Synthesis of Novel 1,3,5-Triazine Analogues With Selective Activity Against Pancreatic (Capan-1) and Colorectal...

A series of 2-(2-arylidenehydrazinyl)-4,6-bis(substituted-phenoxy)-1,3,5-triazines (compounds 3a-o to 7a-o) was synthesized and evaluated for DNA-binding affinity using calf thymus DNA. Based on their DNA interaction profiles, the top three compounds from each series were selected for in vitro anticancer screening against eight human cancer cell lines, encompassing both solid tumors (glioblastoma, pancreatic adenocarcinoma, colorectal carcinoma, and lung carcinoma) and hematological malignancies (acute lymphoblastic leukemia, acute myeloid leukemia, chronic myeloid leukemia, and non-Hodgkin lymphoma). Among the tested compounds, 5i and 7b demonstrated the highest anticancer potency against pancreatic adenocarcinoma (Capan-1), with IC₅₀ values of 2.4 and 1.9 µM, respectively. Notably, compound 5i also exhibited strong cytotoxicity against colorectal carcinoma (HCT-116), with an IC₅₀ of 2.2 µM. Additional analogues namely 3i, 3l, 6g, 6l, and 7m displayed IC₅₀ values ranging from 7.4 to 42.2 µM across the panel of cancer cell lines, highlighting the superior activity of 5i and 7b as promising antiproliferative agents. Molecular docking studies revealed that compound 7b formed strong interactions with the prenyl-binding protein PDEδ, and subsequent molecular dynamics simulations confirmed the stability of the 7b-PDEδ complex, supporting its potential as a targeted anticancer agent.