Design, Synthesis, Docking Studies and Molecular Dynamics Simulation of New 1,3,5‐Triazine Derivatives as Anticancer Agents Selectively Targeting Pancreatic Adenocarcinoma (Capan‐1)

Abstract

On the basis of remarkable anticancer profile of s‐triazine nucleus, a new series of 2‐methoxy‐4‐(3‐morpholino‐5‐(arylamino)phenoxy)benzaldehyde derivatives 11 a–u was prepared and evaluated for in vitro antiproliferative activity against eight diverse human cancer cell lines (Capan‐1, HCT‐116, LN229, NCI‐H460, DND‐41, HL‐60, K562 and Z138). Compounds 11 o, 11 r and 11 s were the most potent anticancer agents on pancreatic adenocarcinoma (Capan‐1) cell line with IC50 value of 1.4, 5.1 and 5.3 μM, respectively, while compounds 11 f, 11 g, 11 k, 11 l and 11 n displayed selective activity against the pancreatic adenocarcinoma (Capan‐1) cell line with IC50 values of 7.3–11.5 μM. These results indicate that derivative 11 o may serve as a promising lead compound for the ongoing development of novel antiproliferative agents. The docking studies were conducted to predict the interactions of derivative 11 o with putative protein targets in pancreatic adenocarcinoma (Capan‐1) cell line, specifically the prenyl‐binding protein PDEδ. Furthermore, the analysis of the molecular dynamics simulation results demonstrated that complex 11 o promoted a higher stability to the prenyl‐binding protein PDEδ.