Premium
Design and Synthesis of Novel Cytotoxic Indole‐Thiosemicarbazone Derivatives: Biological Evaluation and Docking Study
Author(s) -
Bakherad Zohreh,
Safavi Maliheh,
Fassihi Afshin,
SadeghiAliabadi Hojjat,
Bakherad Mohammad,
Rastegar Hossein,
Saeedi Mina,
Ghasemi Jahan B,
Saghaie Lotfollah,
Mahdavi Mohammad
Publication year - 2019
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.201800470
Subject(s) - chemistry , ethidium bromide , acridine orange , semicarbazone , cytotoxicity , etoposide , indole test , stereochemistry , hep g2 , docking (animal) , cytotoxic t cell , combinatorial chemistry , bromide , apoptosis , quinazolinone , colchicine , chalcone , biochemistry , in vitro , organic chemistry , biology , medicine , dna , nursing , chemotherapy , genetics
In this work, two novel series of indole‐thiosemicarbazone derivatives were designed, synthesized, and evaluated for their cytotoxic activity against MCF‐7, A‐549, and Hep‐G2 cell lines in comparison to etoposide and colchicine as the reference drugs. Generally, the synthesized compounds showed better cytotoxicity towards A‐549 and Hep‐G2 than MCF‐7. Among them, (2 E )‐2‐{[2‐(4‐chlorophenyl)‐1 H ‐indol‐3‐yl]methylidene}‐ N ‐(4‐methoxyphenyl)hydrazinecarbothioamide ( 8l ) was found to be the most potent compound against A‐549 and Hep‐G2, at least three times more potent than etoposide. The morphological analysis by the acridine orange/ethidium bromide double staining test and flow cytometry analysis indicated that compound 8l induced apoptosis in A‐549 cells. Moreover, molecular docking methodology was exploited to elucidate the details of molecular interactions of the studied compounds with putative targets.