PMID: 11334569May 4, 2001Paper

Synthesis and biological evaluation of novel A-ring modified hexacyclic camptothecin analogues

Journal of Medicinal Chemistry
D K KimW S Choi

Abstract

Eleven A-ring modified hexacyclic analogues of camptothecin (CPT) containing a 1,4-oxazine ring were synthesized from 10-hydroxycamptothecin (11a) and 7-ethyl-10-hydroxycamptothecin (3) (SN-38) in four to five steps and were subjected to the biological tests such as cytotoxicity, topoisomerase I (Topo I) inhibitory activity, acetylcholinesterase (AChE) inhibition, and stability in human plasma. Four compounds 15a, 15b, 16a, and 16c were about 2-fold more potent than topotecan and as potent as CPT toward human cancer cell lines A549, H128, WiDr, MKN45, SK-OV-3, and SK-BR-3 in vitro, even though the most active compound 15b was slightly less potent than SN-38. The potency of Topo I inhibition of these compounds showed relatively good correlation with their cytotoxicity. Most of the compounds exhibited AChE inhibitory activity weaker (9 +/- 2 to 20 +/- 3%) than CPT (23 +/- 5%) or topotecan (20 +/- 4%) and similar to SN-38 (13 +/- 2%), indicating that they might have little effect on causing early diarrhea. The stability of lactone forms of these compounds in human plasma seemed to be much higher than that of CPT and similar to that of topotecan but lower than that of SN-38. Among the new hexacyclic CPT analogues, compound 15b show...Continue Reading

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Citations

May 26, 2005·Bioorganic & Medicinal Chemistry Letters·Heyong GaoWei Lu
Jan 29, 2013·European Journal of Medicinal Chemistry·Yikai ZhangKe Li
Jul 9, 2013·European Journal of Medicinal Chemistry·Lan-Xiang LiuXiao-Dong Yang
Aug 8, 2013·European Journal of Medicinal Chemistry·Zhiliang LvKe Li
May 7, 2005·International Journal of Pharmaceutics·Li DiHong Chen
Dec 17, 2002·Critical Reviews in Oncology/hematology·Christian Bailly
Jan 30, 2010·Molecular Pharmaceutics·Vincent J Venditto, Eric E Simanek
Jun 9, 2005·Natural Product Research·Dharmarajan SriramTanushree Ratan Bal
Jan 24, 2007·Acta Pharmacologica Sinica·Ai-jun LuHua-liang Jiang
Jul 2, 2014·European Journal of Medicinal Chemistry·Guillermo Rodríguez-BernaAvelino Corma
Dec 11, 2007·International Journal of Cancer. Journal International Du Cancer·Alessia GrozioPatrizia Russo
Jul 1, 2004·Bioorganic & Medicinal Chemistry Letters·Yuan-gang ZuWei Wang
Dec 6, 2008·Bioorganic & Medicinal Chemistry Letters·Qingyong LiLimin Wang
Dec 11, 2014·Organic & Biomolecular Chemistry·Xiao-Liang XuXiao-Dong Yang
Mar 10, 2017·Bioorganic & Medicinal Chemistry Letters·Chao-Bo ZhangXiao-Dong Yang
Jun 18, 2017·Organic & Biomolecular Chemistry·K Anil KumarParthasarathi Das
Feb 13, 2018·Chemical Biology & Drug Design·Yan-Hua LiLi-Juan Yang
Dec 21, 2018·Chemical Biology & Drug Design·Angel H RomeroAlvaro Morales
Dec 23, 2008·Chemical Reviews·Rajeshwar P Verma, Corwin Hansch
Jul 28, 2006·Bioorganic & Medicinal Chemistry·Qingyong LiLei Li
Jul 25, 2018·ACS Combinatorial Science·Petra KrálováMiroslav Soural
Jul 20, 2018·ACS Omega·Saikat MukherjeeRaja Shunmugam
Mar 10, 2009·Bioorganic & Medicinal Chemistry Letters·Xiao-Dong YangHong-Bin Zhang

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