δ-Lactam derivative from thermophilic soil fungus exhibits in vitro anti-allergic activity

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...

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Bibliographic Details
Published in:Natural product research 2012-12, Vol.26 (23), p.2168-2175
Main Authors: Andrioli, W.J., Santos, M.S., Silva, V.B., Oliveira, R.B., Chagas-Paula, D.A., Jorge, J.A., Furtado, N.A.J.C., Pupo, M.T., Silva, C.H.T.P., Naal, R.M.Z.G., Bastos, J.K.
Format: Article
Language:English
Subjects:
Animals
anti-allergic activity
Anti-Allergic Agents - chemistry
Anti-Allergic Agents - pharmacology
Ascomycota - chemistry
beta N- double prime Acetylhexosaminidase
beta-N-Acetylhexosaminidases - metabolism
Cell culture
Cell Degranulation - drug effects
Cell Line, Tumor
Cell Survival - drug effects
Computer applications
Computer Simulation
Cytotoxicity
Dose-Response Relationship, Drug
Drug development
Drug Evaluation, Preclinical - methods
Humicola grisea
Humicola grisea var thermoidea
in silico
Inhibitory Concentration 50
Ketotifen - pharmacology
Lactams - chemistry
Magnetic Resonance Spectroscopy
Molecular Structure
natural products
Phthalazines - pharmacology
Pyridones - chemistry
Pyridones - pharmacology
Rats
Soil
Soil Microbiology
thermophylic fungus
δ-lactam derivative
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Summary: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.
ISSN:1478-6419
1478-6427
DOI:10.1080/14786419.2011.647020