Inhibition of the dimerization and active site of HIV-1 protease by secondary metabolites from the Vietnamese mushroom Ganoderma colossum.
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.
El Dine
Riham Salah
RS
Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
El Halawany
Ali M
AM
Ma
Chao-Mei
CM
Hattori
Masao
M
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
D017320:HIV Protease Inhibitors; D006873:Hydroquinones; C408008:ganomycin B; C545411:ganomycin I; D016333:HIV Protease; C514803:p16 protease, Human immunodeficiency virus 1