Evaluation of the inhibitory potentials of selected compounds from Costus spicatus (Jacq.) rhizome towards enzymes associated with insulin resistance in polycystic ovarian syndrome: an in silico study

Abstract

Background Polycystic ovary syndrome (PCOS) is a chronic endocrine disorder prevalent in premenopausal women and is characterized by a range of physiological and biochemical abnormalities which may include reproductive, endocrine, and metabolic alterations such as insulin resistance. Insulin resistance is the hallmark of PCOS as it predisposes the affected subjects to a higher risk of impaired glucose tolerance and type 2 diabetes mellitus (T2DM). In this study, the inhibitory activities of phytosterols and saccharides from aqueous extract of Costus spicatus rhizome were investigated against phosphoenolpyruvate carboxykinase (PEPCK), α-amylase, β-glucosidase, and fructose 1,6-biphosphatase (FBPase) in silico as potential novel therapeutic targets for T2DM-associated-PCOS. Phytochemical constituents of the plant were determined using gas chromatography-mass spectrophotometry (GC-MS), while molecular docking of the compounds with PEPCK, α-amylase, β-glucosidase, and FBPase was conducted using Vina. Thereafter, the binding modes were determined using Discovery Studio Visualizer, 2020. Results GCMS analysis of an aqueous extract of Costus spicatus rhizome revealed the presence of three compounds with a higher binding affinity for all enzymes studied compared to metformin. The compounds also interacted with key amino acid residues crucial to the enzyme’s activities. This study identified Lyxo-d-manno-nononic-1,4-lactone as potential multi-target inhibitors of PEPCK, α-amylase, β-glucosidase, and FBPase with reasonable pharmacokinetic properties and no significant toxicity. Conclusion These compounds can be explored as potential therapeutic agents for the management of insulin resistance in PCOS, subject to further experimental validation.

Computational Discovery of Novel Imidazole Derivatives as Inhibitors of SARS-CoV-2 Main Protease: An Integrated Approach Combining Molecular Dynamics and Binding Affinity Analysis

“…Experimental findings can validate or disprove the predicted toxicities, providing valuable insights into the actual risk associated with the compounds. Additionally, there is potential to repurpose these compounds as antibacterial and anticancer agents, exploring their effectiveness in these applications [54][55][56][57][58]. Thus, it is recommended to conduct experimental studies to further investigate these compounds and explore their potential for development as novel drugs for the treatment of SARS-CoV-2.…”

Evaluation of the anti‐PCOS Potential of Ethanolic Extract of Ocimum Gratissimum (Linn.) Leaf in Letrozole‐Induced Polycystic Ovarian Syndrome in Wistar Rats

“…for female fertility and menstruation. [16][17][18] Natural products like pheoniflorin, catechins, licorice, and isosorbol have been shown in numerous scientific investigations to be promising as an alternate treatment for PCOS. [19][20][21][22][23][24][25][26] Treatment of syndromes with signs and symptoms linked to one another and with a disease is one area of medical practice where doctors frequently encounter difficulty.…”

In silico Evaluation of the Inhibitory Potential of Cymbopogonol from Cymbopogon citratus Towards Falcipain-2 (FP2) Cysteine Protease of Plasmodium falciparum

“…14 The advent of bio-computational tools has replaced the employment of traditional methods in the development and discovery of drugs. 15 This is because using the bioinformatics technique is viable for designing and producing new medications of biomedical interest and takes less time and effort. 1 Also, compared to the traditional method, an advantage of the bio-computational approach is its ability to predict the binding affinity, ligand-protein interaction, and ADMET properties of the ligand of interest.…”