6P - Quinazoline clubbed s-triazine derivatives as VEGFR2 kinase inhibitor: Design, synthesis, docking, antiproliferative and antiangiogenic activity on...
|Date||17 December 2016|
|Event||ESMO Asia 2016 Congress|
|Topics|| Basic Science
|Citation||Annals of Oncology (2016) 27 (suppl_9): ix1-ix8. 10.1093/annonc/mdw573|
A. Verma1, P. Pathak1, P.K. Shukla1, V. Kumar1, A. Kumar2, A.K. Singh3
Angiogenesis is a fundamental and complex process of endothelial cells, pericytes and responsible for executing normal physiological responses like wound healing, embryonic development and bone remodelling etc. Judah Folkman and colleagues established the concept of angiogenic inhibition in tumour growth. The epidermal growth factor (EGF) receptor (EGFR) and vascular endothelial growth factor (VEGF) pathways play an important role in the growth, metastatic potential of tumours and their inhibition is a prime target for various therapeutic agents including quinazoline based compounds because it represents the most validated signalling pathway. Considering that we have developed quinazoline clubbed 1,3,5-s-triazine derivatives (QCTD) as a potential inhibitor of VEGFR2 kinase for anti-cancer activity.
Designing of (QCTD) was done on the basis of molecular field mapping and alignment studies with standard angiogenic inhibitor vandetanib. Further docking studies were performed by Autodock 4.2 for most promising similar designed derivatives and all screened (QCTD) were developed via cost-effective synthetic route. The synthesized derivatives were evaluated for their in-vitro anti-cancer activity on four different cell line HeLa (Human Cervical Carcinoma), MCF-7 (Breast Carcinoma), HL-60 (Human promyelocytic leukemia) and HepG2 (Human Hepatocellular carcinoma) and and also in-ovo angiogenic inhibition was performed on chick embryo.
All the designed derivatives explored more than 50% similar pattern of field and atomic arrangement. Thiourea (8b), chloranilino(8d), hrdrazicarboxamide(8j) and methylamino(8m) substituted derivatives selected for docking calculations due to higher similarity value. Docking studies revealed significant result like standard drug vandetanib on protein VEGFR2 kinase (PDB ID: 3EWH). IC50 report clearly marked that derivatives have significant antiproliferative action against wide verity of cancer cell line and in-ovo result explored that derivatives are non-toxic to the normal cells.
We have developed a novel class of anticancer agents.
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All authors have declared no conflicts of interest.