Synthesis, stereochemistry determination, pharmacological studies and quantum chemical analyses of bisthiazolidinone derivative

A new compound (3) bisthaizolidinone derivative was synthesized by Knoevenagel condensation reaction. The structure of synthesized compound was elucidated by different spectral techniques and X-ray diffraction studies. The stereochemistry of the compound (3) was determined by H-1-H-1 NOESY, H-1-H-1 NMR COSY and single crystal X-ray diffraction studies as (Z, Z)-configuration. The computational quantum chemical studies of compound(3) like, IR, UV, NBO analysis were performed by DFT with Becke-3-Lee-Yang-Parr (B3LYP) exchange-correlation functional in combination with 6-311++G(d,p) basis sets. The DNA-binding of compound (3) exhibited a moderate binding constant (K-b = 1 x 10(5) Lmol(-1)) with hypochromic shift. The molecular docking displayed good binding affinity -7.18 kcal/mol. The MTT assay of compound (3) was screened against different cancerous cell lines, HepG2, Siha, Hela and MCF-7. Studies against these cell lines depicted that the screened compound (3) showed potent inhibitory activity against HepG2 cell (IC50 = 7.5 mu M) followed by MCF-7 (IC50 = 52.0 mu M), Siha (IC50 = 66.98 mu M), Hela (IC50 = 74.83 mu M) cell lines, and non-toxic effect against non-cancerous HEK-293 cells (IC50 = 287.89 mu M) at the concentration range (0-300) Furthermore, cell cycle perturbation was performed on HepG2 & Siha cell lines and observed that cells were arrested in G2/M in HepG2, and G0/G1 in Siha cell lines with respect to untreated control. Hence, compound (3) possesses potent anti cancerous activity against HepG2 cell line. (C) 2016 Elsevier B.V. All rights reserved.