Quantum chemical calculations and molecular docking studies of 5-(4-chlorobenzylidene)thiazolidine-2,4-dione(CTD) and its mannich product 5-(4-chlorobenzylidene)-3-(morpholinomethyl)thiazolidine-2,4-dione (CMTD)

• Published in: Journal of molecular structure 2018-04, Vol.1157, p.177-190
• Main Authors: Fatma, Shaheen, Bishnoi, Abha, Verma, Anil Kumar, Singh, Vineeta, Srivastava, Krishna
• Format: Article
• Language: English
• Subjects: 3-Dehydroquinase; DFT studies; Molecular docking; NLO
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2017.12.051

This work presents the synthesis of 5-(4-chlorobenzylidene)thiazolidine-2,4-dione (CTD) by Claisen condensation of thiazolidine-2,4-dione and mannich product of CTD, 5-(4-chlorobenzylidene)-3-(morpholinomethyl)thiazolidine-2,4-dione (CMTD). The static first hyperpolarizability values for thiazolidine-2,4-dione derivatives have been calculated as 10.28 × 10−30 esu for CTD and 19.42 × 10−30 esu for CMTD. The gradual increase in hyperpolarizability values of synthesized thiazolidine-2,4-dione derivatives from CTD to CMTD is due to the blockage of NH group on CTD by mannich reaction. The structures of these compounds have been derived by spectroscopic(IR, UV, Mass, 1H and 13C NMR) analysis as well as with the help of theoretical studies. The high values of first static hyperpolarizability indicate that the synthesized derivatives are suitable as non–linear optical (NLO) material. CTD with MIC value of 12.5 μg/mL can be developed as an alternative drug for the treatment of enteric fever. Calculated frontier orbital gap values suggest that the CMTD is a soft molecule with high chemical reactivity and is more polarizable as compared to the CTD. Molecular electrostatic potential is calculated for the optimized geometry of the molecules to estimate their chemical reactivity. The inhibitor CTD forms a stable complex with 3-dehydroquinase enzyme of Salmonella typhi. It is evident from the ligand receptor interactions and a binding affinity value of −5.88 kcal/mol and an inhibition constant of 49.22 μM. This is further confirmed by the experimental biological data. The molecular docking studies are supportive of the antibacterial activity of CTD exhibiting high inhibition constant and binding energy. [Display omitted] •CMTD is better to be used as nlo material as compared to the CTD on the basis of calculated hyperpolarizability value.•CMTD is more polarizable and has high chemical reactivity as compared to CTD.•CTD is found to be more active against Salmonella typhi as compared to the CMTD.•Molecular docking results suggest that CTD might exhibit inhibitory activity against Salmonella Typhi.