Classical QSAR Modeling of Anti-HIV 2,3-Diaryl-1,3-thiazolidin-4-ones

Abstract

Cytoprotection and cytotoxicity data of anti-HIV 2,3-diaryl-1,3-thiazolidin-4-ones were subjected to QSAR study using Fujita-Ban type analysis and a mixed approach based on Hansch and Fujita-Ban analyses. Apart from appropriate indicator and integer variables encoding different group contributions, different physicochemical variables like hydrophobicity (p) and steric (molar refractivity) parameters of aryl ring substituents of the compounds were used as predictor variables. Furthermore, Wang-Ford charges of the common atoms of the compounds calculated from molecular electrostatic potential surface of AM1 optimized geometries of the compounds and various topological parameters were used as additional descriptors. The variables for the multiple regression analyses were selected based on principal component factor analysis, and generated equations were statistically validated using leave-one-out technique and predicting the activity data of test set compounds. The statistical qualities of the equations for cytoprotection data (explained variance ranging 64.5 -80.3%, leave-one-out predicted variance ranging 44.3 -59.4%) are better than those for cytotoxicity data (explained variance ranging 59.7 -60.6%, leave-one-out predicted variance ranging 52.4 -54.4%). The analysis explores the structural and physicochemical requirements of the compounds for cytoprotection and cytotoxicity.

Recent Advances in the Research of 2,3-Diaryl-1,3-thiazolidin-4-one Derivatives as Potent HIV-1 Non-nucleoside Reverse Transcriptase Inhibitors

“…Interestingly, the replacement of 4'', 6''-dimethyl-pyrimidin-2''-yl by 2'', 6''-dimethyl-pyrimidin-4''-yl largely reduced the effectiveness, indicating that the electronic feature of the heterocycle must make great influence on the ability of inhibition. These results were in accordance with the prediction of a series of systematic QSAR studies [30][31][32], which suggested the significance in the hydrophobicity of the whole molecule, steric and electronic characters of meta-/para-substituents at N-3-aryl ring. It was also suggested that a heteroaryl system would be preferred at N-3 position for better HIV-1 RT inhibitory activity.…”

Design, synthesis and HIV-RT inhibitory activity of novel thiazolidin-4-one derivatives

“…Recently, 2,3-diaryl-1,3-thiazolidin-4-one scaffold has been reported to possess a selective inhibition against the HIV-1 reverse transcriptase (RT) by binding to the allosteric site of the enzyme as a non-nucleoside RT inhibitor (NNRTI) [10][11][12][13][14][15][16][17], and a high activity level was observed for compounds possessing a 4,5,6-trimethylpyrimidine moiety at N-3 position [18][19][20][21][22]. A systematic QSAR study revealed that the overall hydrophobicity of the molecule is important to enhance the anti-HIV activity [23][24][25][26][27][28]. Generally, extensive studies focused on the substitutions at the 2 and 3 position of thiazolidin-4-one [29][30][31].…”

Quantitative Structure–Activity Relationship Analysis of Some Thiourea Derivatives with Activities Against HIV‐1 (IIIB)

“…The Acquired Immunodeficiency Syndrome (AIDS) is a major and challenging health problem around the world for which no complete successful chemotherapy has been developed so far [1,2]. AIDS has been recognized as a fatal pathogenic disease caused by a retrovirus of the lentivirus family, Human Immunodeficiency Virus (HIV) [3].…”

“…The number of HIV-infected subjects keeps alarmingly on the rise [4,5]. The pandemic spread of this disease has prompted an unprecedented scientific and clinical effort to understand and combat it [2,6]. Intensive efforts have been madding worldwide to develop chemotherapeutic agents effective against the HIV infection [7].…”