Prenylated Dihydrochalcones from Boronia bipinnata that Inhibit the Malarial Parasite Enzyme Target Hemoglobinase II

Abstract

High-throughput screening of a plant and marine invertebrate extract library to find natural products that inhibit the malarial parasite enzyme target hemoglobinase II led to the isolation of two new active prenylated chalcones, bipinnatones A (1) and B (2), from aerial parts of the Queensland shrub Boronia bipinnata. Their structures were assigned from interpretation of 2D NMR and high-resolution ESIMS data. Compounds 1 and 2 inhibited hemoglobinase II with IC 50 values of 64 and 52 microM, respectively.

Matching the power of high throughput screening to the chemical diversity of natural products

“…87,9 Natural products with a wide range of biological targets, including antiparasitic 175 and hormonal 176,177 activity have been reported. A focus on producing extract fractions with drug like log P characteristics has been implemented by the group.…”

Antimalarial compounds isolated from plants used in traditional medicine

“…(Tiliaceae), grewin (63), which displayed antimalarial activity against D6 and W2 (IC50 11.2 mM and 5.5 mM, respectively) without significant cytotoxicity. [41] The compound 1-O-galloyl-6-O-luteoyl-a-D-glucose (64) with an IC50 value of 2.21 mM (FCR3) was isolated from the boiled aqueous extract of the whole plant of Phyllanthus niruri L. (Euphorbiaceae). [42] Figure 4 shows coumarins with moderate or promising activity in vitro against various strains of P. falciparum.…”

“…Table 1 gives the tested phenolic derivatives presenting low or no activity in vitro against various strains of P. falciparum. [12,13,16,17,25,26,28,29,32,34,37,[40][41][42]47,48,[50][51][52][53][54][55][56][57][58][59][60][61][62][63][64][65][66] metabolites were isolated from the root extract of Bauhinia purpurea L. (Leguminosae). Among the isolated metabolites, two compounds exhibited antimalarial activity against K1, bauhinoxepin I (84) (IC50 = 10.5 mM) and bauhinoxepin J (85) (IC50 = 5.8 mM).…”

Structure Revision of Four Acylphloroglucinols Isolated from the Leaves of Syzygium polyanthum

“…Using this premise the rest of their proposed structures were constructed through the logical analysis of the remaining HMBC correlations. However 4 J CH correlations from H-3 or H-5 of an aromatic moiety to the benzylic carbonyl carbon attached at C-1 have been reported for acylphloroglucinols [8]. These correlations tend to be much weaker than the typical aromatic 3 J CH and 2 J CH correlations and so correlation intensity can be a useful tool to assign longer range couplings.…”

“…These correlations tend to be much weaker than the typical aromatic 3 J CH and 2 J CH correlations and so correlation intensity can be a useful tool to assign longer range couplings. The 2,4,6-trihydroxy substitution pattern of acylphloroglucinols results in the aromatic carbons present in these molecules having very characteristic carbon chemical shifts, with three downfield oxygenated carbons resonating at 160-165 ppm and three upfield aromatic carbons, each ortho to two oxygenated carbons, resonating at~95-110 ppm [8]. In comparison the oxygenated aromatic carbons in 1,2-dihydroxyphenyl compounds typically resonate between 145-150 ppm, while protonated aromatic carbons which are ortho to only one oxygenated carbon resonate between~110-117 ppm and quaternary aromatic carbons ortho to only one oxygenated carbon resonate between 115-120 ppm [9].…”