Anti-Cancer Activity of Gabapentin and Chiral Amino Acids-Based Hybrid-Peptides against MCF-7 Breast Cancer Cell-Line
Vraj B. Pansuriya
Department of Chemistry, School of Sciences, Gujarat University, Ahmedabad 380009, Gujarat, India.
Khushal M. Kapadiya
Department of Chemistry, School of Science, RK University, Rajkot 360020, Gujarat, India.
Suryajitsinji L. Rathod
Department of Chemistry, School of Sciences, Gujarat University, Ahmedabad 380009, Gujarat, India.
Usha B. Prajapati
Department of Chemistry, School of Sciences, Gujarat University, Ahmedabad 380009, Gujarat, India.
Bhavin M. Vavaiya
Department of Chemistry, M. G. Science College, Gujarat University, Ahmedabad 380009, Gujarat, India.
Jasmin B. Padariya
Department of Chemistry, KSKV Kutch University, Bhuj 370001, Gujarat, India.
Foram U. Vaidya
Department of Cell Biology, School of Biological Sciences and Biotechnology, Indian Institute of Advanced Research, Gandhinagar 382426, Gujarat, India.
Chandramani Pathak
Department of Cell Biology, School of Biological Sciences and Biotechnology, Indian Institute of Advanced Research, Gandhinagar 382426, Gujarat, India.
Hitesh M. Parekh *
Department of Chemistry, School of Sciences, Gujarat University, Ahmedabad 380009, Gujarat, India.
*Author to whom correspondence should be addressed.
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.
Keywords: Peptide synthesis, gabapentin, l-alanine, l-phenyl alanine, antiproliferative activity, MCF-7 cell line