Interaction of memantine with calf thymus DNA: an in-vitro and in-silico approach and cytotoxic effect on the cancerous cell lines

Abstract

Memantine belongs to the class of cognition enhancers that functions as NMDA receptor antagonist, used to treat Alzheimer's disease. The interaction of memantine with DNA was not investigated. In the present study, the interaction of memantine with ct-DNA, as well as its cytotoxicity on cancer cells, was evaluated. UV-visible spectroscopy, steady-state fluorescence spectroscopic studies revealed the interaction between memantine and ct-DNA. The quenching studies, chemical denaturation, (CD), and DNA melting studies showed the groove binding mode of memantine with ct-DNA. The thermodynamic parameters revealed that the interaction between memantine and ct-DNA is enthalpically driven, and the stabilizing forces involved were hydrogen bonding and van der Waals interaction. The groove-binding was also observed by molecular docking studies, which corroborated the findings of spectroscopic investigations. Density function theory calculations confirmed the existence of electron donor and recipient groups. The stability of memantine and DNA interaction, as well as the critical residues involved in the interaction, was identified by molecular dynamics simulations. Memantine showed cytotoxicity towards the cancer cells as compared to normal cells, as observed by MTT assay. Inverted compound microscopy analysis of memantine treated cancer cell lines further confirmed the results obtained by MTT assay.

Communicated by Ramaswamy H. Sarma

Keywords:

• Memantine
• ct-DNA
• spectroscopy
• molecular dynamics simulation
• cytotoxicity

Acknowledgements

We are thankful to the CSIR, New Delhi for providing SRF to FA, DST-INSPIRE SRF to SS, and N-PDF (File PDF/2016/00492) by DST-SERB to TS. We are also thankful to the UGC-DRS-SAP, DST-FIST and DST-PURSE for generous funding to the Department of Biochemistry, Faculty of Life Sciences and BRAF at C-DAC, Pune for providing supercomputer facility to carry out MD simulations.

Disclosure statement

The authors declare that there is no conflict of interest in this work.

Authors Contribution

Faisal Ameen: Writing- Original draft preparation, Conceptualization, Methodology, Formal analysis, Software, Validation Sharmin Siddiqui: Writing - Review & Editing, Software, Formal analysis Tarique Sarwar: Methodology, Writing Tasneem Kausar: Software Shahid M. Nayeem: Software Sayeed ur Rehman: Writing - Review & Editing and Mohammad Tabish: Supervision