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Insights into the Structural Requirements of PKC β II Inhibitors Based on HQSAR and CoMSIA Analyses
Author(s) -
Kumar Hirdesh,
Kumar Rajendra,
Grewal Baljinder K.,
Sobhia M. Elizabeth
Publication year - 2011
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/j.1747-0285.2011.01144.x
Subject(s) - indole test , chemistry , pharmacology , protein kinase c , quantitative structure–activity relationship , stereochemistry , diabetic cardiomyopathy , small molecule , combinatorial chemistry , medicine , kinase , biochemistry , cardiomyopathy , heart failure
Diabetic cardiomyopathy is a clinical condition diagnosed when ventricular dysfunction develops in patients with diabetes devoid of coronary atherosclerosis and hypertension. The selective inhibition of PKC β II represents an effective approach for treating microvascular complications. HQSAR and CoMSIA studies were performed on a data set of 43 maleimide‐based molecules acting as potent inhibitors of PKC β II. HQSAR model yielded an of 0.98 and a cross‐validated of 0.85, while CoMSIA modeling of these same data generated an of 0.98 and a cross‐validated of 0.85. Both the models show good predictive power having for HQSAR and CoMSIA as 0.63 and 0.75, respectively, indicating the reliability of models. The analysis shows that the terminal substitution with electronegative atom at indole or azaindole ring is essential for PKC β II inhibition, while substitution of bulkier group in linker connecting two heteroaryl rings diminishes the activity. This study is presumably helpful in designing new potent molecules as PKC β II inhibitors in fighting against various diseases related to PKC β II.