In silico studies of bioactive compounds from selected African plants with inhibitory activity against nitric oxide synthase and arginase implicated in asthma

Abstract

Background It is a known fact that arginine is a common substrate for arginase and nitric oxide synthase (NOS). However, an imbalance between both enzymes could lead to a change in airway responses. Reports suggest that increased activities of both enzymes could lead to airway hyper-responsiveness. Thus, the requests for NOS inhibitors that can also inhibit arginase as the elevated activities of both enzymes have detrimental consequence on airways in asthma. Bioactive compounds from Azadirachta indica, Crinum glaucum, and Mangifera indica are documented for anti-inflammatory, immunomodulatory, anti-histaminic, smooth-muscle relaxants, and anti-allergic potentials. However, the mechanisms of action of these bioactive compounds in conferring the aforementioned protections are not well characterized. The objective of this present study is to assess in silico inhibitory potentials of these bioactive compounds against NOS and arginase via binding at their active sites. The crystal structures of NOS and arginase were retrieved from the protein database, while the bioactive compounds were retrieved from PubChem. Drug-likeness of the selected bioactive compounds was assessed using DruLiTo software. The successful compounds were docked with active sites of enzymes using AutoDock Vina docking software, and the docked complexes were analyzed using LigPlot and protein-ligand profiler web server. Results The findings of the study revealed that the bioactive compounds from A. indica, C. glaucum, and M. indica were able to interact with the active sites of NOS and arginase with the exception of gallic acid (from M. indica) and nimbandiol (from A. indica); these compounds showed differential binding energies (kcal/mol) and a number of them had higher binding energies than l-arginine when docked with NOS. Conclusion Conclusively, the in silico analysis proposes that these compounds could prove to be probable anti-asthmatic drugs.

Anti-inflammatory Principles of the Plant Family Amaryllidaceae

“…Crinamine and lycorine reflected binding energies (-9.2 and -8.5 kcal/mol, respectively) that were better than that of the NOS substrate L-arginine (-5.9 kcal/mol), but slightly lower than that seen for the NOS inhibitor cromolyn sodium (-10.7 kcal/mol) [125]. Both compounds penetrated deeply into the substrate metabolism site of NOS and established hydrogen bond interactions with Gly355 and Trp356, which could be rationalized in terms of their similar chemical scaffolds [125]. Crinamine (12) interacted hydrophobically with Phe353, while its aromatic ring was involved in π-stacking with Trp178 [125].…”

“…Both compounds penetrated deeply into the substrate metabolism site of NOS and established hydrogen bond interactions with Gly355 and Trp356, which could be rationalized in terms of their similar chemical scaffolds [125]. Crinamine (12) interacted hydrophobically with Phe353, while its aromatic ring was involved in π-stacking with Trp178 [125]. There were hydrophobic interactions for lycorine with Val185, Val418 and Ala423 [125].…”

“…Crinamine (12) interacted hydrophobically with Phe353, while its aromatic ring was involved in π-stacking with Trp178 [125]. There were hydrophobic interactions for lycorine with Val185, Val418 and Ala423 [125].…”

“…The other members of the library exhibited IC 50 s that were in excess of 200 M N-cis-feruloyltyramine 129) were described from the bulb EtOH extract of Zephyranthes candida [116]. Examined for inhibitory effects on NO production in LPS-stimulated (1 g/mL) RAW264.7 macrophages, five compounds (2,11,109,125,127) exhibited good activities (IC 50 s 4.6-21.3 M) relative to dexamethasone (IC 50 0.6 M), with the remaining twenty having IC 50 s that were >200 M [116]. Interestingly, the three most active compounds (haemanthidine 2, haemanthamine 11, 11-hydroxyvittatine 125) were all closely related structures belonging to the crinane alkaloid group of the Amaryllidaceae [116].…”

“…Lycorine (1) (IC 50 2.5 M) and crinamine (12) (IC 50 1.8 M) as referenced above were shown to be better inhibitors of NO production in LPS-activated mouse peritoneal macrophages than guanidinoethyl disulphide (IC 50 7.4 M) [113]. Consequently, docking studies were carried out with both compounds to establish their binding capacities at the NOS active site [125].…”