IN-SILICO DRUG DESIGN AND SYNTHESIS OF NOVEL 2- AMINOTHIOPHENE AS ANTI-CANCER AGENTS

Cancer is the major worldwide problem. It arises due to uncontrolled growth of cells. While there have been many remarkable breakthroughs in cancer research, there is still a need for the development of new therapies that target the different mechanisms of cancer cells. Therefore, the focus of our research is identifying novel hit molecules targeting Poly (ADP-ribose) polymerase 1(PARP-1). PARP-1 is a critical enzyme involved in DNA damage repair and recombination, and shows great potential for drug development in the treatment of cancers with defective DNA repair. Thiophene and its derivative can lead in the future to synthesize varieties of chemotherapeutic entities in the field of cancer treatment. Chemistry of 2-aminothiophenes is arguably one of the most extensive and dynamic field of present-day thiophene research. A series of novel PARP-1 inhibitor derivatives were designed and computationally optimized to investigate the maximum interaction between designed ligands and proteins from protein data bank (PDB) with an advantage of reduced cost and time. Docking studies were performed using PyRx software. All the designed ligands showed mild to excellent binding with protein(4RV6) and it was found that out of 4 designed ligand, PR2 ligand showed the best binding with 4RV6. Gewald reaction is the universal method for synthesis of substituted 2 aminothiophenes. Consequently, details about the proposed mechanism of Gewald-like reactions and the wide scope of substituted 2-aminothiophenes for real life applications. The substituted 2-aminothiophene-3-carboxamide was synthesized in our laboratory.