In silico and in vitro investigation of anticancer effect of newly synthesized nonivamide-s-allyl cysteine ester

Abstract

Nonivamide (NOV), less pungent analogue of capsaicin present in various Capsicum species is known for various biological properties. S-allyl cysteine (SAC) abundantly present in aged garlic extract is gaining importance for anticancer property. NOV was esterified with SAC to increase the biological activity. In silico ADME analysis revealed the drug-likeness of NOV-SAC. Molecular docking and dynamics simulation analysis were done to understand the interaction of NOV-SAC with therapeutic target proteins (human estrogen receptor α, tumo protein negative regulator mouse double minute 2, B-cell lymphoma 2 and cyclin-dependent kinase 2) to treat cancer. NOV-SAC interacted with these proteins stably with favorable binding energy which was calculated through MMGBSA method. In line with in silico results, NOV-SAC showed antiproliferative activity against breast cancer cell line (MCF-7). NOV-SAC treatment increased ROS generation, decreased the antioxidant level, arrested cells at G1/S phase, disrupted mitochondrial membrane potential and initiated DNA fragmentation. The expression of p53 is increased by NOV-SAC treatment, in concordance the ratio of Bcl-2/Bax was decreased. Altogether, NOV-SAC was synthesized for the first time and it induced apoptosis in MCF-7 cells through triggering ROS generation and increasing the expression of p53. The in silico results has been mirrored in in vitro analysis of NOV-SAC against cancer cell line.

Communicated by Ramaswamy H. Sarma

Keywords:

• Nonivamide
• s-allyl cysteine
• anticancer
• oxidative stress
• apoptosis
• p53

Acknowledgements

Mrs. V. Sudha acknowledges Periyar University for the award of University Research Fellowship. Dr. L. Chitra acknowledges University Grants Commission, India for the award of Dr. D.S. Kothari Post-Doctoral Fellowship (Ref. No. F.4-2/2006 (BSR)/BL/17-18/0313). Dr. S. Penislusshiyan acknowledges Human Resource Development, Department of Health Research, Ministry of Health and Family Welfare, India for the award of young scientist fellowship (Ref. No. R.12014/51/2020-HR). The authors thank the Department of Computer Science, Periyar University for providing the High-performance computer facility.

Disclosure statement

All authors declare no conflict of interest.