Inferring Therapeutic Targets in Candida albicans and Possible Inhibition through Natural Products: A Binding and Physiological Based Pharmacokinetics Snapshot

Despite being responsible for invasive infections, fungal pathogens have been underrepresented in computer aided therapeutic target mining and drug design. Excess of causes candidiasis, causative of thrush and vaginal infection due to off-balance. In this study, we attempted to mine drug targets ( =...

Full description

Saved in:
Bibliographic Details
Published in:Life (Basel, Switzerland) Switzerland), 2022-10, Vol.12 (11), p.1743
Main Authors: Basharat, Zarrin, Khan, Kanwal, Jalal, Khurshid, Alnasser, Sulaiman Mohammed, Majeed, Sania, Zehra, Marium
Format: Article
Language:English
Subjects:
Absorption
ADMET
Aldolase
Bioavailability
CADD
Candida albicans
Candidiasis
Chelerythrine
Cirrhosis
Drug development
dynamics simulation
Fructose-bisphosphate aldolase
Fungal infections
Genes
Genomes
Hepatotoxicity
Hydrazine
Hydrazines
Infections
Libraries
Liver cirrhosis
Medicine
Natural products
Permeability
Pharmacokinetics
Pharmacology
Physiology
Proteins
Proteomics
Renal function
Simulation
Therapeutic applications
Therapeutic targets
Toxicity
Tropical diseases
Yeasts
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Despite being responsible for invasive infections, fungal pathogens have been underrepresented in computer aided therapeutic target mining and drug design. Excess of causes candidiasis, causative of thrush and vaginal infection due to off-balance. In this study, we attempted to mine drug targets ( = 46) using a subtractive proteomic approach in this pathogenic yeast and screen natural products with inhibition potential against fructose-bisphosphate aldolase (FBA) of the The top compound selected on the basis of best docking score from traditional Indian medicine/Ayurvedic library was (4-Hydroxybenzyl)thiocarbamic acid, from the ZINC FBA inhibitor library was ZINC13507461 (IUPAC name: [(2R)-2-hydroxy-3-phosphonooxypropyl] (9E,12E)-octadeca-9,12-dienoate), and from traditional Tibetan medicine/Sowa rigpa was Chelerythrine (IUPAC name: 1,2-Dimethoxy-12-methyl-9H-[1,3]benzodioxolo[5,6-c]phenanthridin-12-ium), compared to the control (2E)-1-(4-nitrophenyl)-2-[(4-nitrophenyl)methylidene]hydrazine. No Ames toxicity was predicted for prioritized compounds while control depicted this toxicity. (4-Hydroxybenzyl)thiocarbamic acid showed hepatotoxicity, while Chelerythrine depicted hERG inhibition, which can lead to QT syndrome, so we recommend ZINC13507461 for further testing in lab. Pharmacological based pharmacokinetic modeling revealed that it has low bioavailability and hence, absorption in healthy state. In cirrhosis and renal impairment, absorption and plasma accumulation increased so we recommend further investigation into this occurrence and recommend high dosage in further tests to increase bioavailability.
ISSN:2075-1729
2075-1729
DOI:10.3390/life12111743