Hiroyuki Morita

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Organization: University of Toyama

Department: Institute of Natural Medicine

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Chemicals
References

Prenylation of a Nonaromatic Carbon of Indolylbutenone by a Fungal Indole Prenyltransferase

Co-reporter:Jing Chen, Hiroyuki Morita, Toshiyuki Wakimoto, Takahiro Mori, Hiroshi Noguchi, and Ikuro Abe

Organic Letters June 15, 2012 Volume 14(Issue 12) pp:3080-3083

Publication Date(Web):June 15, 2012

DOI:10.1021/ol301129x

FtmPT1 from Aspergillus fumigatus is a fungal indole prenyltransferase (PT) that normally catalyzes the regiospecific prenylation of brevianamide F (cyclo-l-Trp-l-Pro) at the C-2 position of the indole ring with dimethylallyl diphosphate (DMAPP). Interestingly, FtmPT1 exhibited remarkable substrate tolerance and accepted (E)-4-(1H-indol-3-yl)but-3-en-2-one (1) as a substrate to produce an unnatural novel α-prenylindolylbutenone (1a). This is the first demonstration of the prenylation of a nonaromatic carbon of the acceptor substrate by a fungal indole PT.

New merosesquiterpenes from a Vietnamese marine sponge of Spongia sp. and their biological activities

Co-reporter:Hien Minh Nguyen, Takuya Ito, Shin-ichiro Kurimoto, Mika Ogawa, Nwet Nwet Win, Vo Quoc Hung, Hoai Thi Nguyen, Takaaki Kubota, Jun'ichi Kobayashi, Hiroyuki Morita

Bioorganic & Medicinal Chemistry Letters 2017 Volume 27, Issue 14(Issue 14) pp:

Publication Date(Web):15 July 2017

DOI:10.1016/j.bmcl.2017.05.060

The investigation of the Vietnamese marine sponge Spongia sp. led to the isolation of three new sesquiterpene phenols, langconols A–C (1–3), and one new sesquiterpene hydroxyquinone, langcoquinone C (4), together with two known meroterpenoids (5 and 6). Their structures were determined on the basis of spectroscopic analyses and comparisons with published data. Furthermore, the antibacterial assays of the isolates 1–6 suggested that 4 and 6 had significant antibacterial activities against Bacillus subtilis and Staphylococcus aureus, with MICs ranging from 6.25 to 25.0 µM, while 1 and 3 possessed significant antibacterial activities against B. subtilis with MICs of 12.5 and 25.0 µM, respectively. In contrast, cytotoxic assays of the isolated compounds 1–6, as well as compounds 7–15 previously isolated from this sponge, indicated that 1 and the previously reported anti-B. subtilis and anti-S. aureus sesquiterpene phenol 9 lacked cytotoxic activities against three human cancer cell lines (A549, lung cancer; MCF7, breast cancer; HeLa, cervix cancer) and a human normal cell line (WI-38 fibroblast).Download high-res image (146KB)Download full-size image

Syntheses of benzophenone-xanthone hybrid polyketides and their antibacterial activities

Co-reporter:Takeshi Kodama, Takuya Ito, Dya Fita Dibwe, So-Yeun Woo, Hiroyuki Morita

Bioorganic & Medicinal Chemistry Letters 2017 Volume 27, Issue 11(Issue 11) pp:

Publication Date(Web):1 June 2017

DOI:10.1016/j.bmcl.2017.04.017

Muchimangins are benzophenone-xanthone hybrid polyketides produced by Securidaca longepedunculata. However, their biological activities have not been fully investigated, since they are minor constituents in this plant. To evaluate the possibility of muchimangins as antibacterial agent candidates, five muchimangin analogs were synthesized from 2,4,5-trimethoxydiphenyl methanol and the corresponding xanthones, by utilizing p-toluenesulfonic acid monohydrate for the Brønsted acid-catalysis. The antibacterial assays against Gram-positive bacteria, Staphylococcus aureus and Bacillus subtilis, and Gram-negative bacteria, Klebsiella pneumoniae and Escherichia coli, revealed that the muchimangin analogs (±)-1,3,6,8-tetrahydroxy-4-(phenyl-(2′,4′,5′-trimethoxyphenyl)methyl)-xanthone (1), (±)-1,3,6-trihydroxy-4-(phenyl-(2′,4′,5′-trimethoxyphenyl)methyl)-xanthone (2), and (±)-1,3-dihydroxy-4-(phenyl-(2′,4′,5′-trimethoxyphenyl)methyl)-xanthone (3) showed significant activities against S. aureus, with MIC values of 10.0, 10.0, and 25.0 μM, respectively. Analogs (±)-1 and (±)-2 also exhibited antibacterial activities against B. subtilis, with MIC values of 50.0 and 12.5 μM, respectively. Furthermore, (+)-3 enhanced the antibacterial activity against S. aureus, with a MIC value of 10 μM.Download high-res image (62KB)Download full-size image

Labdane diterpenoids from Curcuma amada rhizomes collected in Myanmar and their antiproliferative activities

Co-reporter:Nwet Nwet Win, Takuya Ito, Hla Ngwe, Yi Yi Win, Prema, Yasuko Okamoto, Masami Tanaka, Yoshinori Asakawa, Ikuro Abe, Hiroyuki Morita

Fitoterapia 2017 Volume 122(Volume 122) pp:

Publication Date(Web):1 October 2017

DOI:10.1016/j.fitote.2017.08.006

Four new labdane diterpenoids, 12β-hydroxy-15-norlabda-8(17),13(14)-dien-16-oic acid (1), (E)-15-ethoxy-15-methoxylabda-8(17),12-dien-16-al (2), (E)-15α-ethoxy-14α-hydroxylabda-8(17),12-dien-16-olide (3), and 15-ethoxy-12β-hydroxylabda-8(17),13(14)-dien-16,15-olide (4) were isolated from the methanol extract of Curcuma amada rhizomes collected in Myanmar, together with 13 known analogs. Their structures were elucidated by extensive spectroscopic techniques. All of the isolates were evaluated for their antiproliferative activities against a small panel of five different human cancer cell lines (A549, human lung cancer; HeLa, human cervical cancer; MCF7, human breast cancer; PANC-1 and PSN-1, human pancreatic cancer). Among the isolates, compounds 2 − 4, 7, 8, 12, and 17 showed mild antiproliferative activities with IC50 values ranging from 19.7 to 96.1 μM. (E)-14-Hydroxy-15-norlabda-8(17),12-dien-16-al (11) exhibited strong antiproliferative activities selectively against HeLa, PANC-1, and PSN-1 cells, with IC50 values of 5.88, 1.00, and 3.98 μM, respectively. These potencies were comparable to those of the positive control, 5-fluorouracil.Download high-res image (159KB)Download full-size image

New sesquiterpene lactones, vernonilides A and B, from the seeds of Vernonia anthelmintica in Uyghur and their antiproliferative activities

Co-reporter:Takuya Ito, Simayijiang Aimaiti, Nwet Nwet Win, Takeshi Kodama, Hiroyuki Morita

Bioorganic & Medicinal Chemistry Letters 2016 Volume 26(Issue 15) pp:3608-3611

Publication Date(Web):1 August 2016

DOI:10.1016/j.bmcl.2016.06.009

A new guaianolide sesquiterpene lactone, vernonilide A (1), and a new elemanolide sesquiterpene lactone, vernonilide B (2), were isolated from the seeds of Vernonia anthelmintica, together with three known elemanolide sesquiterpene lactones (3–5). The structures of the isolated compounds were elucidated on the basis of physicochemical evidences. Compounds 1, 3, and 4 showed strong antiproliferative activities against three human cancer cell lines (A549, HeLa, and MDA-MB-231), with IC50 values ranging from 0.10 to 1.00 μM. In addition, 5 exhibited significant antiproliferative activities against HeLa and MDA-MB-231 cells, with IC50 values ranging from 1.90 to 2.20 μM. The antiproliferative activities of the acetyl derivatives 6 and 7 prepared from 4 and 3, respectively, against the three cell lines were 4–10-fold weaker than the original activities.

Quassinoids: Viral protein R inhibitors from Picrasma javanica bark collected in Myanmar for HIV infection

Co-reporter:Nwet Nwet Win, Takuya Ito, Yi Yi Win, Hla Ngwe, Takeshi Kodama, Ikuro Abe, Hiroyuki Morita

Bioorganic & Medicinal Chemistry Letters 2016 Volume 26(Issue 19) pp:4620-4624

Publication Date(Web):1 October 2016

DOI:10.1016/j.bmcl.2016.08.055

Viral protein R (Vpr) is an accessory protein that plays important roles in the viral pathogenesis of Human Immunodeficiency Virus-1 (HIV-1). An assay for anti-Vpr activity, using TREx-HeLa-Vpr cells, is a promising strategy to discover Vpr inhibitors. The anti-Vpr assay revealed that the CHCl3-soluble extract of Picrasma javanica bark possesses potent anti-Vpr activity. Furthermore, studies of quassinoids (1–15) previously isolated from the extract demonstrated that all of the tested quassinoids exhibit anti-Vpr activity. Among the tested compounds, javanicin I (15) exhibited the most potent anti-Vpr activity (***p <0.001) in comparing with that of the positive control, damnacanthal. The structure–activity relationships of the active quassinoids suggested that the presence of a methyl group at C-13 in the 2,12,14-triene-1,11,16-trione-2,12-dimethoxy-18-norpicrasane quassinoids is the important factor for the potent inhibitory effect in TREx-HeLa-Vpr cells.

New antibacterial sesquiterpene aminoquinones from a Vietnamese marine sponge of Spongia sp.

Co-reporter:Hien Minh Nguyen, Takuya Ito, Nwet Nwet Win, Takeshi Kodama, Vo Quoc Hung, Hoai Thi Nguyen, Hiroyuki Morita

Phytochemistry Letters 2016 Volume 17() pp:288-292

Publication Date(Web):September 2016

DOI:10.1016/j.phytol.2016.08.012

⿢The bioassay-guided separation of Spongia sp. was performed.⿢Nine meroterpenoids including two new sesquiterpene aminoquinones were isolated.⿢The isolated compounds were tested for antibacterial activity.⿢The new and five known compounds had significant antibacterial activities against Bacillus subtilis and Staphylococcus aureus.Two new sesquiterpene aminoquinones, langcoquinones A (1) and B (2), together with seven known meroterpenoids (3⿿9), were isolated from the marine sponge Spongia sp. collected in Vietnam. Their structures were determined on the basis of spectroscopic analyses and comparisons with published data. The antibacterial activities of the isolated compounds (1⿿9) were investigated against four bacterial strains. Among these, the new sesquiterpene aminoquinones (1 and 2) and the known related compounds (3, 5, 6, 8, and 9) exhibited significant antibacterial activities against Staphylococcus aureus and Bacillus subtilis, with MICs ranging from 6.25 to 12.5 μM.

New acylphloroglucinol derivatives from the leaves of Baeckea frutescens

Co-reporter:Khoirun Nisa, Takuya Ito, Subehan, Takashi Matsui, Takeshi Kodama, Hiroyuki Morita

Phytochemistry Letters 2016 15() pp: 42-45

Publication Date(Web):March 2016

DOI:10.1016/j.phytol.2015.11.011

A new cycloartane-type triterpene and a new eicosanoic acid ester from fruits of Paullinia pinnata L.

Co-reporter:Maurice D. Awouafack, Takuya Ito, Pierre Tane, Takeshi Kodama, Masami Tanaka, Yoshinori Asakawa, Hiroyuki Morita

Phytochemistry Letters 2016 15() pp: 220-224

Publication Date(Web):March 2016

DOI:10.1016/j.phytol.2016.02.002

Picrajavanicins H–M, new quassinoids from Picrasma javanica collected in Myanmar and their antiproliferative activities

Co-reporter:Nwet Nwet Win, Takuya Ito, Ismail, Takeshi Kodama, Yi Yi Win, Masami Tanaka, Yasuko Okamoto, Hiroshi Imagawa, Hla Ngwe, Yoshinori Asakawa, Ikuro Abe, Hiroyuki Morita

Tetrahedron 2016 Volume 72(Issue 5) pp:746-752

Publication Date(Web):4 February 2016

DOI:10.1016/j.tet.2015.12.030

Six new tetracyclic quassinoids, picrajavanicins H–M, along with two known analogues were isolated from the CHCl3 soluble extract of Picrasma javanica bark collected in Myanmar. The structures of these compounds were elucidated using spectroscopic techniques, including 1D and 2D NMR. The absolute configuration at C-4 of picrajavanicin L was determined to be R by the modified Mosher method. In contrast, the absolute structures of picrajavanicin H and picrasin A were determined by the X-ray diffraction analyses. The antiproliferative activities of the isolated compounds were evaluated against a panel of five different human cancer cell lines. All isolates exhibited potent and selective antiproliferative activities against human pancreatic cancer PANC-1 cells, with IC50 values ranging from 3.25 to 17.41 μM.

Structural Basis for β-Carboline Alkaloid Production by the Microbial Homodimeric Enzyme McbB

Co-reporter:Takahiro Mori, Shotaro Hoshino, Shusaku Sahashi, Toshiyuki Wakimoto, Takashi Matsui, Hiroyuki Morita, Ikuro Abe

Chemistry & Biology 2015 Volume 22(Issue 7) pp:898-906

Publication Date(Web):23 July 2015

DOI:10.1016/j.chembiol.2015.06.006

•Structure of McbB complexed with substrate is reported at a resolution of 2.48 Å•McbB has a novel protein folding which is totally different from the other enzymes•McbB employs a similar mechanism to that of the plant strictosidine synthase•Site-directed mutagenesis expanded the substrate scope of McbB enzyme reactionThe β-carboline (βC) alkaloids occur throughout nature and exhibit diverse biological activities. In contrast to βC alkaloid synthesis in plants, the biosynthesis in microorganisms remains poorly understood. The recently reported McbB from Marinactinospora thermotolerans is a novel enzyme proposed to catalyze the Pictet-Spengler (PS) reaction of L-tryptophan and oxaloacetaldehyde to produce the βC scaffold of marinacarbolines. In this study, we solved the crystal structure of McbB complexed with L-tryptophan at 2.48 Å resolution, which revealed the novel protein folding of McbB and the totally different structure from those of other PS condensation catalyzing enzymes, such as strictosidine synthase and norcoclaurine synthase from plants. Structural analysis and site-directed mutagenesis confirmed that the previously proposed catalytic Glu97 at the active-site center functions as an acid and base catalyst. Remarkably, the structure-based mutants R72A and H87A, with expanded active-site cavities, newly accepted bulky phenylglyoxal as the aldehyde substrate, to produce 1-benzoyl-3-carboxy-β-carboline.Figure optionsDownload full-size imageDownload high-quality image (239 K)Download as PowerPoint slide

Picrajavanicins A–G, Quassinoids from Picrasma javanica Collected in Myanmar

Co-reporter:Nwet Nwet Win; Takuya Ito; Ismail; Takeshi Kodama; Yi Yi Win; Masami Tanaka; Hla Ngwe; Yoshinori Asakawa; Ikuro Abe

Journal of Natural Products 2015 Volume 78(Issue 12) pp:3024-3030

Publication Date(Web):November 25, 2015

DOI:10.1021/acs.jnatprod.5b00824

Seven new tetracyclic quassinoids, picrajavanicins A–G (1–7), along with three known analogues, were isolated from a CHCl3-soluble extract of the bark of Picrasma javanica collected in Myanmar. The structures of these compounds were elucidated using spectroscopic techniques, including 1D and 2D NMR. The absolute configuration at C-2 of 2 was determined to be S by the modified Mosher method. All the isolates were tested for their antiproliferative activities against a small panel of five human cancer cell lines. However, none of the isolated compounds exhibited inhibitory activity against any of the cancer cells used (IC50 values >10 μM).

Kaempulchraols P–T, Diterpenoids from Kaempferia pulchra Rhizomes Collected in Myanmar

Co-reporter:Nwet Nwet Win; Takuya Ito; Simayijiang Aimaiti; Takeshi Kodama; Masami Tanaka; Hla Ngwe; Yoshinori Asakawa; Ikuro Abe

Journal of Natural Products 2015 Volume 78(Issue 9) pp:2306-2309

Publication Date(Web):September 3, 2015

DOI:10.1021/acs.jnatprod.5b00523

The isolation of the oily fraction obtained from the CHCl3-soluble extract of the rhizomes of Kaempferia pulchra afforded five new isopimarane diterpenoids, kaempulchraols P–T (1–5), along with two known analogues. The structures were elucidated using spectroscopic techniques, including 2D NMR spectroscopy.

Kaempulchraols A–H, Diterpenoids from the Rhizomes of Kaempferia pulchra Collected in Myanmar

Co-reporter:Nwet Nwet Win; Takuya Ito; Simayijiang Aimaiti; Hiroshi Imagawa; Hla Ngwe; Ikuro Abe

Journal of Natural Products 2015 Volume 78(Issue 5) pp:1113-1118

Publication Date(Web):April 28, 2015

DOI:10.1021/acs.jnatprod.5b00108

Eight new diterpenoids, kaempulchraols A–H (1–8), along with five known analogues were isolated from the CHCl3-soluble extract of rhizomes of Kaempferia pulchra of Myanmar. The structures of these compounds were elucidated using extensive spectroscopic techniques including X-ray diffraction analysis. All the isolates were tested for their antiproliferative activity against a panel of five human cancer cell lines (A549, human lung cancer; HeLa, human cervix cancer; PANC-1 and PSN-1, human pancreatic cancer; MDA-MB-231, human breast cancer) and TIG-3, normal human primary fibroblast cells. Kaempulchraol F (6) exhibited weak activity against the human pancreatic PSN-1 cell line with an IC50 value of 12.3 μM.

A new polyoxygenated cyclohexene and a new megastigmane glycoside from Uvaria grandiflora

Co-reporter:Duc Viet Ho, Takeshi Kodama, Hien Thi Bich Le, Kiem Van Phan, Thao Thi Do, Tai Huu Bui, Anh Tuan Le, Nwet Nwet Win, Hiroshi Imagawa, Takuya Ito, Hiroyuki Morita, Hoai Thi Nguyen

Bioorganic & Medicinal Chemistry Letters 2015 Volume 25(Issue 16) pp:3246-3250

Publication Date(Web):15 August 2015

DOI:10.1016/j.bmcl.2015.05.066

A new polyoxygenated cyclohexene, (−)-3-O-debenzoylzeylenone (1), and a new megastigmane glycoside, grandionoside A (2), were isolated from the aerial parts of Uvaria grandiflora collected in Vietnam, together with ten known compounds including polyoxygenated cyclohexenes (3–6), a triterpenoid (7), an alkaloid (8), a long chain alcohol (9), hexenyl glycopyranoside (10), and saponins (11–12). Their chemical structures were elucidated by a combination of extensive NMR spectroscopy with X-ray crystallographic analysis for 1, and chemical conversion for 2. Compound 1 exhibited significant cytotoxicity against the LU-1 and SK-Mel-2 cell lines with IC50 values of 4.68 and 3.63 μM, respectively. Remarkably, the cytotoxicity of 12 against the LU-1, KB, Hep-G2, MKN-7, and SW-480 cell lines was comparable to that of ellipticine, the positive control, with IC50 values ranging from 1.24 to 1.60 μM.

Kaempulchraols I–O: new isopimarane diterpenoids from Kaempferia pulchra rhizomes collected in Myanmar and their antiproliferative activity

Co-reporter:Nwet Nwet Win, Takuya Ito, Simayijiang Aimaiti, Takeshi Kodama, Hiroshi Imagawa, Hla Ngwe, Yoshinori Asakawa, Ikuro Abe, Hiroyuki Morita

Tetrahedron 2015 Volume 71(Issue 29) pp:4707-4713

Publication Date(Web):22 July 2015

DOI:10.1016/j.tet.2015.05.075

The isolation of the CHCl3 soluble extract of Kaempferia pulchra rhizomes afforded seven new isopimarane diterpenoids, kaempulchraols I–O, together with one known analog. The structures of these compounds were elucidated using 1D and 2D NMR and X-ray diffraction analyses. The antiproliferative activity of the isolated compounds was evaluated against a panel of five human cancer cell lines. Kaempulchraol L exhibited weak antiproliferative activity against PANC-1 and PSN-1 cells with IC50 values of 39.9 and 22.6 μM, respectively.

Expression, purification and crystallization of a plant polyketide cyclase from Cannabis sativa

Co-reporter:Xinmei Yang;Takashi Matsui;Takahiro Mori;Futoshi Taura;Hiroshi Noguchi;Ikuro Abe

Acta Crystallographica Section F 2015 Volume 71( Issue 12) pp:1470-1474

Publication Date(Web):

DOI:10.1107/S2053230X15020385

Plant polyketides are a structurally diverse family of natural products. In the biosynthesis of plant polyketides, the construction of the carbocyclic scaffold is a key step in diversifying the polyketide structure. Olivetolic acid cyclase (OAC) from Cannabis sativa L. is the only known plant polyketide cyclase that catalyzes the C2–C7 intramolecular aldol cyclization of linear pentyl tetra-β-ketide-CoA to generate olivetolic acid in the biosynthesis of cannabinoids. The enzyme is also thought to belong to the dimeric α+β barrel (DABB) protein family. However, because of a lack of functional analysis of other plant DABB proteins and low sequence identity with the functionally distinct bacterial DABB proteins, the catalytic mechanism of OAC has remained unclear. To clarify the intimate catalytic mechanism of OAC, the enzyme was overexpressed in Escherichia coli and crystallized using the vapour-diffusion method. The crystals diffracted X-rays to 1.40 Å resolution and belonged to space group P3₁21 or P3₂21, with unit-cell parameters a = b = 47.3, c = 176.0 Å. Further crystallographic analysis will provide valuable insights into the structure–function relationship and catalytic mechanism of OAC.

Expression, purification and crystallization of a fungal type III polyketide synthase that produces the csypyrones

Co-reporter:Dengfeng Yang;Takahiro Mori;Takashi Matsui;Makoto Hashimoto, ;Isao Fujii ;Ikuro Abe

Acta Crystallographica Section F 2014 Volume 70( Issue 6) pp:730-733

Publication Date(Web):

DOI:10.1107/S2053230X14008516

CsyB from Aspergillus oryzae is a novel type III polyketide synthase that catalyzes the formation of csypyrone B1 [4-(3-acetyl-4-hydroxy-2-oxo-2H-pyran-6-yl)butyric acid] from fatty acyl-CoA, malonyl-CoA and acetoacetyl-CoA. Recombinant CsyB expressed in Escherichia coli was crystallized by the sitting-drop vapour-diffusion method. The crystals belonged to space P2₁, with unit-cell parameters a = 70.0, b = 104.8, c = 73.5 Å, β = 114.4°.

Prenylation of a Nonaromatic Carbon of Indolylbutenone by a Fungal Indole Prenyltransferase

Co-reporter:Jing Chen, Hiroyuki Morita, Toshiyuki Wakimoto, Takahiro Mori, Hiroshi Noguchi, and Ikuro Abe

Organic Letters 2012 Volume 14(Issue 12) pp:3080-3083

Publication Date(Web):2017-2-22

DOI:10.1021/ol301129x

Two new cyclopentenones and a new furanone from Baeckea frutescens and their cytotoxicities

Co-reporter:Takuya Ito, Khoirun Nisa, Takeshi Kodama, Masami Tanaka, Yasuko Okamoto, Ismail, Hiroyuki Morita

Fitoterapia (July 2016) Volume 112() pp:132-135

Publication Date(Web):1 July 2016

DOI:10.1016/j.fitote.2016.05.017

Two new cyclopentenones, frutescencenones A (1) and B (2), and a new furanone derivative, frutescencenone C (3), together with two known cyclopentenones (4 and 5), were isolated from the leaves of Baeckea frutescens. Their structures were deduced by comprehensive spectroscopic analyses, including 1D and 2D NMR, and HREIMS data. Frutescencenone A (1) showed moderate growth inhibitory activity against human lung A549, pancreatic PSN-1, and breast MDA-MB-231 cancer cell lines, with IC50 values of 36.3 μM, 38.2 μM, and 29.3 μM, respectively. In contrast, frutescencenone C (3) showed selective cytotoxic activity against PSN-1, with an IC50 value of 20.1 μM.Download high-res image (188KB)Download full-size image

New phloroglucinol derivatives from Indonesian Baeckea frutescens

Co-reporter:Takuya Ito, Khoirun Nisa, Senda Kartika Rakainsa, Sbehan Lallo, Hiroyuki Morita

Tetrahedron (23 February 2017) Volume 73(Issue 8) pp:

Publication Date(Web):23 February 2017

DOI:10.1016/j.tet.2017.01.016

Chemical investigation of the leaves of Baeckea frutescens (Myrtacea) led to the isolation and characterization of five new phloroglucinol derivatives, baeckenones G−K (1–5), together with two known compounds, ursolic acid (6) and humulene (7). The chemical structures were determined by extensive 1D- and 2D-NMR, and MS spectroscopic analyses. Baeckenones J (4) and K (5) exhibited antiproliferative activities against human lung A549 and pancreatic PSN-1 cancer cell lines, with IC50 values ranging from 11.8 to 19.2 μM.

Filamenting temperature-sensitive mutant Z inhibitors from Glycyrrhiza glabra and their inhibitory mode of action

Co-reporter:Takashi Matsui, Subehan Lallo, Khoirun Nisa, Hiroyuki Morita

Bioorganic & Medicinal Chemistry Letters (15 March 2017) Volume 27(Issue 6) pp:

Publication Date(Web):15 March 2017

DOI:10.1016/j.bmcl.2017.01.095

FtsZ is an essential protein for bacterial cell division, and an attractive and underexploited novel antibacterial target protein. Screening of Indonesian plants revealed the inhibitory activity of the methanol extract of Glycyrrhiza glabra on the Bacillus subtilis FtsZ (BsFtsZ) GTPase, and further bioassay-guided fractionation of the active methanol extract led to the isolation of seven known polyketides (1–7). Among them, gancaonin I (1), glycyrin (3), and isolicoflavanol (5) exhibited anti-BsFtsZ GTPase activities, at levels comparable to that of the synthetic FtsZ inhibitor, Zantrin Z3. Enzymatic assays using a BsFtsZ Val307R mutant protein and in silico simulations suggested that 1, 3, and 5 bind to the cleft on BsFtsZ, as in the case of the previously reported uncompetitive FtsZ inhibitor, PC190723, and thereby display their significant anti-BsFtsZ inhibitory activities. Furthermore, 1 also showed significant inhibitory activity against B. subtilis, with a MIC value of 5 μM. The present study provides new insights into the naturally occurring B. subtilis growth inhibitors.