S. B. Katti

Carbodiimide mediated synthesis of 4-thiazolidinones by one-pot three-component condensation

In the present study, 4-thiazolidinones have been assembled by DCC mediated three-component reaction of amine, aldehyde and mercaptoacetic acid. The final compounds are obtained in quantitative yields within one hour.

Design and synthesis of 2-(2,6-dibromophenyl)-3-heteroaryl-1,3-thiazolidin-4-ones as anti-HIV agents.

A series of 2-(2,6-dibromophenyl)-3-heteroaryl-1,3-thiazolidin-4-ones were designed, synthesized and evaluated as selective human immunodeficiency virus type-1 reverse transcriptase (HIV-1 RT) enzyme inhibitors. The results of the HIV-1 RT kit and in vitro cell based assay showed that eight compounds effectively inhibited HIV-1 replication at 20-320 nM concentrations with minimal cytotoxicity in MT-4 as well as in CEM cells.

An expeditious synthesis of thiazolidinones and tetathiazanones

In the present study, 4-thiazolidinones have been assembled by HBTU mediated three-component reaction of amine, aldehyde and mercapto acid derivatives at room temperature. The final compounds are obtained in excellent yields within 30 minutes.

Topological descriptors in modeling the HIV inhibitory activity of 2-aryl-3-pyridyl-thiazolidin-4-ones.

The HIV-1 RT inhibitory activity of 2-(2,6-dihalophenyl)-3-(substituted pyridin-2-yl)-thiazolidin-4-ones has been analyzed with different topological descriptors obtained from DRAGON software. Here, simple topological descriptors (TOPO), Galvez topological charge indices (GVZ) and 2D autocorrelation descriptors (2DAUTO) have been found to yield good predictive models for the activity of these compounds. The correlations obtained from the TOPO class descriptors suggest that less extended or compact saturated structural templates would be better for the activity. The participating GVZ class descriptors suggest that they have same degree of influence on the activity. In 2DAUTO class, the large participation of descriptors of lags seven and three indicate the association of activity information with the seven and three centered structural fragments of these compounds. The physicochemical weighting components of these descriptors suggest homogeneous influence of mass, volume, electronegativity and/ or polarizability on the activity.

CoMFA and CoMSIA studies on thiazolidin-4-one as anti-HIV-1 agents

Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were performed on thiazolidin-4-one class of compounds as HIV-1 reverse transcriptase (HIV-1 RT) inhibitors using global minima and crystal structure conformations. Results obtained from the crystal structure-based model yielded superior statistical data (r(cv)(2) values of 0.683 for CoMFA and 0.678 for CoMSIA) when compared to those obtained by the global minima-based model (r(cv)(2) values of 0.625 and 0.654 for CoMFA and CoMSIA, respectively). The models were validated using an external test set of 47 compounds. The predictive r(2) values for the crystal-based CoMFA and CoMSIA models were 0.735 and 0.739, respectively, while the corresponding predictive r(2) values for the global minima-based CoMFA and CoMSIA models were 0.654 and 0.635, respectively. 3D contour maps generated from these models provide the regions in space where interactive fields may influence the activity. The superimposition of contour maps on the active site of HIV-1 reverse transcriptase additionally helped in understanding the structural requirements of these inhibitors. The results provide insight for predictive and diagnostic aspects of this class of HIV-1 RT inhibitors for better activity.

4-Aminoquinoline derived antimalarials: Synthesis, antiplasmodial activity and heme polymerization inhibition studies

A new series of 4-aminoquinoline derivatives have been synthesized and found to be active against both susceptible and resistant strains of Plasmodium falciparum in vitro. Compound 1-[3-(7-chloro-quinolin-4-ylamino)-propyl]-3-cyclopropyl-thiourea (7) exhibited superior in vitro activity against resistant strains of P. falciparum as compared to chloroquine (CQ). All the compounds showed resistance factor between 0.59 and 4.31 as against 5.05 for CQ. Spectroscopic studies suggested that this class of compounds act on heme polymerization target.

Non-nucleoside inhibitors of the hepatitis C virus NS5B RNA-dependant RNA polymerase: 2-Aryl-3-heteroaryl-1,3-thiazolidin-4-one derivatives

Hepatitis C virus (HCV) NS5B RNA polymerase is crucial for replicating the HCV RNA genome and is an attractive target for developing anti-HCV drugs. A novel series of 2,3-diaryl-1,3-thiazolidin-4-one derivatives were evaluated for their ability to inhibit HCV NS5B. Of this series, compounds 4c, 5b, 5c and 6 emerged as more potent, displaying over 95% inhibition of NS5B RNA polymerase activity in vitro. The two most active compounds 4c and 5c exhibited an IC(50) of 31.9 microM and 32.2 microM, respectively, against HCV NS5B.

Synthesis and QSAR Studies on Thiazolidinones as Anti-HIV Agents

Selected 4-thiazolidinone have been synthesized and tested as anti-HIV activity. The results of the in vitro tests showed that one of the compounds, 5, inhibited the enzyme at 0.204 microM concentration with minimal toxicity to MT-4 cell. Furthermore, the QSAR studies indicated the role of PMIZ, Ovality and Total energy content of the compounds in rationalizing the activity.

Synthesis and Biological Evaluation of 2, 3-Diaryl substituted-1, 3-thiazolidin-4-ones as Anti-HIV Agents

A series of 1,3-thiazolidin-4-ones and metathiazanones were synthesized and evaluated as anti-HIV agents. The results of the in vitro assays showed that some of the synthesized compounds were effective inhibitor of reverse transcriptase enzyme of human immunodeficiency virus type-1 (HIV-1) at micromolar concentrations with less cytotoxicity in MT-4 cells as compared to thiazolobenzimidazole (TBZ). Structure-activity relationship studies revealed that the nature of the substituents at the 2 and 3 positions of the thiazolidin-4-one nucleus had a significant impact on the in vitro anti-HIV activity of this class of antiretroviral agents. One of the compounds, 1, inhibited the enzyme at 0.204 microM concentrations with minimal cytotoxicity to MT-4 cells.

2‐(2,6‐Dihalo‐phenyl)‐3‐heteroaryl‐2‐ylmethyl‐1, 3‐thiazolidin‐4‐ones: Anti‐HIV agents

A diversity of novel 2‐aryl‐3‐heteroaryl‐2‐ylmethyl‐1,3‐thiazolidin‐4‐ones were designed and synthesized by reacting heteroaryl‐2‐ylmethyl amine with various 2,6‐dihalosubstituted benzaldehydes and mercaptoacetic acid. The title compounds were evaluated for human immunodeficiency virus type‐1 (HIV‐1) reverse transcriptase (RT) inhibitory activity. The results of in vitro assays showed that some of the compounds were effective inhibitors of HIV‐1 reverse transcriptase enzyme at micromolar concentrations with less cytotoxicity in both MT‐4 cells as well as acutely infected human T‐lymphoid CEM cells. Compounds 4h and 4k emerged as moderately more potent with EC50 are at 0.20 and 0.21 μm as compared to reference parent compound thiazolobenzimidazoles EC50 0.35 μm in MT‐4 cells.