Abstract

DESIGN OF NOVEL 1, 3, 5 TRIAZINES AS ANTI CANCER AGENTS TARGETING AS DIHYDROFOLATE REDUCTASE ENZYMES (HUMAN DHFR): IN SILICO STUDIES

Srinija Sakala* and R. Govindarajan

Abstract

Docking is routinely used for understanding drug‐receptor interaction in modern drug design. We focused on the docking of 1, 3, 5 Triazines derivatives as inhibitors to human dihydrofolate reductase (DHFR). We docked 15 derivatives collected from literature to DHFR and studied their specific interactions with DHFR. A new shape-based method, Ligand Fit, was used for docking 1, 3, 5 triazines derivatives into DHFR active sites. The result indicates that the docking approach is reliable and produces a good correlation coefficient (r= 0.156) for the 15 compounds between docking score and IC50 values (Inhibitory Activity). The nitrogen substituted triazine ring of compound 1 makes significant hydrophobic contact with Glu 30, Phe 31 and Phe 34 of the DHFR active site leading to enhanced inhibition of the enzyme. The docked complexes provide better insights to design more potent DHFR inhibitors prior to their synthesis.

Keywords: DHFR inhibitors, IC50, docking, drug, receptor.