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Exploring the potential of newly synthesized 4-methyl-6-morpholino- pyrimidine derivatives as antiproliferative agents

Abstract

In view of exploring the potential of pyrimidine derivatives as anticancer agents, a series of 4-methyl-6-morpholinopyrimidine derivatives were synthesised and characterised by NMR (1H & 13C), SC-XRD and Mass spectral analysis. The in vitro anticancer activity of these compounds was investigated using different human cancer cell lines namely HeLa (cervix), NCI-H460 (lung), MCF-7(breast), HepG2 (liver) and IMR-32 (brain). Compounds 4c and 5h exhibited potent anticancer activity in dose dependent manner as compared to other derivatives, with an IC50 values of 5.88 ± 1.22 and 6.11± 2.12 µM on HeLa and NCI-H460 cells respectively. The inhibitory effect of 4c and 5h on cancer cell proliferation was shown to be a consequence of reactive oxygen species (ROS) generation and subsequent induction of cellular apoptosis, as evidenced by increase in hypodiploid (subG1) population, early apoptotic cell population, caspase-3/7 activity, loss of mitochondrial membrane potential and degradation of nuclear DNA. Furthermore, molecular docking studies revealed that 4c and 5h compounds binds to ATP binding pocket of mammalian target of rapamycin (mTOR). Based on our results we objectify that 4-methyl-6-morpholinopyrimidine derivatives prevent cancer cell proliferation by inducing apoptosis and thus have potential to be further explored for anticancer properties.

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Publication details

The article was received on 26 Oct 2017, accepted on 10 Jan 2018 and first published on 11 Jan 2018


Article type: Paper
DOI: 10.1039/C7NJ04157H
Citation: New J. Chem., 2018, Accepted Manuscript
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    Exploring the potential of newly synthesized 4-methyl-6-morpholino- pyrimidine derivatives as antiproliferative agents

    S. Gaonkar, M. A. Savanur, M. G. Sunagar, B. Puthusseri, N. Deshapande, A. A. Nadaf and I. A. M. Khazi, New J. Chem., 2018, Accepted Manuscript , DOI: 10.1039/C7NJ04157H

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