title: Inhibition of inflammatory mediators and reactive oxygen and nitrogen species by some depsidones and diaryl ether derivatives isolated from Corynespora cassiicola, an endophytic fungus of Gongronema latifolium leaves.
abstract: In this study, some depsidones and diaryl ether derivatives isolated from Corynespora cassicola, a fungi endophyte of Gongronema latifolium, were assessed for their anti-inflammatory potentials. The isolated metabolites corynesidone A (1), corynesidone C (2), corynesidone D (3) and corynether A (4) were screened for their effects on tumour necrosis factor-α (TNF-α), inducible nitric oxide (iNO), and reactive oxygen species (ROS) and reactive nitrogen species (RNS) production by stimulated RAW264.7 macrophages. Concentration of 1, 2, 3 and 4 up to 100 μM did not remarkably affect the viability of treated macrophages. The compounds were found to cause a concentration-dependent decrease in lipopolysaccharide-induced TNF-α and iNO in RAW264.7 cells. Pre-treatment with 100 μM of 1, 2, 3 and 4 suppressed iNO by as much as 96.28%, 95.71%, 78.14% and 73.28%; with IC(50) of 8.16, 9.49, 15.29 and 26.52 μM, respectively. Similarly, pre-treatment with 100 μM of 1, 2, 3 and 4 caused an inhibition of 99.17%, 99.59%, 95.02% and 74.07% in the formation of iNO production, respectively, with IC(50) of 1.88, 3.99, 7.48 and 37.22 μM. Treatment of with compounds 1-4 (10, 30 and 100 µM) followed by stimulation with phorbol 12-myristate 13-acetate (1 µM) caused significant (p < 0.05) suppression of ROS/RNS-evoked chemiluminescence of luminol by as much as 100.96 ± 1.88%, 98.59 ± 1.38%, 87.35 ± 1.41% and 79.22 ± 0.30%, respectively at 100 µM. The depsidone derivatives (1-4) showed more potent inhibition of TNF-α and NO production and better scavenging ROS/RNS than the diaryl ether derivative (4). These chemical scaffolds can serve as suitable lead molecules for further development into novel anti-inflammatory and/or anti-cancer agents.
authors.affiliation: Department of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Nnamdi Azikiwe University , Awka, Anambra State , Nigeria .
authors.forename: Festus Basden C
authors.initials: FB
authors.lastname: Okoye
authors.forename: Chukwuemeka S
authors.initials: CS
authors.lastname: Nworu
authors.forename: Peter A
authors.initials: PA
authors.lastname: Akah
authors.forename: Charles O
authors.initials: CO
authors.lastname: Esimone
authors.forename: Abdessamad
authors.initials: A
authors.lastname: Debbab
authors.forename: Peter
authors.initials: P
authors.lastname: Proksch
mesh_terms: D000818:Animals; D029062:Apocynaceae / Q000737:chemistry / Q000382:microbiology; D001203:Ascomycota / Q000737:chemistry*; D002460:Cell Line; D053630:Depsides / Q000737:chemistry / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000737:chemistry / Q000494:pharmacology*; D007783:Lactones / Q000737:chemistry / Q000494:pharmacology*; D008264:Macrophages; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018515:Plant Leaves / Q000737:chemistry / Q000382:microbiology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D053630:Depsides; D016166:Free Radical Scavengers; D007783:Lactones; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; C000875:depsidone; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse