Computational study and in vitro evaluation of the anti-proliferative activity of novel naproxen derivatives

2Citations
Citations of this article
10Readers
Mendeley users who have this article in their library.

Abstract

In the present work, five naproxen derivatives, i.e., 3-amino-(4E)-5-imino-1-[2-(6-methoxy-2-naphthyl)propanoyl]-4-(benzylidene)-4,5-dihydro-1H-pyrazole (a), 3-amino-(4E)-5-imino-1-[2-(6-methoxy-2-naphthyl)propanoyl]-4-(4-bromobenzylidene)-4,5-dihydro-1H-pyrazole (b), 3-amino-(4E)-5-imino-1-[2-(6-methoxy-2-naphthyl)-propanoyl]-4-(4-methoxybenzylidene)-4,5-dihydro-1H-pyrazole (c), 3-amino-(4E)-5-imino-1-[2-(6-methoxy-2-naphthyl)propanoyl]-4-(4-methylbenzylidene)-4,5-dihydro-1H-pyrazole (d), 3-amino-(4E)-5-imino-1-[2-(6-methoxy-2-naphthyl)propanoyl]-4-(4-nitrobenzylidene)-4,5-dihydro-1H-pyrazole (e) were synthesized then characterized by FTIR, 1H and 13C NMR techniques. The ground state geometries were optimized by B3LYP functional of density functional theory (DFT) with three different basis sets (6-31G∗, 6-31G∗∗ and 6-31+G∗∗). The absorption wavelengths, oscillator strengths and major transitions were calculated using time dependent DFT. The effect of electron withdrawing groups (–NO2 and –Br) and electron donating groups (–CH3 and –OCH3) was intensively studied with respect to structure–activity relationship (SAR), quantitative structure–activity relationship (QSAR), frontier molecular orbitals (FMOs), molecular electrostatic potentials (MEP) and global reactivity descriptors. By the analysis of molecular docking work, it was found that pure hydrophobic substitution at position 4 of aldehyde part is more favorable than hydrophilic one. Compound c showed strong anti-proliferative activity against MCF-7 cells with IC50 value of 1.49 μM, and compound d showed moderate activity. The docking studies revealed that normal alkane chain is improving the biological activity in compound c, which endorsed to bury well in the active site resulting to enhance the hydrophobic interactions. The newly synthesized compounds against tested cell lines showed stronger antiproliferative activity as compared to the naproxen.

Cite

CITATION STYLE

APA

Al-Sehemi, A. G., Irfan, A., Alfaifi, M., Fouda, A. M., Ma’mon El-Gogary, T., & Ibrahim, D. A. (2017). Computational study and in vitro evaluation of the anti-proliferative activity of novel naproxen derivatives. Journal of King Saud University - Science, 29(3), 311–319. https://doi.org/10.1016/j.jksus.2017.01.003

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free