TARGET-BASED APPROACH FOR IN SILICO STUDIES, DESIGN, SYNTHESIS, AND ANTIULCEROGENIC POTENTIAL OF NOVEL 1,4 DIHYDROPYRIDINE DERIVATIVES

In-silico studies play a very crucial role in medicinal chemistry and synthesis of the lead compound. As we know that 1,4-Dihydropyridine is a versatile molecule, and previous studies have shown that it possesses therapeutic activity in different diseases, such as anticancer, anticonvulsant, anticoagulant, anti-Alzheimer, antitubercular antiulcer. As described by the researchers, 1,4 Dihydropyridine with sulphanilamide substitution possess good antiulcer activity so, here, in our research work, we decided to synthesized 1,4 dihydropyridine derivative by replacement with some other free amine group-containing compound to determine the antiulcer property of 1,4 Dihydropyridine. To keep this in mind, we studied its interaction with receptor site (H⁺/K⁺ ATPase pump), which was obtained from protein data bank (PDB) and a series of 1,4-Dihydropyridine hybrid molecule synthesized. The binding of the molecule with receptor site investigated by molecular docking studies and drug-like illness of these compound predicted by using Schrodinger maestro suite 2018-4. Omeprazole and Lansoprazole were used as a standard to validate the docking results. Synthesized molecule characterized by spectroscopic methods and evaluated for their in-vivo antiulcerogenic activity using Albino rats (Weight 125g to 200g). Among all the Synthesized compounds, A5, A6, B5, and B6 show significant activity in comparison to omeprazole and, among all four compounds, A5 and B6 (30mg/kg) possess the most potent antiulcer activity. These results indicate that 1,4-Dihydropyridine, is a successful calcium channel blocker, also shows the antiulcer potential, and all synthesized compound can serve as antiulcer drug after further investigation.