Design, synthesis and biological evaluation of lapachol derivatives possessing indole scaffolds as topoisomerase I inhibitors.
A series of novel lapachol derivatives possessing indole scaffolds was designed and synthesized. The in vitro anti-proliferative activity of these novel compounds was evaluated in Eca109 and Hela cell lines. Almost all the tested compounds showed manifested potent inhibitory activity against the two tested cancer cell lines. Topo I-mediated DNA relaxation activity indicated that these novel compounds have potent Topoisomerase I inhibition activity. The most potent compounds 4n and 4k demonstrated more cytotoxicity than camptothecin and was comparable to camptothecin in inhibitory activities on Topoisomerase I in our biological assay. In addition, the Hoechst 33342 staining method also showed that the complex can induce Hela cell apoptosis.
School of Pharmacy, Xinxiang Medical University, Xinxiang 453003, China. Electronic address: zhangchong2006@163.com.
Chong
C
Zhang
Basic Medicine College, Xinxiang Medical University, Xinxiang 453003, China.
Yan
Y
Qu
School of Pharmacy, Xinxiang Medical University, Xinxiang 453003, China.
Bingxuan
B
Niu
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004264:DNA Topoisomerases, Type I / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006801:Humans; D015394:Molecular Structure; D009285:Naphthoquinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D059004:Topoisomerase I Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
D000970:Antineoplastic Agents; D009285:Naphthoquinones; D059004:Topoisomerase I Inhibitors; C008252:lapachol; D004264:DNA Topoisomerases, Type I
Anti-proliferative; Indole; Lapachol; Molecular hybridization; Topoisomerase I