title: Inhibition of the dimerization and active site of HIV-1 protease by secondary metabolites from the Vietnamese mushroom Ganoderma colossum.
abstract: A new farnesyl hydroquinone, ganomycin I (1), was isolated along with ganomycin B (2) from the chloroform extract of the fruiting bodies of the Vietnamese mushroom Ganoderma colossum. These compounds inhibited HIV-1 protease with IC50 values of 7.5 and 1.0 microg/mL, respectively. Kinetic studies using Zhang-Poorman and Lineweaver plots revealed that compound 2 competitively inhibited the active site of the enzyme, whereas the tetracyclic triterpene schisanlactone A, previously isolated from the same fungus, was a dimerization inhibitor, with an IC50 value of 5.0 microg/mL. The previous findings were also confirmed by the virtual docking of both compounds with HIV-1 protease crystal structure.
authors.affiliation: Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
authors.forename: Riham Salah
authors.initials: RS
authors.lastname: El Dine
authors.forename: Ali M
authors.initials: AM
authors.lastname: El Halawany
authors.forename: Chao-Mei
authors.initials: CM
authors.lastname: Ma
authors.forename: Masao
authors.initials: M
authors.lastname: Hattori
mesh_terms: D020134:Catalytic Domain / Q000187:drug effects; D048690:Fruiting Bodies, Fungal / Q000737:chemistry; D032902:Ganoderma / Q000737:chemistry*; D016333:HIV Protease / Q000187:drug effects; D017320:HIV Protease Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects*; D006873:Hydroquinones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014744:Vietnam
chemical_list: D017320:HIV Protease Inhibitors; D006873:Hydroquinones; C408008:ganomycin B; C545411:ganomycin I; D016333:HIV Protease; C514803:p16 protease, Human immunodeficiency virus 1