Exploring the Molecular and Structural Mechanism for Drug Induced Nephrotoxicity: A Virtual Based Approach
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Abstract
Drug-induced nephrotoxicity is increasingly recognized as a significant contributor to acute kidney injury and chronic kidney disease. Acute kidney injury is a very common diagnosis, present in up to 60% of critical patients, and its third main cause is drug toxicity. Systematic and quantitative studies of nephrotoxicity have become increasingly important due to rising concerns of drug induced nephrotoxicity. Drugs frequently interact with more than one target, with hundreds of these targets linked to the side effects of clinically used therapeutics. This is based on the hypothesize that drugs with same side effects are likely to have similar targets (Zhang et al., 2017). Developing a computational model to predict drug induced nephrotoxicity will provide a screening tool for nephrotoxicity thereby minimizing the number of nephrotoxic drugs released to the market. The study was aimed at exploring the various molecular and structural mechanisms for drug induced nephrotoxicity using computer simulation techniques; pharmacophore studies, PASSONLINE target identification and molecular docking simulation techniques. Hydrogen bond donor and hydrogen bond acceptor were the features common to nephrotoxic drugs, kidney injury molecule 1, neutrophil gelatinase associated lipocalin and type IV collagen were the common nephrotoxic targets. The nephrotoxic drugs demonstrated excellent binding affinities against the common targets and superimpose with each other and the co-crystalized ligand in the active pocket of each of the targets. These findings imply that nephrotoxic drugs potentiate the effects of these targets and might be molecular mechanism responsible for the nephrotoxicity associated with drugs.
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