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Synthesis, Biological Evaluation, and Autophagy Mechanism of 12N-Substituted Sophoridinamines as Novel Anticancer Agents.

ABSTRACT: A series of 12N-substituted sophoridinamine derivatives were synthesized and evaluated for their cytotoxic activities in human HepG2 hepatoma cells. Structure-activity relationship revealed that introduction of a suitable arylidene or arylethyl at the N'-end could greatly enhance antiproliferation potency. Among them, compound 6b possessing a N'-trimethoxyphenyl methylene exhibited potent antiproliferation effect against three human tumor cell lines including HepG2, leukemia (K562), and breast cancer (HMLE), with IC₅₀ between 0.55 and 1.7 ?M. The underlying mechanism of 6b against tumor cells is to block autophagic flux, mainly through neutralizing lysosomal acidity. Our results indicated that compound 6b is a potent lysosomal deacidification agent and is accordingly able to block autophagic flux and inhibit tumor cell growth.

SUBMITTER: Bi C

PROVIDER: S-EPMC5304307 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Synthesis, Biological Evaluation, and Autophagy Mechanism of 12N-Substituted Sophoridinamines as Novel Anticancer Agents.

Bi Chongwen C Zhang Na N Yang Peng P Ye Cheng C Wang Yanxiang Y Fan Tianyun T Shao Rongguang R Deng Hongbin H Song Danqing D

ACS medicinal chemistry letters 20170105 2

A series of 12N-substituted sophoridinamine derivatives were synthesized and evaluated for their cytotoxic activities in human HepG2 hepatoma cells. Structure-activity relationship revealed that introduction of a suitable arylidene or arylethyl at the N'-end could greatly enhance antiproliferation potency. Among them, compound 6b possessing a N'-trimethoxyphenyl methylene exhibited potent antiproliferation effect against three human tumor cell lines including HepG2, l ...[more]

PMID: 28197320

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