Computational Study of 2-Aminothiazole as Antiprion Lead Com | 43944

International Journal of Pharmacy Teaching & Practices

ISSN - 1986-8111


Computational Study of 2-Aminothiazole as Antiprion Lead Compound in the Treatment of Creutzfeldt-Jakob Disease Using an Approach Model of Hansch Quantitatif Structure Activity Relationship and Toxicity Prediction

Deden Indra Dinata, Rika Rendrika, Hendy Pryanda

Objective. Creutzfeldt-Jakob Disease (CJD) is a rare, degenerative, invariably fatal brain disorder. It affects about one person in every one million people per year worldwide. CJD usually appears in later life and runs a rapid course. Typically, onset of symptoms occurs about age 60, and about 90 percent of individuals die within 1 year. The first symptom of CJD is rapidly progressive dementia leading to memory loss, personality changes and hallucinations. Prions are infectious proteins that cause brain disorders like Mad Cow Disease and Creutzfeldt-Jakob Disease in humans. A computational study of quantitative structure activity relationship (QSAR) and toxicity prediction of 2-aminothiazole as an antiprion lead compounds in the treatment of Creutzfeldt-Jakob disease has done. Method. computational method using an approach model of Hansch-QSAR and ADMET Predictor. Increasing the concentration of 2-aminothiazole in the brain used model approach to Hansch-QSAR by varying physicochemical properties such as log P values, Homo-Lumo Energy and Molecular Refraction (MR). parameters were then used as descriptors for determining mathematical models that describe the quantitative structure activity relationship of 2-aminothiazole using linear regression, a statistical model of parabolic regression and multiple regression to obtained the conclusion. Result. The results proved that derivates compound of 2-aminothiazole as a potential antiprion. 2-aminothiazole compounds leads to potentially therapeutic antiprion Creutzfeldt–Jakob disease with separating the abnormal prions directly and inhibits the formation of abnormal prions. Steric (MR) and Lipophilic (π) were the parameter most closely related to improve the biological activity of the compound 2-aminothiazole derivatives. Log EC50 = 0.7311 + 0.00965 π (r=0.6097), and Log EC50=-2.4385 + 0.0406 MR (r=0.57346). Conclusion. Small and liphopilic compounds which are very good for antiprion activity that could penetrate to the blood-brain barrier. 4-(2-(6-methylpyridin-2-yl amino)-thiazol-4-yl) benzene-1,2-diol compounds are the best antiprion activity and the lowest toxicity