Abstract:
A relatively prevalent metabolic disease is diabetes mellitus (DM). The defining feature of this condition is the autoimmune system's destruction of T-cells. Thioredoxin-Interacting Protein (TXNIP) is crucially involved in degradation of ß-cells by pancreatic T-cells. This protein had been identified as a promising therapeutic target for DM management. Long-term use of traditional antidiabetic medications has been linked to numerous adverse effects. The development of new and effective medications, with little adverse effects, is a very time consuming and expensive procedure. A computer-aided drug design was used for drug designing against TXNIP. The anti-diabetic fungal metabolites were selected from the literature to be used as inhibitors of TXNIP. The druglikness of the compounds was evaluated by Using DruLiTo and DataWarior software. CheS-Mapper 2.0 was used to perform a Quantitative Structure-Activity Relationship (QSAR) investigation on 22 drug-like fungal compounds. Three compounds-Pinazaphilone A, Pinazaphilone B, and Chermesinone A had the lowest (0.01) activity cliff. Asperphenamate had the greatest apol score (81.76) whereas Albonoursin and Sterenin L had the highest bpol scores (40.66). For Pinazaphilone A and Pinazaphilone B, the fractional molecular frame (FMF) calculation yielded the lowest result (0.46). TPSA was 130.51 recoded for Pinazaphilone A and Pinazaphilone B. The log P value for all selected compounds was found 5 was seen. AutoDock Vina performed the molecular docking of fungal compounds with TXNIP. Complexes have binding energies between 9.2 and 4.6 kcal/mol. A MD simulation was performed on four docked complexes-TXNIP-Pinazaphilone A, TXNIPPinazaphilone B, TXNIP-Asperphenamate and TXNIP-Sterenin L-to determine which would make the best lead molecule. One complex only, TXNIP-Pinazaphilone B, maintained a stable conformation during the whole of the MD simulation's 80 ns run. Pinazaphilone B, Penicillium sp. secondary metabolite, was selected as lead molecule against TXNIP.
Page(s):
313-313
DOI:
DOI not available
Published:
Journal: Abstract Book on International Conference on Food and Applied Sciences (ICFAS-23) 3-5 August 23, Volume: 0, Issue: 0, Year: 2023