Design, synthesis and biological evaluation of 2-(phenoxymethyl)-5-phenyl-1,3,4-oxadiazole derivatives as anti-breast cancer agents

• Published in: European journal of medicinal chemistry Vol. 168; pp. 1 - 10
• Main Authors: Lakshmithendral, K., Saravanan, K., Elancheran, R., Archana, K., Manikandan, N., Arjun, H.A., Ramanathan, M., Lokanath, N.K., Kabilan, S.
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 15-04-2019
• Subjects: 1,3,4-Oxadiazoles; Breast cancer; Estrogen receptor; Molecular docking; Estrogen receptor; 1,3,4-Oxadiazoles; Breast cancer; Molecular docking
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2019.02.033

Structural based molecular docking approach revealed the findings of 2-(phenoxymethyl) -5-phenyl-1,3,4-oxadiazole derivatives. The compounds (7a-o) were synthesized and characterized well by using conventional methods. The compounds, 7b and 7m were reconfirmed through single crystal XRD analysis. The synthesized compounds (7a-o) were evaluated their antiproliferative activities against MCF-7 and MDA-MB-453. Furthermore, Lipinski's rule of five and pharmacokinetic properties were predicted for the test compounds. These results demonstrate that the compounds 7b and 7d exhibit more potent cytotoxicity and 7d exhibits dose-dependent activity and reduced cell viability. Further, the mechanism of action for the induced apoptosis was observed through morphological changes and western blotting analysis. These findings may furnish the lead for further development.
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•15 new compounds with 1,3,4-oxadiazole scaffolds were designed and synthesized.•The compounds, 7b and 7m were reconfirmed through single crystal XRD analysis.•The morphological changes and induced apoptosis in TNBC were observed after the treatment with the compound, 7d.