In:
Evidence-Based Complementary and Alternative Medicine, Hindawi Limited, Vol. 2022 ( 2022-6-8), p. 1-15
Abstract:
Diabetes mellitus (DM) is a very common metabolic disorder/disease. The deterioration of β-cells by autoimmune system is the hallmark of this disease. Thioredoxin-Interacting Protein (TXNIP) is responsible for β-cells degradation by T-cells in the pancreas. This protein had been declared a good drug target for controlling DM. Lots of side effects have been reported as a result of long-time consumption of conventional antidiabetic drugs. The development of new and effective drugs with the minimal side effects needs time. TXNIP was selected as a target for Computer-Aided Drug Design. The antidiabetic fungal metabolite compounds were selected from the literature. The compounds were screened for their drug-likeness properties by DruLiTo and DataWarior tools. Twenty-two drug-like fungal compounds were subjected to Quantitative Structure-Activity Relationship (QSAR) analysis by using CheS-Mapper 2.0. The lowest (0.01) activity cliff was found for three compounds: Pinazaphilone A, Pinazaphilone B, and Chermesinone A. The highest value for apol (81.76) was shown by Asperphenamate, while Albonoursin and Sterenin L showed highest score (40.66) for bpol. The lowest value (0.46) for fractional molecular frame (FMF) was calculated for Pinazaphilone A and Pinazaphilone B. TPSA for Pinazaphilone A and Pinazaphilone B was 130.51 Å2. log P 〈 5 was observed for all the twenty-two compounds. Molecular docking of fungal compounds with TXNIP was done by AutoDock Vina. The binding energy for complexes ranged between −9.2 and −4.6 kcal/mol. Four complexes, TXNIP-Pinazaphilone A, TXNIP-Pinazaphilone B, TXNIP-Asperphenamate, and TXNIP-Sterenin L, were selected for MD simulation to find out the best lead molecule. Only one complex, TXNIP-Pinazaphilone B, showed a stable conformation throughout the 80 ns run of MD simulation. Pinazaphilone B derived from the Penicillium species fungi was selected as the lead molecule for development of antidiabetic drug having the least side effects.
Type of Medium:
Online Resource
ISSN:
1741-4288
,
1741-427X
DOI:
10.1155/2022/7040547
Language:
English
Publisher:
Hindawi Limited
Publication Date:
2022
detail.hit.zdb_id:
2148302-4
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