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Synthesis and Biological Assays of 9‐(Acylamino)homocamptothecins as DNA Topoisomerase I Inhibitors
Author(s) -
Guo Wei,
Dong Guoqiang,
Zhu Lingjian,
Liu Wenfeng,
Zhuang Chunlin,
Guo Zizhao,
Yao Jianzhong,
Sheng Chunquan,
Zhang Huojun,
Miao Zhenyuan,
Zhang Wannian
Publication year - 2013
Publication title -
chemistry and biodiversity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.427
H-Index - 70
eISSN - 1612-1880
pISSN - 1612-1872
DOI - 10.1002/cbdv.201200311
Subject(s) - chemistry , topoisomerase , dna , topoisomerase inhibitor , biochemistry , biological activity , computational biology , in vitro , biology
In an effort to improve the stability of homocamptothecin and reduce the toxicity, novel homocamptothecin analogs with acylamino groups at C(9) were designed and synthesized. The cytotoxic activities of all the synthetic compounds against three cancer cell lines were evaluated by the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl‐2 H ‐tetrazolium bromide (MTT) assay, and irinotecan was used as reference compound. Compound 7c with a piperidinylacetamido group and 10a with phenylacetamido group at C(9) showed potent activities both in vitro and in vivo. In addition, they also revealed remarkable topoisomerase I inhibitions which were exhibited with well‐established bonds with amino acid residues Arg364 and Asp533 in the active pocket. On the basis of the biological activities, 7c and 10a would be potential candidates for further studies.