In vitro Mechanistic Exploration of Novel Spiropyrrolidine Heterocyclic Hybrids as Anticancer Agents

Raju Suresh Kumar; Abdulrahman I Almansour; Natarajan Arumugam; Faruq Mohammad; Raju Ranjith Kumar

doi:10.3389/fchem.2020.00465

In vitro Mechanistic Exploration of Novel Spiropyrrolidine Heterocyclic Hybrids as Anticancer Agents

Front Chem. 2020 Jun 3:8:465. doi: 10.3389/fchem.2020.00465. eCollection 2020.

Authors

Raju Suresh Kumar¹, Abdulrahman I Almansour¹, Natarajan Arumugam¹, Faruq Mohammad¹, Raju Ranjith Kumar²

Affiliations

¹ Department of Chemistry, College of Science, King Saud University, Riyadh, Saudi Arabia.
² Department of Organic Chemistry, School of Chemistry, Madurai Kamaraj University, Madurai, India.

Abstract

Novel spiro acenaphthylene pyrrolo[1,2-b]isoquinoline/pyrrolidine hybrids have been achieved through Pictet-Spengler/Eschweiler-Clarke reactions depending on the substitution in the benzyl ring. The in vitro biological efficacy of N-methyl spiropyrrolidine derivatives toward different cancer and non-cancer cell lines revealed that these novel spiro heterocyclic hybrids induced cancer cell death at moderate concentrations, while slight reduction in non-cancer cell viability at the higher concentrations. The analysis of cancer cells proved that the major pathway of cell death is apoptosis and in addition, the role of caspases is confirmed by the appearance of fluorescent cells in microscopic images. Therefore, this study indicates a sustainable way of treating cancer cells by inducing apoptotic pathways and associated caspases, while simultaneously protecting the non-cancer cells.

Keywords: N-methylation; in vitro studies; molecular biology; role of caspases; spiropyrrolidine hybrid heterocycles.