Malabaricone A

Arylalkanones from Horsfieldia macrobotrys are effective antidiabetic agents achieved by alpha-glucosidase inhibition and radical scavenging.[Pubmed:25920275]

Nat Prod Commun. 2015 Feb;10(2):325-8.

Horsfieldia macrobotrys Merr has long been used by Dayak people in East Kalimantan of Indonesia, for diabetes therapy. Inspired by ethnopharmacological use and promising alpha-glucosidase and radical scavenging activities, an attempt to identify the active components was carried out. Bioassay-guided isolation yielded two related arylalkanones named 1-(2,4,6-trihydroxyphenyl)-9-phenylnonan-1-one (1) and Malabaricone A (2). Arylalkanone 1 showed potent radical scavenging comparable with that of the standard antioxidant, ascorbic acid, and promising inhibition against alpha-glucosidases. Noticeably, arylalkanone 1 was 3-30 times more potent than Malabaricone A (2) in all bioassays examined, thus suggesting the critical role in exerting bioactivities of the hydroxy group on the aryl moiety. This hypothesis was also supported by reduction in inhibitory effects of the methyl ether analogues la and 2a. Arylalkanone 1 inhibited yeast alpha-glucosidase in a mixed-type manner in which the noncompetitive pathway was dominant over competitive inhibition. This study is the first report of alpha-glucosidase inhibition of arylalkenone-type compounds and the first phytochemicals from H. macrobotrys.

Comparative nuclease and anti-cancer properties of the naturally occurring malabaricones.[Pubmed:20805034]

Bioorg Med Chem. 2010 Oct 1;18(19):7043-51.

The nuclease activities of the malabaricones have been studied so as to establish a structure-activity correlation and deduce the mechanistic pathway of the process. The inactivity of Malabaricone A and malabaricone D revealed that the resorcinol moiety, present in the malabaricones did not contribute to the nuclease activity. Amongst the test compounds, malabaricone C (mal C) containing a B-ring catechol moiety showed significantly better Cu(II)-dependent nuclease activity than the partially methylated catechol derivative, mal B and curcumin. Mal C was found to bind efficiently with Cu(II) and DNA to facilitate the DNA nicking via a site-specifically generated Cu(I)-peroxo complex. Consistent with its Cu(II)-dependent nuclease property, mal C showed better cytotoxicity (IC(50)=5.26+/-1.20 muM) than curcumin (IC(50)=24.46+/-3.32 muM) against the MCF-7 human breast cancer cell line. The mal C-induced killing of the MCF-7 cells followed an apoptotic pathway involving oxidative damage to the cellular DNA.

A new acyclic diterpene acid and bioactive compounds from Knema glauca.[Pubmed:19471882]

Arch Pharm Res. 2009 May;32(5):685-92.

Investigation of the chemical constituents of the fruits of Knema glauca (Myristicaceae) yielded a new acyclic diterpene acid, named glaucaic acid 4, together with four acylphenols, including 1-(2,6-dihydroxyphenyl) tetradecan-1-one 1, Malabaricone A 6, dodecanoylphloroglucinol 7 and 1-(2,4,6-trihydroxyphenyl)-9-phenylnonan-1-one 8, two lignans sesamin 2 and asarinin 3, and a flavan, myristinin D 5. In addition, myristinin A 9 and (+/-)-7,4'-dihydroxy-3'-methoxyflavan 10 were isolated from its leaves and stems, respectively. When tested against small-cell lung cancer (NCI-H187), epidermoid carcinoma (KB) and breast cancer (BC) cell lines, compounds 1, 6-8 and 10 displayed weak to moderate cytotoxicity. The acylphenols 6-8 displayed antituberculosis activity against the microbe Mycobacterium tuberculosis with MIC values of 25, 50 and 100 microg/mL, respectively, and antiviral activity against herpes simplex virus type 1, with 7 as the most active compound (IC(50) = 3.05 microg/mL). Malabaricone A 6 was also active against the malarial parasite Plasmodium falciparum with an IC(50) value of 2.78 microg/mL.