Open AccessDesign and synthesis of substituted (1-(benzyl)-1H-1,2,3-triazol-4-yl)(piperazin-1-yl)methanone conjugates: study on their apoptosis inducing ability and tubulin polymerization inhibition
Author(s) -
Kesari Lakshmi Manasa,
Sowjanya Thatikonda,
Dilep Kumar Sigalapalli,
Sowmya Vuppaladadium,
Ganthala Parimala Devi,
Chandraiah Godugu,
Mallika Alvala,
Narayagesh,
Bathini Nagendra Babu
Publication year - 2020
Publication title -
rsc medicinal chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.754
H-Index - 55
ISSN - 2632-8682
DOI - 10.1039/d0md00162g
Subject(s) - apoptosis , conjugate , chemistry , polymerization , microtubule , tubulin , stereochemistry , biochemistry , biology , organic chemistry , microbiology and biotechnology , polymer , mathematics , mathematical analysis
A library of substituted (1-(benzyl)-1 H -1,2,3-triazol-4-yl)(piperazin-1-yl)methanone derivatives were designed, synthesized and screened for their in vitro cytotoxic activity against BT-474, HeLa, MCF-7, NCI-H460 and HaCaT cells by employing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Among all the synthesized analogues, compound 10ec displayed the highest cytotoxicity with the IC 50 value of 0.99 ± 0.01 μM towards BT-474 cancer cell line. The target compound ( 10ec ) was also evaluated for its tubulin polymerization inhibition study. Detailed biological studies such as acridine orange/ethidium bromide (AO/EB), DAPI and annexin V-FITC/propidium iodide staining assay suggested that compound 10ec induced the apoptosis of BT-474 cells. The clonogenic assay revealed that the inhibition of colony formation in BT-474 cells by 10ec in concentration-dependent manner. Moreover, the flow cytometric analysis revealed that 10ec induced apoptosis via cell cycle arrest at the sub-G1 and G2/M phase. In silico studies of sulfonyl piperazine-integrated triazole conjugates unveil that they possess drug-like properties. According to the molecular modelling studies, compound 10ec binds to the colchicine binding site of the tubulin.