Design, synthesis and anticancer activity of amide derivatives of substituted 3-methyl-benzofuran-2-carboxylic acid

Abstract

We have designed and synthesized amide derivatives of substituted 3-methyl-benzofuran-2-carboxylic acid with aryl sulfonamide piperazines, aryl hydrazides and aryl hydrazines. All the synthesized compounds were screened for their anticancer activity against lungs cancer cell line (A549) and breast cancer cell line (MCF7) using MTT assay. Compound 12b showed excellent activity against lungs cancer cell line (A549) with IC₅₀ value of 0.858 µM and compound 10d showed good activity against breast cancer cell line (MCF7) with IC₅₀ value of 2.07 µM. Hence, compounds 10d and 12b were studied further for their mechanism of cytotoxicity by using EtBr/AO and LDH assay in respective cell lines. The cytostatic potential of compound 10d and 12b was uncurtail by Trypan blue exclusion assay and active involvement of ROS was quantified using DCFH-DA dye. The drug-likeliness and toxicity predictions were done using in-silico-based SwissADME and ProTox-II webserver, which confirmed negligible toxicity (Class IV).

GRAPHICAL ABSTRACT

Keywords:

• Anticancer activity
• aryl sulfonamide piperazine
• benzofuran-2-carboxylic acid
• hydrazides
• benzofuran derivatives

Acknowledgments

Authors are thankful to The Head, Department of Chemistry and Department of Zoology, Faculty of Science, The M. S. University of Baroda for providing laboratory facilities, Zydus Research Centre, Ahmedabad, for the ESI-MS analyses. The authors are thankful to DST-FIST for NMR facility.

Additional information

Funding

One of the authors (JP) is thankful to Government of Gujarat for financial support vide reference [no. 202001720128] SHODH fellowship to carry out this work.