EVALUATION OF NOVEL PYRIDO[4,3-D]PYRIMIDINES ATTACHED WITH PIPERAZINE DERIVATIVES AT 2,5-POSITIONS AS CDK-1 INHIBITORS (PANCREATIC CANCER) THROUGH IN SILICO STUDIES

Rajendra Swami Mareedu, Pandeeswaran M.*, Prashanth Nayak K., Selvakumar Balaranaman, Vaithiyanathan Mahendran, Satyapavan V., Aruna D., Varunkumar R., Panneer Selvam

A range of novel 2,5-piperazino substituted pyrido[4,3-d]pyrimidines aiming of enriching their biological activity have been designed and synthesized through multistep process. The structures were characterized using spectroscopic techniques such as 1H NMR, 13C NMR, LCMS and elemental analysis. The derivatives were evaluated in silico for their potential as Cyclin Dependent Kinase-1 (CDK-1) inhibitors in pancreatic cancer. In silico ADME predictions suggested favourable drug-likeness and pharmacokinetic properties. Molecular docking against CDK1 showed that compound 7e had the lowest binding energy, similar to Dinaciclib, which is an investigational drug for cancer. Compounds 7a, 7h, and 7i exhibited binding affinities close to the standard drug. These findings indicates that that 7e could be a promising therapeutic agent for CDK1 inhibition in cancer, particularly pancreatic cancer.