title: HIV-1 integrase and neuraminidase inhibitors from Alpinia zerumbet.
abstract: AIDS and influenza are viral pandemics and remain one of the leading causes of human deaths worldwide. The increasing resistance of these diseases to synthetic drugs demands the search for novel compounds from plant-based sources. In this regard, the leaves and rhizomes of Alpinia zerumbet, a traditionally important economic plant in Okinawa, were investigated for activity against HIV-1 integrase (IN) and neuraminidase (NA). The aqueous extracts of leaves and rhizomes had IN inhibitory activity with IC(50) values of 30 and 188 μg/mL, whereas against NA they showed 50% inhibition at concentrations of 43 and 57 μg/mL, respectively. 5,6-Dehydrokawain (DK), dihydro-5,6-dehydrokawain (DDK), and 8(17),12-labdadiene-15,16-dial (labdadiene) were isolated from the rhizomes and were tested for enzyme inhibitions. DK and DDK strongly inhibited IN with IC(50) of 4.4 and 3.6 μg/mL, respectively. Against NA, DK, DDK, and labdadiene exhibited mixed type of inhibition with respective IC(50) values of 25.5, 24.6, and 36.6 μM and K(i) values ranging from 0.3 to 2.8 μM. It was found that DDK is a slow and time-dependent reversible inhibitor of NA, probably with a methoxy group as its functionally active site. These results suggest that alpinia could be used as a source of bioactive compounds against IN and NA and that DK and DDK may have possibilities in the design of drugs against these viral diseases.
authors.affiliation: Department of Biochemistry and Applied Bioscience, The United Graduate School of Agricultural Sciences, Kagoshima University, Kagoshima 890-0065, Japan.
authors.forename: Atul
authors.initials: A
authors.lastname: Upadhyay
authors.forename: Jamnian
authors.initials: J
authors.lastname: Chompoo
authors.forename: Wataru
authors.initials: W
authors.lastname: Kishimoto
authors.forename: Tadahirio
authors.initials: T
authors.lastname: Makise
authors.forename: Shinkichi
authors.initials: S
authors.lastname: Tawata
mesh_terms: D032429:Alpinia / Q000737:chemistry*; D000998:Antiviral Agents; D004224:Diterpenes / Q000302:isolation & purification / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D019427:HIV Integrase; D009439:Neuraminidase / Q000037:antagonists & inhibitors*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry; D011753:Pyrones / Q000302:isolation & purification / Q000494:pharmacology; D027343:Rhizome / Q000737:chemistry
chemical_list: D000998:Antiviral Agents; D004224:Diterpenes; D004791:Enzyme Inhibitors; D010936:Plant Extracts; D011753:Pyrones; C553742:labdadienedial; C052297:5,6-dehydrokawain; D019427:HIV Integrase; D009439:Neuraminidase; C514801:p31 integrase protein, Human immunodeficiency virus 1