Synthesis and biological potentials of some new 1,3,4-oxadiazole analogues

Jawed Ahsan, Mohamed and Meena, Rachana and Dubey, Swati and Khan, Vasim and Manda, Sunita and Singh Jadav, Surender and Sharma, Piush and Geesi, Mohammed H. and Hassan, Mohd. Zaheen and Afroz Bakht, Mohammad and Riadi, Yassine and Akhter, Md. Habban and S, Salahuddin and Gundla, Rambabu (2018) Synthesis and biological potentials of some new 1,3,4-oxadiazole analogues. Medicinal Chemistry Research, 27 (3). pp. 864-883.


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Abstract|ملخص البحث

In continuation of our research to explore new antiproliferative agents, we report herein the synthesis and antiproliferative activity of two new series of N-(substituted phenyl)-5-aryl-1,3,4-oxadiazol-2-amine (4a--j) and N-{5-aryl-1,3,4-oxadiazol-2-ylmethyl{\}}-substituted aniline (4k--t) analogs. The antiproliferative activity of fifteen compounds (4a--h, and 4n) was tested against nine different panels of nearly 60 NCI human cancer cell lines. N-(2-Methoxyphenyl)-5-(4-chlorophenyl)-1,3,4-oxadiazol-2-amine (4b) and 4-{\{}5-(2-Methoxyphenyl)amino-1,3,4-oxadiazol-2-yl{\}}phenol (4c) showed maximum antiproliferative activity among the series with a mean growth percents (GPs) of 45.20 and 56.73, respectively. The compound 4b showed significant percent growth inhibitions (GIs) on nearly 47 cancer cell lines and were found to have higher sensitivity towards HL-60(TB), MDA-MB-435, OVCAR-3, and K-562 with percent GIs (GIs) of 109.62, 105.90, 91.94, and 88.30, respectively. Similarly the compound, 4c showed significant percent GIs on nearly 42 cancer cell lines and were found to have higher sensitivity towards UO-31, MDA-MB-435, KM12, and K-562 with {\%}GIs of 84.31, 80.52, 78.65, and 77.06, respectively. Both the compounds 4b and 4c showed better antiproliferative activity than the standard drug Imatinib while the antiproliferative activity of compound 4b was found to be nearly comparable to the standard drug 5-flurouracil (5-FU). The antiproliferative activity of five compounds (4o-s) was tested against the breast cancer cell lines (MCF-7 and MDA-MB-231) as per Sulforhodamine B assay (SRB assay). N-{\{}5-(4-Methoxyphenyl)-1,3,4-oxadiazol-2-ylmethyl{\}}-4-methylaniline (4p) was found to have significant antiproliferative activity against MCF-7 and MDA-MB-231 with GI50 of 12.9 and 59.3{\thinspace}{\textmu}M, respectively. Further, the free radical scavenging activity results were significant for the most active compounds, 4b (IC50{\thinspace}={\thinspace}21.07{\thinspace}{\textmu}M) and 4c (IC50{\thinspace}={\thinspace}15.58{\thinspace}{\textmu}M). The docking studies was also carried against tubulin enzyme and the most active compound (4b) showed good interaction with the residues Lys254, Ala250, Cys241, Val318, Ala316, Asn258, and Lys352 present in the hydrophobic cavity of tubulin.

Item Type|تصنيف النتاج العلمي: Article| منشور علمي
Subjects | مجال موضوع النشر: Chemistry
Pharmaceutical Sciences
Divisions | الكلية: College of Pharmacy > Pharmaceutical Sciences
Depositing User: Mohd. Zaheen Hassan
Date Deposited: 15 Apr 2018 05:16
Last Modified: 15 Apr 2018 05:16

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