Aspartate‐β‐semialdeyhyde dehydrogenase as a potential therapeutic target of <i>Mycobacterium tuberculosis</i> H37Rv: Evidence from in silico elementary mode analysis of biological network model

J of Cellular Biochemistry

et al. 2018

Self Cite

Human aldose reductase (hAR) is the key enzyme in sorbitol pathway of glucose utilization and is implicated in the etiology of secondary complications of diabetes, such as, cardiovascular complications, neuropathy, nephropathy, retinopathy, and cataract genesis. It reduces glucose to sorbitol in the presence of NADPH and the major cause of diabetes complications could be the change in the osmotic pressure due to the accumulation of sorbitol. An activated form of hAR (activated hAR or ahAR) poses a potential obstacle in the development of diabetes drugs as hAR-inhibitors are ineffective against ahAR. The therapeutic efficacy of such drugs is compromised when a large fraction of the enzyme (hAR) undergoes conversion to the activated ahAR form as has been observed in the diabetic tissues. In the present study, attempts have been made to employ systems biology strategies to identify the elementary nodes of human polyol metabolic pathway, responsible for normal metabolic states, followed by the identification of natural potent inhibitors of the activated form of hAR represented by the mutant C298S for possible antidiabetic applications. Quantum Mechanical Molecular Mechanical docking strategy was used to determine the probable inhibitors of ahAR. Rosmarinic acid was found as the most potent natural ahAR inhibitor and warrants for experimental validation in the near future.

show abstract

Section: Discussionmentioning

confidence: 74%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Inhibition of C298S mutant of human aldose reductase for antidiabetic applications: Evidence from in silico elementary mode analysis of biological network model

Khan

J of Cellular Biochemistry

et al. 2018

Self Cite

show abstract

Systematic analysis to identify novel disease indications and plausible potential chemical leads of glutamate ionotropic receptorNMDAtype subunit 1,GRIN1

Ahmad

J of Molecular Recognition

2022

Self Cite

Schizophrenia is a mental illness affecting the normal lifestyle of adults and early adolescents incurring major symptoms as jumbled speech, involvement in everyday activities eventually got reduced, patients always struggle with attention and memory, reason being both the genetic and environmental factors responsible for altered brain chemistry and structure, resulting in schizophrenia and associated orphan diseases. The network biology describes the interactions among genes/proteins encoding molecular mechanisms of biological processes, development, and diseases. Besides, all the molecular networks, protein‐protein Interaction Networks have been significant in distinguishing the pathogenesis of diseases and thereby drug discovery. The present meta‐analysis prioritizes novel disease indications viz. rare and orphan diseases associated with target Glutamate Ionotropic Receptor NMDA Type Subunit 1, GRIN1 using text mining knowledge‐based tools. Furthermore, ZINC database was virtually screened, and binding conformation of selected compounds was performed and resulted in the identification of Narciclasine (ZINC04097652) and Alvespimycin (ZINC73138787) as potential inhibitors. Furthermore, docked complexes were subjected to MD simulation studies which suggests that the identified leads could be a better potential drug to recuperate schizophrenia.

show abstract

Machine Learning Toward Infectious Disease Treatment

Advances in Intelligent Systems and Computing

2018