IN SILICO SCREENING OF SOME OLD DRUGS FOR NEW APPROACHES IN HEART FAILURE

Abstract

FAILURE (Abstract): Aim : The aim of the present study is to discover new approaches for old drugs, targeting heart failure (HF), using in silico studies. Material and methods : Several old drugs, belong different chemical and therapeutical classes: oral hypoglycemic drugs (sulfonylurea), proton pump inhibitors, nonsteroidal anti-inflammatory drugs, statins, H 1 /H 2 antagonists, antineoplastic drugs, alfa-adrenergic agonists, vitamins and antioxidants, were tested for affinity to glycogen synthase kinase 3 beta (GSK-3β), using in silico molecular docking studies. In-dirubin-3’-monoxime (I3M) and adenylyl-imidodiphosphate (AMP-PNP), were used as GSK-3β reference inhibitors. Moreover, the drugs with the best docking score for GSK-3β, were included in an ADME-Tox study to predict their pharmacokinetic profile. Results: The used computational method was validated using RSMD variation (less than 2 Å) recorded for GSK-3β inhibitors (I3M and AMP-PNP). The results showed that the binding of drugs to GSK-3β involve direct hydrogen bonds and van der Waals interactions with key amino acids from active site, Lys85, Asp133, Val135, Glu137, Arg141, Gln185, Asp200 and Arg220. Conclusions : Based on in silico results, in term of affinity for GSK-3β and ADME Tox profile, several drugs have theoretical premises to have beneficial effects in HF and could be propose for repurposing approach, which look of finding new clinical indications for existing drugs