Co-reporter:Zhi-Wei Zhang, Jia-Qiang Zhang, Ling Hui, Shi-Wu Chen, Xuan Tian
European Journal of Medicinal Chemistry 2010 Volume 45(Issue 4) pp:1673-1677
Publication Date(Web):April 2010
DOI:10.1016/j.ejmech.2009.12.032
Deoxypodophyllotoxin inhibits tubulin polymerization and induces cell cycle arrest at G2/M, followed by apoptosis. In order to find compounds with superior bioactivity and less toxicity, a series of spin-labeled derivatives of deoxypodophyllotoxin were synthesized by reacting 4′-demethyl-4-deoxypodophyllotoxin (DPPT) with N-(1-oxyl-2,2,6,6-tetramethyl-4-piperidinyloxycarbonyl) amino acids. The cytotoxic activities against three tumor cell lines (HL-60, RPMI-8226, A-549) in vitro and the antioxidative activities in tissues of Sprague Dawley (SD) rats of target compounds were evaluated, and the results indicated that compounds 11a–h were more potent in terms of cytotoxicities and antioxidative activities than either parent compound DPPT or anticancer drug VP-16.The spin-labeled derivatives of deoxypodophyllotoxin 11a–h showed higher potent cytotoxicities (HL-60, RPMI-8226 and A-549) and antioxidative activities than parent compound DPPT and anticancer drug VP-16.
Co-reporter:Jia-Qiang Zhang, Zhi-Wei Zhang, Ling Hui, Shi-Wu Chen, Xuan Tian
Bioorganic & Medicinal Chemistry Letters 2010 Volume 20(Issue 3) pp:983-986
Publication Date(Web):1 February 2010
DOI:10.1016/j.bmcl.2009.12.048
A series of novel spin-labeled podophyllotoxin derivatives were synthesized by reacting the corresponding N-(1-oxyl-2,2,6,6-tetramethyl-4-piperidinyloxy carbonyl)-amino acids with 4β-amino-4′-demethylepipodophyllotoxin. The synthesized derivatives 12a–g were evaluated for the partition coefficients, cytotoxicities in vitro against three tumor cell lines (A-549, HL-60, and RPMI-8226) and antioxidative activities in tissues of SD rats by the TBA method. The vast majority of target compounds have shown superior or comparable activities against A-549, HL-60, and RPMI-8226 compared to VP-16, and they have shown more significant antioxidative activities and superior water solubility than VP-16.The synthesized compounds showed superior or comparable cytotoxicities and pronounced antioxidative activity compared to VP-16.
Co-reporter:Shi-Wu Chen, Rong Xiang, Jian Liu, Xuan Tian
Bioorganic & Medicinal Chemistry 2009 Volume 17(Issue 8) pp:3111-3117
Publication Date(Web):15 April 2009
DOI:10.1016/j.bmc.2009.03.009
A series of novel conjugates of podophyllotoxin and 5-FU were designed using association strategy and were synthesized by coupling 4′-demethylepipodophyllotoxin with 5-FU-N1-alkyl amino acid ester. These derivatives have been evaluated for cytotoxicity in vitro against tumour cell lines (HL-60, K562, A-549 and AGS), and their octanol–water partition coefficients (log P) were also determined. As compared with VP-16, most compounds showed superior water solubility, as well as more potent inhibitions against these four tumour cell lines. Compound 21 showed interaction with calf thymus DNA, and it was relatively resistant to metabolism by human plasma.The novel conjugates 10–21 showed superior or comparable inhibitions against HL-60, K562, A-549 and AGS to VP-16, and better water solubility. Compound 21 also showed interaction with calf thymus DNA, and was stable in human plasma.
Co-reporter:Shi-Wu Chen, Yun-Hua Wang, Yan Jin, Xuan Tian, Yong-Tang Zheng, Du-Qiang Luo, Yong-Qiang Tu
Bioorganic & Medicinal Chemistry Letters 2007 Volume 17(Issue 7) pp:2091-2095
Publication Date(Web):1 April 2007
DOI:10.1016/j.bmcl.2006.11.070
In order to explore the range of biological activities of the podophyllotoxin compound class, a novel series of derivatives of podophyllotoxin, which were conjugates containing stavudine and different structural podophyllotoxin analogues, were designed, synthesized, and evaluated for their anti-HIV-1 activities in vitro. Among these compounds, 19d and 19c showed the highest anti-HIV-1 activities with EC50 values of 0.17 and 0.29 μM and TI values of 466.9 and 354.5, respectively.A novel series of derivatives of podophyllotoxin as anti-HIV-1 agents were synthesized, 19d and 19c showed the highest anti-HIV activity with EC50 values of 0.17 and 0.29 μM and TI values of 466.9 and 354.5, respectively.
Co-reporter:Yan Jin, Shi-Wu Chen, Xuan Tian
Bioorganic & Medicinal Chemistry 2006 Volume 14(Issue 9) pp:3062-3068
Publication Date(Web):1 May 2006
DOI:10.1016/j.bmc.2005.12.025
In order to find compounds with superior bioactivity and less toxicity, a series of spin-labeled podophyllotoxin derivatives were synthesized and tested for the partition coefficients and cytotoxicity against P-388 and A-549. Furthermore, we also determined antioxidant activities of target molecular in tissues of SD rats by the TBA method. Results revealed that most synthesized compounds showed more significant cytotoxicity against P-388 and A-549 in vitro than VP-16. Among them, 9d exhibited most potent cytotoxicity against P-388 and A-549 cells (IC50 is <0.01 and 0.13 μM, respectively). Also, the antioxidative activities showed that the modified compounds of 4′-demethylepipodophyllotoxin (9a–d and 10a–c) are higher than those of podophyllotoxin series (8a–d). The relationship between the cytotoxity and antioxidative activity discussed.Target compounds with 4β-stable nitroxides and (or) 4′-hydroxyl ester showed generally superior cytotoxicities than VP-16, and their antioxidative activities were in accord with antitumor activities.
Co-reporter:Ying-Qian Liu;Hua Yang
Chinese Journal of Chemistry 2006 Volume 24(Issue 6) pp:785-790
Publication Date(Web):7 JUN 2006
DOI:10.1002/cjoc.200690149
Five novel compounds composed of etoposide and 5-fluorouracil derivatives joined by an ester linkage were prepared and evaluated for their antitumor potential. Most of these analogues have exhibited promising in vitro cytotoxic activity against cell cultures of murine leukaemia P-388 and human lung carcinoma A-549. The results presented herein challenged the long-standing structure-activity relationships, which proposed that a free 4′-hydroxyl group is essential structural requirement for etoposide-like activity. And in addition, the 4′-position was suggested to tolerate chemical modifications such as esterification. The preliminary testing results also indicated that the design and synthesis of these compounds were beneficial for therapeutic values of etoposide.
Co-reporter:Xuan Tian;Yuanjiang Pan;Hong Wang
Helvetica Chimica Acta 2003 Volume 86(Issue 10) pp:3320-3325
Publication Date(Web):10 NOV 2003
DOI:10.1002/hlca.200390274
The isolation, structure elucidation, and antitumor activity of four new sesquiterpene polyol esters, i.e., of 6α,13-bis(acetyloxy)-9β-(cinnamoyloxy)-1β-(furan-3-ylcarbonyl)oxy]-4α-hydroxy-β-dihydroagarofuran (1), 13-(acetyloxy)-9β-(benzoyloxy)-4α-hydroxy-1β,6α-bis[(2-methylbutanoyl)oxy]-β-dihydroagarofuran (2), 1β,6α,13- tri(acetyloxy)-9β-(cinnamoyloxy)-4α-hydroxy-β-dihydroagarofuran (3), and 6α,13-bis(acetyloxy)-9β-(benzoyloxy)-4α-hydroxy-1β-[(2-methylbutanoyl)oxy]-β-dihydroagarofuran (4), and of five known sesquiterpene polyol esters 5–9 from the seed oil of Euonymus nanoidesLoes. are reported (β-dihydroagarofuran=octahydro-2,2,5a,9-tetramethyl-2H-3,9a-methano-1-benzoxepin).
