Isatin thiazoline hybrids as dual inhibitors of HIV-1 reverse transcriptase

Rita Meleddu,Simona Distinto,Angela Corona,Enzo Tramontano,Giulia Bianco,Claudia Melis,Filippo Cottiglia,Elias Maccioni

doi:10.1080/14756366.2016.1238366

Abstract

A series of 3-3-{2-[2-3-methyl-4-phenyl-2,3-dihydro-1,3-thiazol-2-ylidene]hydrazin-1-ylidene-2,3-dihydro-1H-indol-2-one derivatives has been designed and synthesized to study their activity on both HIV-1 (Human Immunodeficiency Virus type 1) RT (Reverse Transcriptase) associated functions. These derivatives are analogs of previously reported series whose biological activity and mode of action have been investigated. In this work we investigated the influence of the introduction of a methyl group in the position 3 of the dihydrothiazole ring and of a chlorine atom in the position 5 of the isatin nucleus. The new synthesized compounds are active towards both DNA polymerase and ribonuclease H in the µM range. The nature of the aromatic group in the position 4 of the thiazole was relevant in determining the biological activity.

Highlights

HIV-1 (Human Immunodeficiency Virus type 1) is one of the major causes of death days
The current approved treatment is based on the highly active antiretroviral therapy (HAART), which associates a combination of antiviral agents, targeting different steps of the virus replication cycle[1,2,3]
This multidrug therapeutic regimen leads to the reduction of the amount of circulating virus, in some cases below the current blood testing techniques detectable level, and allows high control of the infection. It leads to the reduction of drug resistance occurrence, decrease of mortality and morbidity rates, and an overall improvement of patients quality of life[4]

Summary

Introduction

HIV-1 (Human Immunodeficiency Virus type 1) is one of the major causes of death days. The current approved treatment is based on the highly active antiretroviral therapy (HAART), which associates a combination of antiviral agents, targeting different steps of the virus replication cycle[1,2,3]. This multidrug therapeutic regimen leads to the reduction of the amount of circulating virus, in some cases below the current blood testing techniques detectable level, and allows high control of the infection. There is not a therapeutic regimen capable of completely eradicate the virus from the host and, due to the chronic nature of HIV infection, a lifelong therapy is required Both adherence to treatment and the management of drug-related toxicities are issues to deal with. In the light of the above the design and synthesis of new and more effective antiviral agents is an attractive open field for medicinal chemists

Methods

Results

Conclusion