Computational study and in vitro evaluation of the anti-proliferative activity of novel naproxen derivatives
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-me...
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Elsevier
2017-07-01
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| Series: | Journal of King Saud University: Science |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1018364716304943 |
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| author | Abdullah G. Al-Sehemi Ahmad Irfan Mohammad Alfaifi Ahmed M. Fouda Tarek Ma'mon El-Gogary Diaa A. Ibrahim |
| author_facet | Abdullah G. Al-Sehemi Ahmad Irfan Mohammad Alfaifi Ahmed M. Fouda Tarek Ma'mon El-Gogary Diaa A. Ibrahim |
| author_sort | Abdullah G. Al-Sehemi |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-11T00:08:20Z |
| format | Article |
| id | doaj.art-f2915e7bb8b74bbf8d8ef288370e1b56 |
| institution | Directory Open Access Journal |
| issn | 1018-3647 |
| language | English |
| last_indexed | 2024-12-11T00:08:20Z |
| publishDate | 2017-07-01 |
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| series | Journal of King Saud University: Science |
| spelling | doaj.art-f2915e7bb8b74bbf8d8ef288370e1b562022-12-22T01:28:15ZengElsevierJournal of King Saud University: Science1018-36472017-07-0129331131910.1016/j.jksus.2017.01.003Computational study and in vitro evaluation of the anti-proliferative activity of novel naproxen derivativesAbdullah G. Al-Sehemi0Ahmad Irfan1Mohammad Alfaifi2Ahmed M. Fouda3Tarek Ma'mon El-Gogary4Diaa A. Ibrahim5Department of Chemistry, Faculty of Science, King Khalid University, Abha 61413, P.O. Box 9004, Saudi ArabiaDepartment of Chemistry, Faculty of Science, King Khalid University, Abha 61413, P.O. Box 9004, Saudi ArabiaDepartment of Biology, Faculty of Science, King Khalid University, Abha 61413, P.O. Box 9004, Saudi ArabiaDepartment of Chemistry, Faculty of Science, King Khalid University, Abha 61413, P.O. Box 9004, Saudi ArabiaFaculty of Science, Jazan University, Jazan, Saudi ArabiaFaculty of Science, Jazan University, Jazan, Saudi ArabiaIn 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.http://www.sciencedirect.com/science/article/pii/S1018364716304943Biological active compoundsNaproxen derivativesQuantitative structure–activity relationshipElectro-optical propertiesAntiproliferative activity |
| spellingShingle | Abdullah G. Al-Sehemi Ahmad Irfan Mohammad Alfaifi Ahmed M. Fouda Tarek Ma'mon El-Gogary Diaa A. Ibrahim Computational study and in vitro evaluation of the anti-proliferative activity of novel naproxen derivatives Journal of King Saud University: Science Biological active compounds Naproxen derivatives Quantitative structure–activity relationship Electro-optical properties Antiproliferative activity |
| title | Computational study and in vitro evaluation of the anti-proliferative activity of novel naproxen derivatives |
| title_full | Computational study and in vitro evaluation of the anti-proliferative activity of novel naproxen derivatives |
| title_fullStr | Computational study and in vitro evaluation of the anti-proliferative activity of novel naproxen derivatives |
| title_full_unstemmed | Computational study and in vitro evaluation of the anti-proliferative activity of novel naproxen derivatives |
| title_short | Computational study and in vitro evaluation of the anti-proliferative activity of novel naproxen derivatives |
| title_sort | computational study and in vitro evaluation of the anti proliferative activity of novel naproxen derivatives |
| topic | Biological active compounds Naproxen derivatives Quantitative structure–activity relationship Electro-optical properties Antiproliferative activity |
| url | http://www.sciencedirect.com/science/article/pii/S1018364716304943 |
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