STITCH, Physicochemical, ADMET, and In Silico Analysis of Selected Mikania Constituents as Anti-Inflammatory Agents

Abstract

The Mikania genus has been known to possess numerous pharmacological activities. In the present study, we aimed to evaluate the interaction of 26 selected constituents of Mikania species with (i) cyclooxygenase 2 (COX 2), (ii) human neutrophil elastase (HNE), (iii) lipoxygenase (LOX), matrix metalloproteinase ((iv) MMP 2 and (v) MMP 9), and (vi) microsomal prostaglandin E synthase 2 (mPGES 2) inhibitors using an in silico approach. The 26 selected constituents of Mikania species, namely mikamicranolide, kaurenoic acid, stigmasterol, grandifloric acid, kaurenol, spathulenol, caryophyllene oxide, syringaldehyde, dihydrocoumarin, o-coumaric acid, taraxerol, melilotoside, patuletin, methyl-3,5-di-O-caffeoyl quinate, 3,3′,5-trihydroxy-4′,6,7-trimethoxyflavone, psoralen, curcumene, herniarin, 2,6-dimethoxy quinone, bicyclogermacrene, α-bisabolol, γ-elemene, provincialin, dehydrocostus lactone, mikanin-3-O-sulfate, and nepetin, were assessed based on the docking action with COX 2, HNE, LOX, MMP 2, MMP 9, and mPGES 2 using Discovery Studio (in the case of LOX, the Autodock method was utilized). Moreover, STITCH (Search Tool for Interacting Chemicals), physicochemical, drug-likeness, and ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) analyses were conducted utilizing the STITCH web server, the Mol-inspiration web server, and Discovery Studio, respectively. In the present study, STITCH analysis revealed only six ligands (dihydrocoumarin, patuletin, kaurenol, psoralen, curcumene, and nepetin) that showed interactions with human proteins. Physicochemical analysis showed that seventeen ligands complied well with Lipinski’s rule. ADMET analysis showed eleven ligands to possess hepatotoxic effects. Significantly, the binding free energy estimation displayed that the ligand methyl-3, 5-di-O-caffeoyl quinate revealed the highest binding energy for all the target enzymes, excluding LOX, suggesting that this may have efficacy as a non-steroidal anti-inflammatory drug (NSAID). The current study presents a better understanding of how Mikania is used as a traditional medicinal plant. Specifically, the 26 ligands of the Mikania plant are potential inhibitor against COX 2, HNE, LOX, MMP 2, MMP 9, and mPGES 2 for treatments for acute and/or chronic inflammatory diseases.

Chemical Composition and Future Perspectives of Essential Oil Obtained from a Wild Population of Stachys germanica L. Distributed in the Balkan Mountains in Bulgaria

“…However, in Bulgarian EO, its concentration is even lower, 0.23%. Caryophylene oxide belongs to the group of oxygenated sesquiterpenes and exhibits a diverse spectrum of pharmacological effects, including antibacterial, antifungal, anti-inflammatory, and antioxidant properties, it is considered as a therapeutic candidate for the prevention and treatment of cancer as well [ 49 – 51 ].…”

Molecular Docking Analysis of Selected Urtica dioica Constituents As Human Carbonic Anhydrase II (hCA-II), Human 11 Beta-Hydroxysteroid Dehydrogenases Type 1 (h11beta-HSD1), and Human Dual Specificity Phosphatase (hCDC25B) Inhibitory Agents

“…Thus, in the current investigation, we have chosen the human carbonic anhydrase II (hCA-II), human 11 beta-hydroxysteroid dehydrogenases type 1 (h11 beta-HSD1), and human dual specificity phosphatase (hCDC25B) as the target enzymes. Before carrying out the docking studies, it is important to know the toxicity nature of chosen U. dioica (Stinging nettle) ligands in order to avoid drug failure as well as to reduce drug development costs [ 13 ].…”

“…Unavailable three-dimensional structures were drawn using ChemSketch. Ligands were prepared using ChemDraw 2D and 3D [ 13 ]. Thus, these prepared three-dimensional structures were used for further study (Webina docking).…”

An In Silico Analysis of Synthetic and Natural Compounds as Inhibitors of Nitrous Oxide Reductase (N2OR) and Nitrite Reductase (NIR)

“…“The search tool for interacting chemicals” (STITCH) free-online server provides detailed information about the following; (a) metabolic pathway interactions; (b) crystal structure information; (c) binding potential; and (d) target-drug correlations [ 27 ]. In the present study, the STITCH online tool [ 28 ] was used for identifying the interactions between the twenty-two selected ligands and the proteins of the target organisms ( Paracoccus denitrificans and Hyphomicrobium denitrificans ).…”