Design, synthesis and anticancer studies of novel aminobenzazolyl pyrimidines as tyrosine kinase inhibitors

Chikhale, Rupesh ORCID: (2018) Design, synthesis and anticancer studies of novel aminobenzazolyl pyrimidines as tyrosine kinase inhibitors. Bioorganic Chemistry, 77. pp. 84-100. ISSN 0045-2068

Full text not available from this repository.


Abnormal signalling from the Protein tyrosine kinases (PTKs) like receptor tyrosine kinases and intracellular tyrosine kinases can lead to diseases such as cancer especially non-small cell lung cancer, chronic myeloid leukaemia and gastrointestinal stromal tumours. Various Protein tyrosine kinase inhibitors are available but face poor bioavailability, severe toxicities and recent cases of drug-resistant cancers prompts for development of better drug molecules. In this study we report the design and development of a novel Protein Tyrosine Kinase (PTK) inhibitor on the basis of pharmacophore modelling. Compound 2-(benzo[d]oxazol-2-ylamino)-N-(2-chloro-4-fluorophenyl)-4-methyl-6-(3-nitrophenyl) pyrimidine-5-carboxamide 31 was obtained containing essential pharmacophore structural features. This compound exhibited highest activity against leukaemia cell line (RPMI-8226) at 0.7244 µM, renal cancer cell line (A498) at 0.8511 µM and prostate cancer cell line (PC-3) at 0.7932 µM on the NCI five dose assay test. The PTK assay provides promising activity at IC50 of 0.07 µM in the human breast cancer cell line MDA-MB-468. Compound 31 had good intermolecular interaction with PTK in the molecular docking studies, this ligand-enzyme complex was found to stable in the MM-PBSA study over 100 ns. It had 54.22% oral bioavailability with Tmax of 0.60 h which is higher compared to the dasatinib with bioavailability and Tmax of 14–34% and 1–1.42 h respectively. Anticancer action of 31 was found to be impressive in pharmacokinetic studies making it a potential lead molecule.

Item Type: Article
Uncontrolled Keywords: sdg 3 - good health and well-being ,/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being
Faculty \ School: Faculty of Science > School of Pharmacy
Related URLs:
Depositing User: LivePure Connector
Date Deposited: 17 Aug 2020 23:54
Last Modified: 22 Oct 2022 06:25
DOI: 10.1016/j.bioorg.2018.01.008

Actions (login required)

View Item View Item