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Anti-Cancer Agents in Medicinal Chemistry

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ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

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Research Article

Design, Synthesis, Anticancer Evaluation, and Molecular Docking Studies of Novel Benzoxazole Linked 1,3,4-Oxadiazoles

Author(s): Sushmitha Bujji, Edigi P. Kumar, Sree K. Sivan, D.H. Manjunatha and N.J.P. Subhashini*

Volume 22, Issue 5, 2022

Published on: 06 July, 2021

Page: [933 - 942] Pages: 10

DOI: 10.2174/1871520621666210706120203

Price: $65

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Abstract

Background: Cancer disease is a serious concern globally. Global cancer occurrence is steadily increasing every year. There is always a persistent need to develop new anticancer drugs with reduced side effects or that act synergistically with the existing chemotherapeutics.

Objective: Benzoxazoles are fused bicyclic nitrogen and oxygen-containing heterocyclic compounds and are considered biologically privileged scaffolds. We designed a synthetic route to link the benzoxazoles with oxadiazole,s resulting in a better pharmacophore for anticancer activity.

Methods: A series of novel amide derivatives of benzoxazole linked 1,3,4-oxadiazoles (10 a-j) were synthesized and characterized by 1H NMR, 13C NMR, and mass spectroscopic techniques. The biological properties of the compounds were screened in vitro against four different tumor cell lines.

Results: The results suggest that the compound 10b having 3,4,5-trimethoxy substitution on the phenyl ring exhibited potent anticancer activity in three cell lines (A549 = 0.13 ± 0.014 μM, MCF-7 = 0.10 ± 0.013 μM and HT-29 = 0.22 ± 0.017 μM). Notably, among the synthesized derivatives, compounds 10b, 10c, 10f, 10g, and 10i exhibited potent anticancer activity than the control, with IC50 values in the range from 0.11 ± 0.02 to 0.93 ± 0.034 μM. Molecular docking simulation results showed that compounds were stabilized by hydrogen bond and π-π interactions with the protein.

Conclusion: The molecules showed comparable binding affinities with standard Combretastatin-A4. The present research work is in a preliminary phase and needs further studies to take the synthesized compounds to the next level in the cancer research field.

Keywords: Benzoxazole, 1, 3, 4-oxadiazole, anticancer activity, cytotoxicity assays, molecular docking, combretastatin-A4.

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