Abstract
Some novel anthranilate diamides derivatives 4a–e, 6a–c and 9a–d were designed and synthesized to be evaluated for their in vitro anticancer activity. Structures of all newly synthesized compounds were confirmed by infra-red (IR), high-resolution mass (HR-MS) spectra, 1H nuclear magnetic resonance (NMR) and 13C nuclear magnetic resonance (NMR) analyses. Cytotoxic screening was performed according to (3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide) tetrazolium (MTT) assay method using erlotinib as a reference drug against two different types of breast cancer cells. The molecular docking study was performed for representative compounds against two targets, epidermal growth factor receptor (EGFR) and tubulin in colchicine binding site to assess their binding affinities in order to rationalize their anticancer activity in a qualitative way. The data obtained from the molecular modeling was correlated with that obtained from the biological screening. These data showed considerable anticancer activity for these newly synthesized compounds. Biological data for most of the anthranilate diamide showed excellent activity with nanomolar or sub nanomolar half maximal inhibitory concentration (IC50) values against tumor cells. EGFR tyrosine kinase (TK) inhibition assay, tubulin inhibition assay and apoptosis analysis were performed for selected compounds to get more details about their mechanism of action. Extensive structure activity relationship (SAR) analyses were also carried out.
Highlights
Cancer represents a major health problem and afflicts millions of people worldwide [1,2]
As the target compounds had potent antiproliferative activity, in vitro epidermal growth factor receptor (EGFR) inhibition capability was firstly performed for selective compounds (4b), (6a), (6c), (9a) and (9b) to see whether their cytotoxicity was mediated by kinase inhibition comparing to the reference staurosporine
We have designed some new derivatives of n-furoyl anthranilate and evaluated their cytotoxicities in vitro against a panel of two different cancer cell lines
Summary
Cancer represents a major health problem and afflicts millions of people worldwide [1,2]. There is a vital need for discovery and development of a new class of anticancer drugs with special characteristics that are not currently used. The disappearance of the amino hydrazide protons and appearance of one singlet characteristic for the imine proton H–C=N at 8.5 ppm was a clear evidence for the formation of Schiff bases 9a–d. In their 13C NMR spectra, the imine carbon H–C=N appeared in the downfield region at 146.6 ppm
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