H2O2:HCl Catalyzed Synthesis of 5-(3-Substituted-Thiophene) Pyrimidine Derivatives and Evaluation for Their Pharmacological Effects

Abstract

A series of 5-(3-substituted-thiophene) pyrimidine derivatives (3a-d) were synthesized via Knoevenagel condensation reaction in aqueous ethanol using H2O2:HCl as a green halogenating catalyst and evaluated for their pharmacological effects. The structures of the targets were confirmed by analytical and spectroscopic methods. From antibacterial activity result reveals that, all the four compounds showed appreciable activity with varied zone of inhibition, in that the compounds 3b & 3d exhibited most effective zone of inhibition against bacterial strains E. coli & S. aureus respectively. In-vitro cytotoxicity was carried by MTT assay method against MCF-7 (Breast cancer) cell line and results of all the four compounds showed excellent selectivity, in that compound 3a exhibited excellent cytotoxicity with minimum cell viability range of 23.68 to 44.16 %. The interaction of compounds with CT-DNA was determined by using UV-absorption spectroscopy and results were confirmed that, all the synthesized compounds interacted strongly with CT-DNA through electrostatic or groove binding. In-silico ADME-toxicology results indicated that, all the targets are non-toxic, good oral bioavailability and druglikeness score indicated that they are suitable as drug-leads. From In-silico molecular docking results showed compound 3b was bound with GlcN-6-P and P38 MAPk with least binding energy of -7.9 and -6.4 kcal/mol respectively.