Multicomponent Domino Synthesis, Anticancer Activity and Molecular Modeling Simulation of Complex Dispirooxindolopyrrolidines.

Natarajan Arumugam,Rajapandian Krishnamoorthy,S Mahalingam,Shankar Thangamani,Raju Suresh Kumar,Abdulrahman Almansour,Vaiyapuri Periasamy,Periyasami Govindasami,Ali Alshatwi,Dhaifallah Al-Thamili,J Menéndez

doi:10.3390/molecules23051094

Abstract

A series of spirooxindolopyrrolidine fused N-styrylpiperidone heterocyclic hybrids has been synthesized in excellent yield via a domino multicomponent protocol that involves one-pot three component 1,3-dipolar cycloaddition and concomitant enamine reactions performed in an inexpensive ionic liquid, namely 1-butyl-3-methylimidazolium bromide ([bmim]Br). Compounds thus synthesized were evaluated for their cytotoxicity against U-937 tumor cells. Interestingly; compounds 5i and 5m exhibited a better cytotoxicity than the anticancer drug bleomycin. In addition; the effect of the synthesized compounds on the nuclear morphology of U937 FaDu cells revealed that treatment with compounds 5a–m led to their apoptotic cell death.

Highlights

The word “cancer” refers to a potentially lethal group of diseases characterized by unregulated proliferation and a dysregulation of apoptotic mechanisms
The results indicated that treatment with the compounds 5a–m caused more cells to take to apoptosis morphologies than necrotic features in dose and time-dependent manner
We have developed an environmentally benign domino one-pot multi-component synthesis of spiroheterocyclic hybrids in [bmim]Br

Summary

Introduction

The word “cancer” refers to a potentially lethal group of diseases characterized by unregulated proliferation and a dysregulation of apoptotic mechanisms. The development of resistance to chemotherapeutic agents and associated side effects are major obstacles to treat cancer effectively [1]. 22 of cytotoxicity, and both pathways are regulated by a group of proteases known as caspases [4]. Intrinsic mitochondrial pathwaydrugs [3], initiated by cytotoxicity, andstrategy both pathways are Targeting and thesethe pathways by chemotherapeutic is a proven therapeutic to control regulated by a group of proteases known as caspases [4]. Targeting these pathways by chemotherapeutic tumor growth and cancer progression [5]

Methods

Results

Conclusion