Synthesis of novel bioactive pyrido[2,3- <i>d</i> ]pyrimidine derivatives with potent cytotoxicity through apoptosis as PIM-1 kinase inhibitors
Eman S. Tantawy, Mohamed S. Nafie, Hesham A. Morsy, Hassan A. El‐Sayed, Ahmed H. Moustafa, Samar M. Mohammed
Abstract
= 16.7 nM, with 95.6% inhibition). Moreover, compound 4 significantly activated apoptosis in MCF-7 cells, increasing the cell apoptosis by 58.29-fold by having 36.14% total apoptosis in treated cells compared to 0.62% for control. Moreover, it arrested the cell cycle at the G1 phase. PIM-1 kinase inhibition was virtually elucidated by the molecular docking study, highlighting binding interactions of the lead compound 4 towards the PIM-1 protein. Accordingly, compound 4 was validated as a promising PIM-1 targeted chemotherapeutic agent to treat breast cancer.
Topics & Concepts
PyrimidineCytotoxicityChemistryApoptosisKinaseCombinatorial chemistryStereochemistryPharmacologyBiochemistryIn vitroBiologyCancer Mechanisms and TherapySynthesis and biological activitySynthesis and bioactivity of alkaloids