Synthesis, cytotoxicity, and molecular docking of substituted 3‐(2‐methylbenzofuran‐3‐yl)‐5‐(phenoxymethyl)‐1, 2, 4‐oxadiazoles. Issue 6 (20th April 2020)

• Record Type: Journal Article
• Authors: Mokenapelli, Sudhakar; Thalari, Gangadhar; Vadiyaala, Naveen; Yerrabelli, Jayaprakash R.; Irlapati, Vamshi K.; Gorityala, Neelima; Sagurthi, Someswar R.; Chitneni, Prasad R.
• Is Part Of: Archiv der Pharmazie. Volume 353:Issue 6(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-04-20
• Subjects: 1, 2, 4‐oxadiazole -- benzofuran -- cytotoxicity -- docking studies -- glycogen synthase kinase‐3β; Pharmaceutical chemistry -- Periodicals; Pharmacology -- Periodicals; 615.19
• DOI: 10.1002/ardp.202000006
• Languages: English
• ISSNs: 0365-6233

Abstract

Abstract: A series of new benzofuran/oxadiazole hybrids (8a –n ) was synthesized from 2 H ‐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 (IC50 : 9.71 ± 1.9 μM), 6b (IC50 : 7.48 ± 0.6 μM), and 6c (IC50 : 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. Abstract : A series of new benzofuran/oxadiazole hybrids, known to exhibit anticancer activities, was synthesized, and these compounds were evaluated for their in vitro cytotoxicity against the HCT116 and MIA PaCa2 cell lines. Molecular docking of compounds 6a –c and 8d, e with GSK3β demonstrated the best binding affinity, correlating with the biological activity. The structure–activity relationship of these novel compounds reveals promising features for their use in anticancer therapy.