Department Of Pharmaceutical Sciences and Natural Products
Permanent URI for this communityhttps://kr.cup.edu.in/handle/32116/52
Browse
2 results
Search Results
Item Pyrimidine containing epidermal growth factor receptor kinase inhibitors: Synthesis and biological evaluation(Blackwell Publishing Ltd, 2017) Joshi, Gaurav; Nayyar, Himanshu; Kalra, Sourav; Sharma, Praveen; Munshi, Anjana; Singh, Sandeep; Kumar, RajStructure-based design and synthesis of pyrimidine containing reversible epidermal growth factor receptor (EGFR) inhibitors 1a?d are reported. The compounds (1a?d) inhibited the EGFR kinase activity in vitro with IC50 range 740?nm to 3??m. mRNA expression of EGFR downstream target genes, that is twist, c-fos and aurora were found to be altered upon treatment with compounds 1a?d. The compounds 1a?d exhibited excellent anticancer activity at low micromolar level (3.2?9??m) in lung, colon and breast cancer cell lines. Furthermore, compounds induced the alteration in mitochondrial membrane potential and reactive oxygen species level and. Selected compound 1b was found to increase sub-G1 population indicative of cell death, the mode of cell death was apoptotic as evident from Annexin V verses propidium iodide assay. Molecular modelling further helped to investigate the binding recognition pattern of the compounds in ATP binding EGFR domain similar to erlotinib and dissimilar to WZ4002. ? 2017 John Wiley & Sons A/S.Item Pyrimidine-fused derivatives: Synthetic strategies and medicinal attributes(Bentham Science Publishers B.V., 2016) Joshi, Gaurav; Nayyar, Himanshu; Alex, Jimi Marin; Vishwakarma, Gajendra S.; Mittal, Sunil; Kumar, RajPyrimidine-fused derivatives traits the inextricable part of DNA and RNA, exhibit indispensable role in numerous biological processes, possessing momentous chemical and biological importance. Pyrimidine-condensed derivatives as the pharmacophore exhibit broad spectrum of biological activities encompassing antitubercular, antibacterial, antifungal, antiviral, anti-inflammatory, antimalarial, anticancer and anti-HIV. Several retrosynthetic approaches, are available for the synthesis of pyrimidine-fused analogues which offers enormous scope in the field of medicinal chemistry. Ring fused pyrimidine and their innumerable derivatives continue to hold the attention of chemists since their presence in the biologically active resources have been known to elicit additive effects on the bio-efficacy of the molecules. The present review is a concerted effort to congregate information mainly focusing on the comprehensive categorization of pyrimidine ring based on their fusion with five, six, seven and eight-membered ring(s). Moreover, it also puts forward their systematic nomenclature, synthetic strategies, and bioactivities including SAR studies. This review is being put forwarded with an incentive to provide researchers with a comprehensive and updated literature. In addition, the manuscript also brings to light the various pharmacophore designs based on fusedpyrimidine ring system, delving deeper into synthesis and the subsequent generation of new libraries of pyrimidine-fused derivatives including their biological assessments. ? 2016 Bentham Science Publishers.