1), together with two known butenolides aspulvinone E (2) and pulvic acid (3) were isolated from the marine-derived fungus, Aspergillus terreus Gwq-48. They showed significant anti-influenza A H1N1 virus activities, with IC50 values of 32.3, 56.9, and 29.1 μg/mL, respectively. Moreover, only compound 1 exhibited effective inhibitory activity against H1N1 viral neuraminidase (NA), and docking of two isomers (1–2) into the active sites of NA showed that the E double bond Δ5(10) was essential to achieve activity.

Diorcinols B-E, new prenylated diphenyl ethers from the marine-derived fungus Aspergillus versicolor ZLN-60

Co-reporter:Huquan Gao, Lina Zhou, Shengxin Cai, Guojian Zhang, Tianjiao Zhu, Qianqun Gu and Dehai Li

The Journal of Antibiotics 2013 66(9) pp:539-542

Publication Date(Web):May 15, 2013

DOI:10.1038/ja.2013.40

Four new prenylated diphenyl ethers (1–4), diorcinols B-E, together with one known diorcinol (5), were obtained from the marine-derived fungus Aspergillus versicolor. Their structures were established on the basis of chemical and spectroscopic data. The absolute configurations of compounds 1 and 2 were determined by Mosher’s ester and specific rotation analysis. Their cytotoxicities were evaluated using A-549, Hela, BEL-7402 and K562 cell lines. Compound 3 exhibited moderate cytotoxicities against the Hela and K562 cell lines with the IC50 values of 31.5 and 48.9 μM, respectively, and compound 4 exhibited moderate cytotoxicity only against the Hela cell line with the IC50 value of 36.5 μM.

Hybrid Isoprenoids from a Reeds Rhizosphere Soil Derived Actinomycete Streptomyces sp. CHQ-64

Co-reporter:Qian Che, Tianjiao Zhu, Xin Qi, Attila Mándi, Tibor Kurtán, Xiaomei Mo, Jing Li, Qianqun Gu, and Dehai Li

Organic Letters 2012 Volume 14(Issue 13) pp:3438-3441

Publication Date(Web):June 15, 2012

DOI:10.1021/ol301396h

Indotertine A (1), a hybrid isoprenoid with a condensed pentacyclic skeleton, together with two related hybrid isoprenoids, drimentines F (2) and G (3), were isolated from a reeds rhizosphere soil derived actinomycete Streptomyces sp. CHQ-64. Their structures including absolute configurations were elucidated by spectroscopic methods, X-ray single crystal diffraction analysis, and TDDFT ECD calculations. Drimentines G (3) showed strong cytotoxicity against human cancer cells lines with IC50's down to 1.01 μM, while 1 and 2 showed no significant activity.

Diketopiperazine alkaloids from a mangrove rhizosphere soil derived fungus Aspergillus effuses H1-1

Co-reporter:Huquan Gao, Weizhong Liu, Tianjiao Zhu, Xiaomei Mo, Attila Mándi, Tibor Kurtán, Jing Li, Jing Ai, Qianqun Gu and Dehai Li

Organic & Biomolecular Chemistry 2012 vol. 10(Issue 47) pp:9501-9506

Publication Date(Web):12 Oct 2012

DOI:10.1039/C2OB26757H

Effusin A (1), a spirobicyclic N,O-acetal derivative with an unprecedented 3′,3a′,5′,6′-tetrahydrospiro[piperazine-2,2′-pyrano[2,3,4-de]chromene] ring system, and a spiro-polyketide-diketopiperazine hybrid dihydrocryptoechinulin D (2) were isolated from a mangrove rhizosphere soil derived fungus, Aspergillus effuses H1-1. Their structures were determined by detailed spectroscopic analysis. Effusin A (1) and dihydrocryptoechinulin D (2) occurred as racemates, the enantiomers of which were separated and characterized by online HPLC-ECD analysis and their absolute configurations were determined by the solution TDDFT ECD calculation approach. The cytotoxic effects of 1 and 2 were preliminarily evaluated and 2 showed potent activity on P388 cells with an IC50 value of 1.83 μM. The target of racemic 2 was also investigated and the (12R,28S,31S)-2 enantiomer showed selectivity against topoisomerase I.

Aspergilazine A, a diketopiperazine dimer with a rare N-1 to C-6 linkage, from a marine-derived fungus Aspergillus taichungensis

Co-reporter:Shengxin Cai, Xianglan Kong, Wei Wang, Huinan Zhou, Tianjiao Zhu, Dehai Li, Qianqun Gu

Tetrahedron Letters 2012 Volume 53(Issue 21) pp:2615-2617

Publication Date(Web):23 May 2012

DOI:10.1016/j.tetlet.2012.03.043

A novel diketopiperazine (DKP) dimer, aspergilazine A (1), dimerized by two DKP units via a rare N-1 to C-6 linkage, was isolated from the marine-derived fungus Aspergillus taichungensis ZHN-7-07. The structure was determined by the combination of spectroscopic and Marfey’s methods. Biological evaluation indicated that aspergilazine A (1) had a weak activity against influenza A (H1N1) virus.

Sorbiterrin A, a novel sorbicillin derivative with cholinesterase inhibition activity from the marine-derived fungus Penicillium terrestre

Co-reporter:Li Chen, Tianjiao Zhu, Yuanqing Ding, Ikhlas A. Khan, Qianqun Gu, Dehai Li

Tetrahedron Letters 2012 Volume 53(Issue 3) pp:325-328

Publication Date(Web):18 January 2012

DOI:10.1016/j.tetlet.2011.11.038

A novel sorbicillinoid named sorbiterrin A (1), possessing an unprecedented skeleton was isolated from a marine sediment derived fungus Penicillium terrestre. The structure including absolute stereochemistries was elucidated by analysis of NMR, MS data and TDDFT CD calculations. Sorbiterrin A showed moderate acetylcholinesterase (AChE) inhibitory effect with IC50 25 μg/mL.

Pyronepolyene C-glucosides with NF-κB inhibitory and anti-influenza A viral (H1N1) activities from the sponge-associated fungus Epicoccum sp. JJY40

Co-reporter:Jixing Peng, Jieying Jiao, Jing Li, Wei Wang, Qianqun Gu, Tianjiao Zhu, Dehai Li

Bioorganic & Medicinal Chemistry Letters 2012 Volume 22(Issue 9) pp:3188-3190

Publication Date(Web):1 May 2012

DOI:10.1016/j.bmcl.2012.03.044

A new pyronepolyene C-glucoside, named iso-D8646-2-6 (1) together with the known related compound D8646-2-6 (2), was isolated from the sponge-associated fungus Epicoccum sp. JJY40. They showed NF-κB inhibitory and anti-influenza A viral (H1N1) activities.

Penilactones A and B, two novel polyketides from Antarctic deep-sea derived fungus Penicillium crustosum PRB-2

Co-reporter:Guangwei Wu, Hongyan Ma, Tianjiao Zhu, Jing Li, Qianqun Gu, Dehai Li

Tetrahedron 2012 68(47) pp: 9745-9749

Publication Date(Web):

DOI:10.1016/j.tet.2012.09.038

Prenylated Polyhydroxy-p-terphenyls from Aspergillus taichungensis ZHN-7-07

Co-reporter:Shengxin Cai, Shiwei Sun, Huinan Zhou, Xianglan Kong, Tianjiao Zhu, Dehai Li, and Qianqun Gu

Journal of Natural Products 2011 Volume 74(Issue 5) pp:1106-1110

Publication Date(Web):April 12, 2011

DOI:10.1021/np2000478

Six new prenylated polyhydroxy-p-terphenyl metabolites, named prenylterphenyllins A−C (1−3) and prenylcandidusins A−C (5−7), and one new polyhydroxy-p-terphenyl with a simple tricyclic C-18 skeleton, named 4′′-dehydro-3-hydroxyterphenyllin (4), were obtained together with eight known analogues (8−15) from Aspergillus taichungensis ZHN-7-07, a root soil fungus isolated from the mangrove plant Acrostichum aureum. Their structures were determined by spectroscopic methods, and their cytotoxicity was evaluated using HL-60, A-549, and P-388 cell lines. Compounds 1 and 8 exhibited moderate activities against all three cell lines (IC50 1.53−10.90 μM), whereas compounds 4 and 6 displayed moderate activities only against the P-388 cell line (IC50 of 2.70 and 1.57 μM, respectively).

Two New Cyclic Pentapeptides from the Marine-Derived Fungus Aspergillus versicolor

Co-reporter:Li-Na Zhou;Hu-Quan Gao;Sheng-Xin Cai;Tian-Jiao Zhu;Qian-Qun Gu ;De-Hai Li

Helvetica Chimica Acta 2011 Volume 94( Issue 6) pp:1065-1070

Publication Date(Web):

DOI:10.1002/hlca.201000408

Abstract

Two new cyclic pentapeptides, named versicotides A (1) and B (2), were obtained from a marine-derived fungus strain ZLN-60, identified as Aspergillus versicolor. Their structures were established on the basis of chemical and spectroscopic evidence. Versicotides are new cyclic pentapeptides which contain an L-alanine residue, two anthranilic acid (=2-aminobenzoic acid) residues, and two N-methyl-L-alanine residues. Antitumor activities were evaluated by the SRB and MTT methods.

Two New 23-Membered Macrolactones from a Terrestrial Bacterium, Streptomyces sp. IMBJ01

Co-reporter:Jing-Yan Gu;Wen-Jun Han;Fang-Fang Qi;Jing Li;Shi-Wei Sun;Tian-Jiao Zhu;Wen-Jun Mao;Qian-Qun Gu;De-Hai Li

Helvetica Chimica Acta 2011 Volume 94( Issue 8) pp:1448-1453

Publication Date(Web):

DOI:10.1002/hlca.201000467

Abstract

Two new unusual 23-membered macrolactones, named griseoviridins B (1) and C (2), along with the known analogue griseoviridin (3) were isolated from the culture of Streptomyces sp. IMBJ01, a terrestrial bacterium isolated from Wolong, Sichuan Province, China. The structures of 1 and 2 were elucidated on the basis of extensive spectroscopic data and their absolute configurations were determined by comparison of their CD spectra with those of compound 3.

Antiviral isoindolone derivatives from an endophytic fungus Emericella sp. associated with Aegiceras corniculatum

Co-reporter:Guojian Zhang, Shiwei Sun, Tianjiao Zhu, Zhenjian Lin, Jingyan Gu, Dehai Li, Qianqun Gu

Phytochemistry 2011 Volume 72(11–12) pp:1436-1442

Publication Date(Web):August 2011

DOI:10.1016/j.phytochem.2011.04.014

Chemical investigation of the endophytic fungus Emericella sp. (HK-ZJ) isolated from the mangrove plant Aegiceras corniculatum led to isolation of six isoindolones derivatives termed as emerimidine A and B and emeriphenolicins A and D, and six previously reported compounds named aspernidine A and B, austin, austinol, dehydroaustin, and acetoxydehydroaustin, respectively. Their structures were elucidated on the basis of NMR spectroscopic evidence while the anti-influenza A viral (H1N1) activities of eight compounds were also evaluated using the cytopathic effect (CPE) inhibition assay.Graphical abstractIsoindolone derivatives (1–8), were produced by the endophytic fungus Emericella sp. Compounds 1 and 2 showed moderate antiviral activity against influenza A virus (H1N1).Highlights► Bioactive constituents from an endophytic fungus Emericella sp. were investigated. ► Six isoindolone derivatives and six known compounds were obtained. ► Two compounds showed moderate antiviral activity.

Sterigmatocystins from the deep-sea-derived fungus Aspergillus versicolor

Co-reporter:Shengxin Cai, Tianjiao Zhu, Lin Du, Boyu Zhao, Dehai Li and Qianqun Gu

The Journal of Antibiotics 2011 64(2) pp:193-196

Publication Date(Web):December 1, 2010

DOI:10.1038/ja.2010.154

Three new sterigmatocystin derivatives, oxisterigmatocystin A (1), oxisterigmatocystin B (2) and oxisterigmatocystin C (3), together with one known compound, 5-methoxysterigmatocystin (4), were isolated from the deep-sea-derived fungus Aspergillus versicolor. The structures of the new compounds were elucidated by spectroscopic methods. The cytotoxicities of compounds 1–4 were evaluated against the A-549 and HL-60 cell lines. Compound 4 exhibited moderate cytotoxicities against the A-549 and HL-60 cell lines with IC50 value of 3.86 and 5.32 μM, respectively.

Three New Indole-Containing Diketopiperazine Alkaloids from a Deep-Ocean Sediment Derived Fungus Penicillium griseofulvum

Co-reporter:Li-Na Zhou;Tian-Jiao Zhu;Sheng-Xin Cai;Qian-Qun Gu ;De-Hai Li

Helvetica Chimica Acta 2010 Volume 93( Issue 9) pp:1758-1763

Publication Date(Web):

DOI:10.1002/hlca.200900443

Abstract

Three new indole-containing diketopiperazine alkaloids, named variecolorins M–O (1–3), together with the eight known analogues 4–11, were isolated from a deep-ocean sediment-derived fungus, Penicillium griseofulvum. Their structures were determined by analysis of the spectroscopic data. The 2,2-diphenyl-1-picrylhydrazinyl (DPPH) radical-scavenging activities and the cell-proliferation inhibitory activities of the three new compounds 1–3 were investigated.

Advanced tools in marine natural drug discovery

Co-reporter:Guojian Zhang, Jing Li, Tianjiao Zhu, Qianqun Gu, Dehai Li

Current Opinion in Biotechnology (December 2016) Volume 42() pp:13-23

Publication Date(Web):1 December 2016

DOI:10.1016/j.copbio.2016.02.021

•Marine natural products have been proved to be promising drug sources.•New tools make the utility of “dark matter” possible.•Current developed dereplication strategies highly increase the chance of finding new bioactive structures.•The function of marine natural products can profit from high-content/throughput screening.Marine natural products (MNPs) remain promising drug sources with several marine-derived drugs having been successfully approved. Nevertheless, it is never a smooth sailing to seek bioactive compounds from marine environments, during which many challenges are need to be faced to, for example, discovering unique marine resources, reviving unculturable organisms outside the marine environment, distinguishing novel compounds from the known ones, and disclosing the function of MNPs and optimizing their pharmacological use. Herein we review some advanced techniques and methodologies that can be employed to deal with above challenges with the intent of inspiring the forthcoming efforts in MNPs discovery pipelines.Download high-res image (138KB)Download full-size image

Antiviral Alkaloids Produced by the Mangrove-Derived Fungus Cladosporium sp. PJX-41

Co-reporter:Jixing Peng ; Tao Lin ; Wei Wang ; Zhihong Xin ; Tianjiao Zhu ; Qianqun Gu

Journal of Natural Products () pp:

Publication Date(Web):June 12, 2013

DOI:10.1021/np400200k

Six new indole alkaloids including five new glyantrypine derivatives (1, 2a, 2b, 3, 4) and a new pyrazinoquinazoline derivative (5), together with eight known alkaloids (6–13), were isolated from the culture of the mangrove-derived fungus Cladosporium sp. PJX-41. Their structures were elucidated primarily by spectroscopic and physical data. The absolute configurations of compounds 1–9 were established on the basis of CD, NOESY data, and single-crystal X-ray diffraction analysis. Compounds 2b, 5, 7–9, and 11 exhibited significant activities against influenza virus A (H1N1), with IC50 values of 82–89 μM.

Diketopiperazine alkaloids from a mangrove rhizosphere soil derived fungus Aspergillus effuses H1-1

Co-reporter:Huquan Gao, Weizhong Liu, Tianjiao Zhu, Xiaomei Mo, Attila Mándi, Tibor Kurtán, Jing Li, Jing Ai, Qianqun Gu and Dehai Li

Organic & Biomolecular Chemistry 2012 - vol. 10(Issue 47) pp:NaN9506-9506

Publication Date(Web):2012/10/12

DOI:10.1039/C2OB26757H