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Synthesis and biological evaluation of novel 7-acyl homocamptothecins as Topoisomerase I inhibitors.
Eur J Med Chem. 2011 Jun; 46(6):2408-14.EJ

Abstract

A series of novel 7-acyl derivatives of homocamptothecin (hCPT) were designed and synthesized with the purpose to improve antitumor activity of hCPT, via Minisci free-radical reaction from 10-methoxyhomocamptothecin. All the compounds were evaluated for in vitro cytotoxicity against three cancer cell lines (A549, MDA-MB-435 and HCT116). For MDA-MB-435 cell line, compounds, 6a, 6b, 6k and all of 7-alkylcabonyl homocamptothecin derivatives showed higher in vitro inhibitory activities than topotecan (TPT). Furthermore, compounds 6d, 6e, and 6k showed highly potent inhibitory activities with the IC50 values from less than 1 nM to 2.2 nM. In Topoisomerase I (Topo I)-induced DNA cleavage assay, compounds 6a, 6d, and 6k, as compared to CPT, revealed higher Topo I inhibitory activity.

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Authors+Show Affiliations

Liu W
School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, People's Republic of China.
Zhu L
No affiliation info available
Guo W
No affiliation info available
Zhuang C
No affiliation info available
Zhang Y
No affiliation info available
Sheng C
No affiliation info available
Cheng P
No affiliation info available
Yao J
No affiliation info available
Wang W
No affiliation info available
Dong G
No affiliation info available
Wang S
No affiliation info available
Miao Z
No affiliation info available
Zhang W
No affiliation info available

MeSH

Antineoplastic AgentsCamptothecinCell ProliferationCrystallography, X-RayDNA Topoisomerases, Type IDose-Response Relationship, DrugDrug DesignDrug Screening Assays, AntitumorHumansModels, MolecularMolecular StructureStereoisomerismStructure-Activity RelationshipTopoisomerase I InhibitorsTumor Cells, Cultured

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21463912

Citation

Liu, Wenfeng, et al. "Synthesis and Biological Evaluation of Novel 7-acyl Homocamptothecins as Topoisomerase I Inhibitors." European Journal of Medicinal Chemistry, vol. 46, no. 6, 2011, pp. 2408-14.
Liu W, Zhu L, Guo W, et al. Synthesis and biological evaluation of novel 7-acyl homocamptothecins as Topoisomerase I inhibitors. Eur J Med Chem. 2011;46(6):2408-14.
Liu, W., Zhu, L., Guo, W., Zhuang, C., Zhang, Y., Sheng, C., Cheng, P., Yao, J., Wang, W., Dong, G., Wang, S., Miao, Z., & Zhang, W. (2011). Synthesis and biological evaluation of novel 7-acyl homocamptothecins as Topoisomerase I inhibitors. European Journal of Medicinal Chemistry, 46(6), 2408-14. https://doi.org/10.1016/j.ejmech.2011.03.024
Liu W, et al. Synthesis and Biological Evaluation of Novel 7-acyl Homocamptothecins as Topoisomerase I Inhibitors. Eur J Med Chem. 2011;46(6):2408-14. PubMed PMID: 21463912.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Synthesis and biological evaluation of novel 7-acyl homocamptothecins as Topoisomerase I inhibitors. AU - Liu,Wenfeng, AU - Zhu,Lingjian, AU - Guo,Wei, AU - Zhuang,Chunlin, AU - Zhang,Yongqiang, AU - Sheng,Chunquan, AU - Cheng,Pengfei, AU - Yao,Jianzhong, AU - Wang,Wenya, AU - Dong,Guoqiang, AU - Wang,Shengzheng, AU - Miao,Zhenyuan, AU - Zhang,Wannian, Y1 - 2011/03/23/ PY - 2011/01/11/received PY - 2011/03/07/revised PY - 2011/03/13/accepted PY - 2011/4/6/entrez PY - 2011/4/6/pubmed PY - 2011/9/13/medline SP - 2408 EP - 14 JF - European journal of medicinal chemistry JO - Eur J Med Chem VL - 46 IS - 6 N2 - A series of novel 7-acyl derivatives of homocamptothecin (hCPT) were designed and synthesized with the purpose to improve antitumor activity of hCPT, via Minisci free-radical reaction from 10-methoxyhomocamptothecin. All the compounds were evaluated for in vitro cytotoxicity against three cancer cell lines (A549, MDA-MB-435 and HCT116). For MDA-MB-435 cell line, compounds, 6a, 6b, 6k and all of 7-alkylcabonyl homocamptothecin derivatives showed higher in vitro inhibitory activities than topotecan (TPT). Furthermore, compounds 6d, 6e, and 6k showed highly potent inhibitory activities with the IC50 values from less than 1 nM to 2.2 nM. In Topoisomerase I (Topo I)-induced DNA cleavage assay, compounds 6a, 6d, and 6k, as compared to CPT, revealed higher Topo I inhibitory activity. SN - 1768-3254 UR - https://www.unboundmedicine.com/medline/citation/21463912/Synthesis_and_biological_evaluation_of_novel_7_acyl_homocamptothecins_as_Topoisomerase_I_inhibitors_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0223-5234(11)00238-8 DB - PRIME DP - Unbound Medicine ER -