title: Δ-lactam derivative from thermophilic soil fungus exhibits in vitro anti-allergic activity.
abstract: From cultures of thermophilic soil fungus Humicola grisea var thermoidea, a δ-lactam derivative (3-(2-(4-hydroxyphenyl)-2-oxoethyl)-5,6-dihydropyridin-2(1H)-one) that displayed anti-allergic activity was isolated, which was predicted by in silico computational chemistry approaches. The in vitro anti-allergic activity was investigated by β-hexosaminidase release assay in rat basophilic leukaemia RBL-2H3 cells. The δ-lactam derivative exhibited similar anti-allergic activity (IC(50) = 18.7 ± 6.7 µM) in comparison with ketotifen fumarate (IC(50) = 15.0 ± 1.3 µM) and stronger anti-allergic activity than azelastine (IC(50) = 32.0 µM). Also, the MTT cytotoxicity assay with RBL-2H3 cells showed that δ-lactam does not display cytotoxicity at concentrations lower than 50 µM. This study suggests that the δ-lactam derivative has the potential to be used as a lead compound in the development of anti-allergic drugs for clinical use in humans.
authors.affiliation: Departamento de Ciências Farmacêuticas, Universidade de São Paulo, Avenida do Café, s/n, CEP 14040-903, Ribeirão Preto, São Paulo, Brasil.
authors.forename: W J
authors.initials: WJ
authors.lastname: Andrioli
authors.forename: M S
authors.initials: MS
authors.lastname: Santos
authors.forename: V B
authors.initials: VB
authors.lastname: Silva
authors.forename: R B
authors.initials: RB
authors.lastname: Oliveira
authors.forename: D A
authors.initials: DA
authors.lastname: Chagas-Paula
authors.forename: J A
authors.initials: JA
authors.lastname: Jorge
authors.forename: N A J C
authors.initials: NA
authors.lastname: Furtado
authors.forename: M T
authors.initials: MT
authors.lastname: Pupo
authors.forename: C H T P
authors.initials: CH
authors.lastname: Silva
authors.forename: R M Z G
authors.initials: RM
authors.lastname: Naal
authors.forename: J K
authors.initials: JK
authors.lastname: Bastos
mesh_terms: D000818:Animals; D018926:Anti-Allergic Agents / Q000737:chemistry* / Q000494:pharmacology*; D001203:Ascomycota / Q000737:chemistry*; D015550:Cell Degranulation / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D020128:Inhibitory Concentration 50; D007665:Ketotifen / Q000494:pharmacology; D007769:Lactams / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010793:Phthalazines / Q000494:pharmacology; D011728:Pyridones / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D012988:Soil Microbiology; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism
chemical_list: C580602:3-(2-(4-hydroxyphenyl)-2-oxoethyl)-5,6-dihydropyridin-2(1H)-one; D018926:Anti-Allergic Agents; D007769:Lactams; D010793:Phthalazines; D011728:Pyridones; D001619:beta-N-Acetylhexosaminidases; D007665:Ketotifen; C020976:azelastine