Synthesis, Biological Evaluation and Molecular Docking Studies Against EGFR Tyrosine Kinase of 3,5-bis(substituted benzylidene)-1- ethylpiperidin-4-one Analogues

Title:Synthesis, Biological Evaluation and Molecular Docking Studies Against EGFR Tyrosine Kinase of 3,5-bis(substituted benzylidene)-1- ethylpiperidin-4-one Analogues

Volume: 18 Issue: 9

Author(s): Mohamed Jawed Ahsan*, Deepak Saini, Piush Sharma, Surender Singh Jadav, Mohammad Afroz Bakht, Salahuddin, Ramesh Alluri and Md Faiyazuddin

Affiliation:

• Department of Pharmaceutical Chemistry, Maharishi Arvind College of Pharmacy, Ambabari Circle, Jaipur, Rajasthan 302 039,India

Keywords: Anticancer, Antioxidant, EGFR tyrosine kinase, Piperidone, α, β-Unsaturated ketone.

Abstract:

Cancer is one of the leading causes of death. The aim of the present study was to synthesize and investigate the anticancer and antioxidant activities of some 3,5-bis(substituted benzylidene)- 1-ethylpiperidin-4-one analogues (4a-g).

The 3,5-bis(substituted benzylidene)-1-ethylpiperidin-4-one analogues (4a-g) were prepared from the precursor, piperidin-4-one hydrochloride (1). The initial step involved the synthesis of intermediates, 3,5-bis(substituted benzylidene)piperidin-4-one analogues (3a-g) followed by their ethylation with C₂H₅I in acetone and K₂CO₃ to obtain the title compounds (4a-g). The Fourier transform infrared (FTIR), nuclear magnetic resonance (¹H & ¹³C NMR), mass spectrometry and microanalysis were used to characterize the title compounds (4a-g). All the compounds were further evaluated for their anticancer activity by SRB assay and NCI US protocol, while the antioxidant activity was evaluated by DPPH free radical assay. All the title compounds (4a-g) were subjected to molecular docking studies against EGRF tyrosine kinase, a potential target for anticancer agents, to study the possible mode of interaction of our compounds with the molecular target.

The compound 4g showed significant anticancer activity with GI₅₀ of 28.2 μM against MCF-7 (Breast cancer cell line). The antioxidant activity of compound 4g (IC₅₀ = 14.98±0.91 μM) was found to be comparable to the standard drug ascorbic acid. The binding modes of compounds 4a-g against the molecular target EGFR tyrosine kinase were also studied. The structure-activity relationship (SAR) was also studied.

The compound 4g showed significant anticancer activity with GI₅₀ of 28.2 μM against MCF-7 (Breast cancer cell line). The antioxidant activity of the compound, 4g was found to be comparable to the standard drug ascorbic acid, while its anticancer activity was found to be less than that of the standard drug adriamycin.

Cite this article as:

Ahsan Jawed Mohamed *, Saini Deepak , Sharma Piush , Jadav Singh Surender , Bakht Afroz Mohammad , Salahuddin , Alluri Ramesh and Faiyazuddin Md , Synthesis, Biological Evaluation and Molecular Docking Studies Against EGFR Tyrosine Kinase of 3,5-bis(substituted benzylidene)-1- ethylpiperidin-4-one Analogues, Letters in Organic Chemistry 2021; 18 (9) . https://dx.doi.org/10.2174/1570178617999201020220400