Work

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

Year: 2017

Type: article

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-1 H -pyrazole ( a ), 3-amino-(4E)-5-imino-1-[2-(6-methoxy-2-naphthyl)propanoyl]-4-(4-bromobenzylidene)-4,5-dihydro-1 H -pyrazole ( b ), 3-amino-(4E)-5-imino-1-[2-(6-methoxy-2-naphthyl)-propanoyl]-4-(4-methoxybenzylidene)-4,5-dihydro-1 H -pyrazole ( c ), 3-amino-(4E)-5-imino-1-[2-(6-methoxy-2-naphthyl)propanoyl]-4-(4-methylbenzylidene)-4,5-dihydro-1 H -pyrazole ( d ), 3-amino-(4E)-5-imino-1-[2-(6-methoxy-2-naphthyl)propanoyl]-4-(4-nitrobenzylidene)-4,5-dihydro-1 H -pyrazole ( e ) were synthesized then characterized by FTIR, 1 H and 13 C 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 (–NO 2 and –Br) and electron donating groups (–CH 3 and –OCH 3 ) 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 IC 50 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.

Source: Journal of King Saud University - Science

DOI: 10.1016/j.jksus.2017.01.003

Authors: Abdullah G. Al-Sehemi, Ahmad Irfan, Mohammad Alfaifi, Ahmed M. Fouda, Tarek Ma'mon El-Gogary, Diaa A. Ibrahim

Institutions: King Khalid University, Jazan University

Language: English

Topic: Synthesis and biological activity

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $1,600