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

Bahare RS, Ganguly S, Choowongkomon K, Seetaha S - Daru (2015)

Bottom Line: Conformations of the structures were assigned on the basis of results of different spectral data.Some of the compounds have shown significant activity.Molecular docking studies showed very good interaction.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Sciences, Birla Institute of Technology, Mesra, Ranchi 835215, Jharkhand, India. radhe118@gmail.com.

ABSTRACT

Background: 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.

Methods: Title 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.

Results: The 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.

Conclusion: A 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.

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Pharmacophoric model of 2,4-thiazolidinedione analogs.
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Fig1: Pharmacophoric model of 2,4-thiazolidinedione analogs.

Mentions: Structural modifications of thiazolidinediones at 3rd and 5th position have exhibited significant biological activities [31]. In view of the mentioned above facts, and based on in silico studies carried out on thiazolidine 2,4-diones as HIV-1- RT inhibitors [32], a novel series of 2,4-thiazolidinedione analogs have been designed based on the pharmacophoric model of NNRTIs 18 with the thiazolidinedione moiety attached to the propionamide moiety (−CH2-CH2-CO-NH-) constituting the “body (hydrophilic)” flanked by aryl rings (hydrophobic) linked to the 3rd and 5th position of the thiazolidinedione ring and to that of substituted aromatic amines as the “wings” to enhance the hydrophobicity of the molecules (Figure 1).Figure 1


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

Bahare RS, Ganguly S, Choowongkomon K, Seetaha S - Daru (2015)

Pharmacophoric model of 2,4-thiazolidinedione analogs.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4308940&req=5

Fig1: Pharmacophoric model of 2,4-thiazolidinedione analogs.
Mentions: Structural modifications of thiazolidinediones at 3rd and 5th position have exhibited significant biological activities [31]. In view of the mentioned above facts, and based on in silico studies carried out on thiazolidine 2,4-diones as HIV-1- RT inhibitors [32], a novel series of 2,4-thiazolidinedione analogs have been designed based on the pharmacophoric model of NNRTIs 18 with the thiazolidinedione moiety attached to the propionamide moiety (−CH2-CH2-CO-NH-) constituting the “body (hydrophilic)” flanked by aryl rings (hydrophobic) linked to the 3rd and 5th position of the thiazolidinedione ring and to that of substituted aromatic amines as the “wings” to enhance the hydrophobicity of the molecules (Figure 1).Figure 1

Bottom Line: Conformations of the structures were assigned on the basis of results of different spectral data.Some of the compounds have shown significant activity.Molecular docking studies showed very good interaction.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Sciences, Birla Institute of Technology, Mesra, Ranchi 835215, Jharkhand, India. radhe118@gmail.com.

ABSTRACT

Background: 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.

Methods: Title 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.

Results: The 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.

Conclusion: A 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.

Show MeSH