Design, synthesis of novel pyrazolopyridine derivatives and CREBBP bromodomain inhibitors docking and molecular dynamics

Abstract

A sequence of novel compounds pyrazolopyridine have been prepared by a general synthetic method. Due to high efficiency and selectivity, anticancer agents consisting of combined molecules have gained great interests. The IC50 values have been determined against cell line U937, the results obtained indicate the potential effects against cancer cell line. The cell potency of cell line is best for compounds <strong>4a</strong> IC50 = 62.5 μM, <strong>5b</strong> IC50 = 62.5 μM,<strong>4b</strong> IC50 = 31.2 μM, <strong>4e</strong> IC50 = 31.2 μM), selectivity and <em>in vivo</em>. Further, the molecular docking studies indicate that substituted pyrazolo[4,3-c]pyridine derivatives show good anticancer activity in the medicinal field. The ease of synthesis and the significant biological activities make these compounds potential new frameworks for progress of cancer therapeutics. Compound <strong>4f</strong> shows anticancer effect in cancer cell lines and <em>in vivo</em> that corresponds with antitumor activity in an AML cancer type. For the molecular docking with the ligands, the RMSD value has been calculated, the protein with the least RMSD is found to be 5KTU screening with 20 small molecules.