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

Authors

  • A. SAVA “Grigore T. Popa” University of Medicine and Pharmacy Iasi
  • Bianca Stefania PROFIRE “Grigore T. Popa” University of Medicine and Pharmacy Iasi
  • Florentina LUPASCU “Grigore T. Popa” University of Medicine and Pharmacy Iasi
  • Lenuta PROFIRE “Grigore T. Popa” University of Medicine and Pharmacy Iasi

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, H1/H2 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. Indirubin-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.

Author Biographies

  • A. SAVA, “Grigore T. Popa” University of Medicine and Pharmacy Iasi

    Faculty of Pharmacy,
    Department of Pharmaceutical Sciences (I)
    Division of Analytical Chemistry

  • Bianca Stefania PROFIRE, “Grigore T. Popa” University of Medicine and Pharmacy Iasi

    Faculty of Medicine
    Department of Medical Specialties (I). Division of Internal Medicine

  • Florentina LUPASCU, “Grigore T. Popa” University of Medicine and Pharmacy Iasi

    Faculty of Pharmacy
    Department of Pharmaceutical Sciences (I)
    Division of Pharmaceutical and Therapeutic Chemistry

  • Lenuta PROFIRE, “Grigore T. Popa” University of Medicine and Pharmacy Iasi

    Faculty of Pharmacy
    Department of Pharmaceutical Sciences (I)
    Division of Pharmaceutical and Therapeutic Chemistry

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Additional Files

Published

2023-09-30

Issue

Vol. 127 No. 3 (2023): The Medical-Surgical Journal

Section

PHARMACY

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