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Synthesis and biological evaluation of morpholines linked coumarin–triazole hybrids as anticancer agents
Author(s) -
Goud Nerella Sridhar,
Pooladanda Venkatesh,
Mahammad Ghouse S.,
Jakkula Pranay,
Gatreddi Santhosh,
Qureshi Insaf A.,
Alvala Ravi,
Godugu Chandraiah,
Alvala Mallika
Publication year - 2019
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.13578
Subject(s) - coumarin , chemistry , in vitro , apoptosis , binding constant , a549 cell , mtt assay , cytotoxicity , stereochemistry , cell culture , docking (animal) , triazole , microbiology and biotechnology , biochemistry , binding site , biology , medicine , nursing , organic chemistry , genetics
A series of novel morpholines linked coumarin–triazole hybrids ( 6a–6v ) has been synthesized and evaluated for their anti‐proliferative potential on a panel of five human cancer cell lines, namely bone ( MG ‐63), lung (A549), breast ( MDA ‐ MB ‐231), colon ( HCT ‐15) and liver (HepG2), using MTT assay. Among all, the compound 6n {7‐((1‐(2,4‐dichlorobenzyl)‐1H‐1,2,3‐triazol‐4‐yl) methoxy)‐4‐((2,6‐dimethylmorpholino) methyl)‐2H‐chromen‐2‐one} showed significant growth inhibition against MG ‐63 cells with an IC 50 value of 0.80 ± 0.22 μM. Further, induction of apoptosis by 6n of MG ‐63 cells confirmed as a result of morphological changes, the sub‐G1 phase arrest, increased percentage of apoptotic cells, and decrease in mitochondrial membrane potential and increase in reactive oxygen species levels. The in vitro Gal‐1 expression in cell culture supernatant of MG ‐63 cells treated with compound 6n showed dose‐dependent reduction. The binding constant ( K a ) of 6n with Gal‐1 was calculated from the intercept value which was observed as 3.0 × 10 5 M −1 by fluorescence spectroscopy. Surface plasmon resonance showed that 6n binds to Gal‐1 with binding constant ( K a ) of 1.29E+04 1/Ms and equilibrium constant KD value of 7.54E−07 M, respectively. Molecular docking studies revealed the binding interactions of 6n with Gal‐1.