Novel sulfonamide derivatives carrying a biologically active 3,4-dimethoxyphenyl moiety as VEGFR-2 inhibitors

Ghorab, Mostafa Mohammed and Alsaid, Mansour Sulaiman and Nissan, Yassin Mohammed and Ashour, Abdelkader Elbadawy Abbas and Al-Mishari, Abdullah Abdulalrahman and Kumar, Ashok and Ahmed, Sheikh Fayaz (2016) Novel sulfonamide derivatives carrying a biologically active 3,4-dimethoxyphenyl moiety as VEGFR-2 inhibitors. Chemical and Pharmaceutical Bulletin, 64 (12). pp. 1747-1754. ISSN 0009-2363 E-ISSN 1347-5223

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Abstract

Novel sulfonamides 3-19 with a biologically active 3,4-dimethoxyphenyl moiety were designed and synthesized. The structures of the synthesized compounds were established using elemental analyses, IR, 1H-NMR, 13C-NMR spectral data and mass spectroscopy. All the synthesized compounds were evaluated for their in vitro anticancer activity against four cancer cell lines, namely human hepatocellular carcinoma (HepG2), human medulloblastoma (Daoy), human cervical cancer (HeLa), and human colon cancer (HT-29), by using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and dasatinib as the reference drug. Among the tested derivatives, compounds 4, 10, 16, and 19 showed good activity as cytotoxic agents. The most active derivatives were evaluated for their ability to inhibit vascular endothelial growth factor receptor (VEGFR)-2. Compounds Z-4-(3-(3,4-dimethoxyphenyl)-3-oxoprop-1-enylamino)-N-(5-methyl-1,3,4-thiadiazol-2-yl)-benzenesulfonamide 10 and Z-4-(3-(3,4-dimethoxyphenyl)-3-oxoprop-1-enylamino)-N-(1H-indazol-6-yl)-benzenesulfonamide 19 were more active as VEGFR-2 inhibitors than dasatinib. Molecular docking of the most active derivatives on the active site of VEGFR-2 revealed that compound 19 exhibited favorable and promising results.

Item Type:	Article (Journal)
Additional Information:	8129/64278
Uncontrolled Keywords:	growth factor receptor, benzenesulfonamide, 3,4-dimethoxyphenyl, anticancer
Subjects:	R Medicine > RM Therapeutics. Pharmacology > RM300 Drugs and their action
Kulliyyahs/Centres/Divisions/Institutes (Can select more than one option. Press CONTROL button):	Kulliyyah of Medicine > Department of Basic Medical Kulliyyah of Medicine
Depositing User:	Dr. Abdelkader Ashour
Date Deposited:	18 Jul 2018 09:57
Last Modified:	18 Jul 2018 09:57
URI:	http://irep.iium.edu.my/id/eprint/64278

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