127882-75-1Relevant academic research and scientific papers
SAR analysis and biological studies of synthesized podophyllum derivates obtained by N linkage modification at C-4 position
Wang, Huai,Tang, Lijun,Tang, Yajie,Yuan, Zhanpeng
, p. 6183 - 6192 (2014)
A series of C4-N-substituted podophyllum derivatives were synthesized and tested for cytotoxicity in HeLa, BGC-823, A549, Huh7 and MCF-7 cells by MTT assay. Pharmacologically, most derivatives displayed potent cytotoxicity against at least one of the tested tumor cell lines. Structure activity relationship (SAR) analysis suggests that compounds with imidogen exposed on the pyridine, rather than pyrimidine, exhibited significantly elevated potency. Moreover, the presence of a chlorine atom in the heterocyclic ring enhanced cytotoxicity, with the order 3-position > 4-position > 5-position > 6-position. Specifically, two compounds, 3g and 3h, with 2-amino-3-chloropyridine substituted into the podophyllotoxin (PPT) and 4′-O-demethylepipodophyllotoxin (DMEP) scaffolds were shown to have the most potent HeLa cells cytotoxicity compared to other synthesized derivatives or reference compounds PPT, DMEP and etoposide (VP-16). The compound 3g was shown to inhibit microtubule polymerization and compound 3h affected topoisomerase II catalytic activity. Both compounds resulted in G2/M phase arrest and apoptosis, purportedly by increasing the expression of P53, followed by Bax up-regulation, Bcl-2 down-regulation, and caspase-3 activation. As a result of this work, we conclude that compounds 3g and 3h are more potent anticancer agents than VP-16, and that they work by different antitumor mechanisms.
Antitumor agents. 113. New 4β-arylamino derivatives of 4'-O-demethylepipodophyllotoxin and related compounds as potent inhibitors of human DNA topoisomerase II
Wang,Kuo,Schnur,Bowen,Liu,Han,Chang,Cheng,Lee
, p. 2660 - 2666 (2007/10/02)
A number of 4'-O-demethylepipodophyllotoxin derivatives possessing various 4β-N-, 4β-O- or 4β-S-aromatic rings have been synthesized and evaluated for their inhibitory activity against the human DNA topoisomerase II as well as for their activity in causin
