Anti-Cancer Activity of Gabapentin and Chiral Amino Acids-Based Hybrid-Peptides against MCF-7 Breast Cancer Cell-Line

Bhavin M Vavaiya,Chandramani Pathak,Foram U Vaidya,Hitesh M Parekh,Jasmin B Padariya,Khushal M Kapadiya,Suryajitsinji L Rathod,Usha B Prajapati,Vraj B Pansuriya

doi:10.9734/jpri/2021/v33i46a32886

Abstract

Aims: Herein, we report the cytotoxicity of gabapentin-based peptides (11a-11j) using L-alanine and L-phenyl alanine chiral amino acids for peptide bond formation in ten efficient and straightforward steps. The in vitro MTT assays of derived molecules on the MCF-7 cell line (a human breast adenocarcinoma cell line) exhibited enhanced antitumor activity compared to the control (100% cell proliferation). Methods: The ten steps synthetic methods were adapted for the synthesis of the Gabapentin-based peptide derivatives through BOC- deBOC methods and using EDC-HCl, DMAP and commercially available solvents. All the synthesized peptides were unambiguously characterized with the help of spectroscopic (IR, 1H NMR, 13C-NMR, mass spectra, and elemental) data analysis. Results: The Compounds 11a, 11b, 11h,11i, and 11j showed a remarkable antiproliferative (cell death) activity, with % cell proliferation values ranging from 25-38 %. Conclusion: The study showed that the compounds with some specific functionalities like, benzylic and trifluoromethyl functionality enhanced the potency with comparable %cell proliferation and cell death. Based on the findings in this work and their easily accessible molecular structures, compounds 11a and 11j are worthy of further biological investigations.

Highlights

Cancer is reached at the top, threatening human health due to the increasing incidence and mortality
To extend our efforts towards promising anticancer agents using various natural/nonnatural precursors [48,49,50], we have reported a new class of Gabapentin base hybridpeptide derivatives (11a-11j) and were evaluated for anticancer screening against MCF-7 breast cancer cells line
The synthetic methods adapted for the synthesis of the Gabapentin-based peptide derivatives are represented in Scheme-1

Summary

Introduction

Cancer is reached at the top, threatening human health due to the increasing incidence and mortality. Among various types of cancers, breast cancer is one of the most common types among other malignancies in women and a significant cause of mortality worldwide [1,2]. New cases of breast cancer diagnosed in 2015 accounted for approximately 12% of all new malignancy cases, and mortality accounted for 25% of all cancer cases in women. The worldwide new cases of female breast cancer are estimated to reach nearly 3.2 million per year by 2050 [3,4,5]. Despite the intensive investigation of breast cancer cell lines, the cellular and molecular mechanisms between the MCF-7 cell line and the drug polyoxometalate (POM) are still limited [6]. Anticancer peptides (ACPs) have been proved to be effective small molecules (nearly 50 amino acids) that can act against cancerous cells by either a membranolytic mechanism or disruption of mitochondria [7]

Methods

Results

Conclusion