Synthesis, cytotoxicity, and molecular docking of substituted 3-(2-methylbenzofuran-3-yl)-5-(phenoxymethyl)-1,2,4-oxadiazoles.

Autor: Mokenapelli S; Natural Products Laboratory, Department of Chemistry, Osmania University, Hyderabad, Telangana, India., Thalari G; Natural Products Laboratory, Department of Chemistry, Osmania University, Hyderabad, Telangana, India., Vadiyaala N; Natural Products Laboratory, Department of Chemistry, Osmania University, Hyderabad, Telangana, India., Yerrabelli JR; Natural Products Laboratory, Department of Chemistry, Osmania University, Hyderabad, Telangana, India., Irlapati VK; Department of Genetics and Biotechnology, Osmania University, Hyderabad, Telangana, India., Gorityala N; Department of Genetics and Biotechnology, Osmania University, Hyderabad, Telangana, India., Sagurthi SR; Department of Genetics and Biotechnology, Osmania University, Hyderabad, Telangana, India., Chitneni PR; Natural Products Laboratory, Department of Chemistry, Osmania University, Hyderabad, Telangana, India.
Jazyk: angličtina
Zdroj: Archiv der Pharmazie [Arch Pharm (Weinheim)] 2020 Jun; Vol. 353 (6), pp. e2000006. Date of Electronic Publication: 2020 Apr 20.
DOI: 10.1002/ardp.202000006
Abstrakt: A series of new benzofuran/oxadiazole hybrids (8a-n) was synthesized from 2H-chromene-3-carbonitriles (3a-c) through the multistep synthetic methodology, and these hybrids are known to exhibit anticancer activities. All the compounds were evaluated for their in vitro cytotoxicity against the HCT116 and MIA PaCa2 cell lines. Compounds 6a (IC 50 : 9.71 ± 1.9 μM), 6b (IC 50 : 7.48 ± 0.6 μM), and 6c (IC 50 : 3.27 ± 1.1 μM) displayed a significant cytotoxic activity, whereas compounds 8d and 8e exhibited good activity against both cell lines. The depletion of glycogen synthase kinase-3β (GSK3β) induces apoptosis through the inhibition of basal NF-κB activity in HCT116 colon cancer cells and MIA PaCa2 pancreatic cancer cells. Molecular docking of compounds 6a, 6b, 6c, 8d, and 8e with GSK3β demonstrated the best binding affinity, correlating with the biological activity assay. Furthermore, the structure-activity relationship of these novel compounds reveals promising features for their use in anticancer therapy.
(© 2020 Deutsche Pharmazeutische Gesellschaft.)
Databáze: MEDLINE
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