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Synthesis of Some New Indole-1,3,4-Oxadiazole Hybrids as Tubulin Polymerization Inhibitors

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Abstract

We have synthesized some new molecular hybrids containing indole and 1,3,4-oxadiazole rings from the commercially available ethyl 1H-indole-2-carboxylate (I) in two steps using hydrazine hydrate and different aromatic carboxylic acids consecutively. All the hybrids were screened for the in vitro anticancer activity against SKOV3 (ovarian), A549 (lung) and MCF-7 (breast) cell lines using MTT assay and etoposide as the reference. The results revealed that the compound 2-(1H-indol-2-yl)-5-(4-methoxyphenyl)-1,3,4-oxadiazole (Vb) had superior potency against all the cell lines than the etoposide. As well, compounds 2-(3,5-dimethoxyphenyl)-5-(1H-indol-2-yl)-1,3,4-oxadiazole (Vc) and 4-(5-(1H-indol-2-yl)-1,3,4-oxadiazol-2-yl)benzonitrile (Vl) were found to have superior potency against MCF-7 cell line than the etoposide. The in vitro tubulin polymerization inhibitory assay of three active compounds (Vb), (Vc) and (Vl) revealed that the compounds (Vb) and (Vl) were shown double inhibiting power than standard combretastatin A-4. Finally, molecular docking studies of three active compounds (Vb), (Vc) and (Vl) towards α,β-tubulin also supported the corresponding in vitro activities.

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ACKNOWLEDGMENTS

The authors are thankful to the Department of Chemistry, Chaitanya (Deemed to be University) for providing Laboratory facilities.

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  1. Department of Chemistry, Chaitanya (Deemed to be University), 506001, Kishanpura, Hanumakonda, Telangana, India

    Sunitha Boda, Satheesh Kumar Nukala & Ravinder Manchal

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  1. Sunitha Boda
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  2. Satheesh Kumar Nukala
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Correspondence to Satheesh Kumar Nukala or Ravinder Manchal.

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Sunitha Boda, Nukala, S.K. & Manchal, R. Synthesis of Some New Indole-1,3,4-Oxadiazole Hybrids as Tubulin Polymerization Inhibitors. Russ J Bioorg Chem 48 (Suppl 1), S136–S143 (2022). https://doi.org/10.1134/S1068162023010077

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