آنالیز کیفی و کمی برهمکنش های داروهای ضد قارچ و آلبومین توسط روش داکینگ مولکولی

Title

Qualitative and Quantitative Analysis of the Interaction of Antifungal Drugs and Albumin via Molecular Docking Method

English Abstract

Introduction Albumin is the prominent protein of plasma and drug-albumin interaction causes changes in pharmacokinetics and toxicity of drugs(1). Studying drug-albumin interaction is an important and practical research field. No systematic computational study has been dedicated to the interaction of antifungals with albumin despite their significant role in pharmaceutical medications. In the present contribution, different antifungal drugs were examined by molecular docking to find possible binding sites with albumin and obtain structural information of drug-albumin complexes. Methods Molecular docking calculations were performed by AutoDock 4.2 software(2). Interaction patterns were achieved by Ligplot. 3D structures of albumin with warfarin and diazepam as representatives of active sites 1 & 2 were extracted from Brookhaven Protein Bank (2BXD & 2BXF). Results and Discussion Results revealed that antifungals made hydrophobic contacts and H-bonds with albumin. It was found that within active site 2, Fenticonazole exhibited lowest free binding energy (-9.89 kcal.mol-1) while Flucytosin showed loosest binding to the albumin (-3.06 kcal.mol-1). In the active site 1, Oxiconazole showed tightest binding (-9.01 kcal.mol-1) while loosest contact was attributed to Fluconazole. However Fenticonazole could also achieve high score (-8.70 kcal.mol-1) within active site 1 but results indicated that polar interactions might be important in binding to active site 1 since oxiconazole possessed oxime moiety. Binding maps indicated that higher affinity of Fenticonazole might be related to possible hydrophobic contacts via additional aromatic rings attached to sulfur atom. Conclusion Current computational results revealed that different antifungal drugs are important interfering agents since they may bind to human serum albumin with relatively high binding energies (< -6 kcal.mol-1). Such studies might aid in developing novel antifungal scaffolds, comparing the mechanism and binding affinity of antifungal drugs with albumin and also obtaining structural information about drug-albumin complexes.

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