Application of the Triazolization Reaction to Afford Dihydroartemisinin Derivatives with Anti-HIV Activity.

Sampad Jana,Wim Dehaen,Shabina Iram,Muhammad Hayat,Christophe Pannecouque,Joice Thomas

doi:10.3390/molecules22020303

Abstract

Artemisinin and synthetic derivatives of dihydroartemisinin are known to possess various biological activities. Post-functionalization of dihydroartemisinin with triazole heterocycles has been proven to lead to enhanced therapeutic potential. By using our newly developed triazolization strategy, a library of unexplored fused and 1,5-disubstituted 1,2,3-triazole derivatives of dihydroartemisinin were synthesized in a single step. All these newly synthesized compounds were characterized and evaluated for their anti-HIV (Human Immunodeficiency Virus) potential in MT-4 cells. Interestingly; three of the synthesized triazole derivatives of dihydroartemisinin showed activities with half maximal inhibitory concentration (IC50) values ranging from 1.34 to 2.65 µM.

Highlights

The human immunodeficiency virus (HIV), the causative agent of the acquired immunodeficiency syndrome (AIDS), has been plaguing the human race for more than thirty years [1]
A series of newly functionalized artemisinin derivatives has been prepared by using a organocatalytic multicomponent reaction
The starting precursors 5 and 9 were used for triazolization reactions resulting in the formation of fused and 1,5-disubstituted 1,2,3-triazole derivatives

Summary

Introduction

The human immunodeficiency virus (HIV), the causative agent of the acquired immunodeficiency syndrome (AIDS), has been plaguing the human race for more than thirty years [1]. Even though more than thirty drugs targeting different steps of the viral life cycle are either approved or in clinical stages to treat HIV/AIDS [2], a cure remains elusive. Emergence of HIV strains that are no longer sensitive to the drug cocktails employed is leading to inability to completely block the viral replication [3]. Finding new anti-HIV agents that are less toxic and more effective in targeting HIV reservoirs in the body is still needed. Artemisinin has been used successfully at nanomolar concentrations against both chloroquine-sensitive and -resistant strains of Plasmodium falciparum. Reduction of the carbonyl group of artemisinin leads to the synthesis of dihydroartemisinin in high yields without disrupting the unusual peroxide linkage of artemisinin which has in turn lead to the development of a series of semi-synthetic first generation derivatives including the oil soluble artemether and arteether, and water soluble sodium

Methods

Results

Conclusion