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Synthesis and Anticancer Evaluation of 1,4‐Naphthoquinone Derivatives Containing a Phenylaminosulfanyl Moiety
Author(s) -
Ravichandiran Palanisamy,
Subramaniyan Sivakumar Allur,
Kim SeonYoung,
Kim JongSoo,
Park ByungHyun,
Shim Kwan Seob,
Yoo Dong Jin
Publication year - 2019
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201800749
Subject(s) - sulfonyl , hela , chemistry , apoptosis , cytotoxic t cell , stereochemistry , cytotoxicity , moiety , carboxamide , downregulation and upregulation , biochemistry , cell , gene , in vitro , organic chemistry , alkyl
1,4‐Naphthoquinones are exceptional building blocks in organic synthesis and have been used to synthesize several well‐known pharmaceutically active agents. Herein we report the synthesis, structural characterization, and biological evaluation of new phenylaminosulfanyl‐1,4‐naphthoquinone derivatives. We evaluated the cytotoxic activity of the synthesized compounds against three human cancer cell lines: A549, HeLa, and MCF‐7. Most of the synthesized compounds displayed potent cytotoxic activity. Specifically, compounds 5 e [3,5‐dichloro‐ N ‐(4‐((4‐((1,4‐dioxo‐3‐(phenylthio)‐1,4‐dihydronaphthalen‐2‐yl)amino)phenyl)sulfonyl)phenyl)benzamide], 5 f [ N ‐(4‐((4‐((1,4‐dioxo‐3‐(phenylthio)‐1,4‐dihydronaphthalen‐2‐yl)amino)phenyl)sulfonyl)phenyl)‐3,5‐dinitrobenzamide], and 5 p [ N ‐(4‐((4‐((1,4‐dioxo‐3‐(phenylthio)‐1,4‐dihydronaphthalen‐2‐yl)amino)phenyl)sulfonyl)phenyl)thiophene‐2‐carboxamide] showed remarkable cytotoxic activity. The synthesized compounds showed low toxicity in normal human kidney HEK293 cells. The cytotoxic mechanism of compounds 5 e , 5 f , and 5 p was explored in MCF‐7 cells. The results confirmed that these three compounds induce apoptosis and arrest the cell cycle at the G 1 phase. In addition, compounds 5 e , 5 f , and 5 p were found to induce apoptosis via upregulation of caspase‐3 and caspase‐7 proteins as well as by upregulation of the gene expression levels of caspases‐3 and ‐7. Our findings demonstrate that compounds 5 e , 5 f , and 5 p could be potent agents against a number of cancer types.