Synthesis, HIV-1 RT inhibitory, antibacterial, antifungal and binding mode studies of some novel N-substituted 5-benzylidine-2,4-thiazolidinediones.

Radhe Shyam Bahare,Kiattawee Choowongkomon,Swastika Ganguly,Supaporn Seetaha

doi:10.1186/s40199-014-0086-1

Radhe Shyam Bahare, Kiattawee Choowongkomon + Show 2 more

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https://doi.org/10.1186/s40199-014-0086-1

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Abstract

BackgroundStructural modifications of thiazolidinediones at 3rd and 5th position have exhibited significant biological activities. In view of the facts, and based on in silico studies carried out on thiazolidine-2,4-diones as HIV-1- RT inhibitors, a novel series of 2,4-thiazolidinedione analogs have been designed and synthesized.MethodsTitle compounds were prepared by the reported method. Conformations of the structures were assigned on the basis of results of different spectral data. The assay of HIV-1 RT was done as reported by Silprasit et al. Antimicrobial activity was determined by two fold serial dilution method. Docking study was performed for the highest active compounds by using Glide 5.0.ResultsThe newly synthesized compounds were evaluated for their HIV-1 RT inhibitory activity. Among the synthesized compounds, compound 24 showed significant HIV-1 RT inhibitory activity with 73% of inhibition with an IC50 value of 1.31 μM. Compound 10 showed highest activity against all the bacterial strains.A molecular modeling study was carried out in order to investigate the possible interactions of the highest active compounds 24, 10 and 4 with the non nucleoside inhibitory binding pocket(NNIBP) of RT, active site of GlcN-6-P synthase and cytochrome P450 14-α-sterol demethylase from Candida albicans (Candida P450DM) as the target receptors respectively using the Extra Precision (XP) mode of Glide software.ConclusionA series of novel substituted 2-(5-benzylidene-2,4-dioxothiazolidin-3-yl)-N-(phenyl)propanamides (4–31) have been synthesized and evaluated for their HIV-1 RT inhibitory activity, antibacterial and antifungal activities. Some of the compounds have shown significant activity. Molecular docking studies showed very good interaction.

Highlights

Structural modifications of thiazolidinediones at 3rd and 5th position have exhibited significant biological activities
In the present study, a series of thiazolidinedione analogs have been synthesized and their structures have been characterized by IR, Proton Nuclear Magnetic Resonance (NMR) and mass spectroscopy
All the newly synthesized compounds were tested for Human Immuno Deficiency Virus (HIV)-1- reverse transcriptase (RT) inhibitory activity by microplate assay method and for antimicrobial activity by two fold serial dilution method

Summary

Introduction

Structural modifications of thiazolidinediones at 3rd and 5th position have exhibited significant biological activities. In view of the facts, and based on in silico studies carried out on thiazolidine-2,4-diones as HIV-1- RT inhibitors, a novel series of 2,4-thiazolidinedione analogs have been designed and synthesized. Compounds containing the thiazolidinedione moiety have been found to exhibit a wide range of biological activities viz., antihyperglycemic [3], anti-inflammatory [4], antimalarial [5], antioxidant [6], antitumor [7], cytotoxic [8], antimicrobial [9], antiproliferative [10], MurD ligase inhibitor [11], monoamine oxidase B (MAO-B) inhibitor [12] neuroprotective [13], COX-2 inhibitor [14] and chemotherapeutic activities [15]. The HIV infection targets the monocytes expressing surface CD4 receptors and produces profound defects in cell-mediated immunity [17]. Overtime infection leads to severe depletion of CD4 T-lymphocytes (T-cells) resulting in opportunistic infections like tuberculosis (TB), fungal, viral, protozoal and neoplastic diseases and death [18].

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