Search

Abstract: Fourteen acridone alkaloids isolated from Lunasia amara Blanco were tested for their mechanism-based inhibition on human liver microsomal dextromethorphan O-demethylation activity, a prototype marker for cytochrome P450 2D6 (CYP2D6). Among the 14 compounds, 5-hydroxygraveroline (1), 8-methoxyifflaiamine (2), lunamarine (3), and lunine (12) increased their inhibitory activity with increasing preincubation time. Then, we further examined the possibility of mechanism-based inhibition on 5-hydroxygraveroline (1) and lunamarine (3), which showed the potent inhibition. Further investigations on 1 and 3 showed that the characteristic time- and concentration-dependent inhibition, which required a catalytic step with NADPH, was not protected by nucleophiles, and was decreased by the presence of a competitive inhibitor. Thus, 1 and 3 were concluded as mechanism-based inactivators of CYP2D6. [Copyright &y& Elsevier]

A methanol extract of the leaves of Blumea balsamifera (L.) DC. (Asteraceae) afforded a new guaian-type sesquiterpene, epiblumeaene K (1), together with four known guaian-type sesquiterpenes (2-5), three known sesquiterpenes (6-8), and nine known flavonoids (9-17) by a combination of chromatography and preparative TLC techniques. Their structures were elucidated by extensive spectroscopic methods and comparison with the literature data. Among the isolated compounds, a known sesquiterpene, beta-caryophyllene 8R,9R-oxide (6), exhibited a significant PTP1B inhibitory activity in a dose-dependent manner, with an IC50 value of 25.8 microM (5.62 microg/mL).

In order to find antiosteoporotic agents from natural resources, 32 Indonesian medicinal plants were screened for their effects on osteoblast differentiation by using alkaline phosphatase (ALP) activity in MC3T3-E1 osteoblast cells as a marker. From the extract of Barleria lupulina, which showed the most potent activity, 13 iridoid glucosides, including three new ones [8-O-acetylipolamiidic acid (1), 8-O-acetyl-6-O-(p-methoxy-cis-cinnamoyl)shanzhiside (2), and 8-O-acetyl-6-O-(p-methoxy-trans-cinnamoyl)shanzhiside (3)] were identified. Among the 13 iridoid glucosides, ipolamiide (4) showed the most potent activity in a dose-dependent manner.

Malaria is one of the most life-threatening infectious diseases worldwide and claims millions of people's lives each year. The appearance of drug-resistance Plasmodium falciparum has made the treatment of malaria increasingly problematic, and thus, it is a dire need to search the new alternatives of current drugs. In the present study, 44 cassane- and norcassane-type diterpenes isolated from Caesalpinia crista of Myanmar and Indonesia were evaluated for their antimalarial activity against the malaria parasite Plasmodium falciparum FCR-3/A2 clone in vitro. Most of the tested diterpenes displayed antimalarial activity, and norcaesalpinin E (28) showed the most potent activity with an IC50 value of 0.090 microM, more potent than the clinically used drug chloroquine (IC50, 0.29 microM). Based on the observed results, a structure-activity relationship has been established.

Ten new furanocassane-type diterpenes named, caesalpinins H-P (1-9) and norcaesalpinin F (10), were isolated from the CH(2)Cl(2) extract of the seed kernels of Caesalpinia crista, together with 13 known diterpenes. Their structures were determined based on the spectroscopic analysis. Among the isolated compounds, caesalpinin N (7) represents the first example of furanocassane-type diterpene possessing an aldehyde group at C-14.

The CH2Cl2 extract of the seed kernels of Caesalpinia crista, which exhibited promising antimalarial activity against Plasmodium berghei-infected mice in vivo, was examined and resulted in the isolation of seven new furanocassane-type diterpenes [caesalpinins C-G (1-5) and norcaesalpinins D and E (6, 7)] together with norcaesalpinins A-C (8-10) and 11 known compounds (norcaesalpinins A-C, 2-acetoxy-3-deacetoxycaesaldekarin e, caesalmin B, caesaldekarin e, caesalpin F, 14(17)-dehydrocaesalpin F, 2-acetoxycaesaldekarin e, 7-acetoxybonducellpin C, and caesalmin G). Their structures were determined on the basis of spectroscopic analysis. The isolated diterpenes showed significant dose-dependent inhibitory effects on Plasmodium falciparum FCR-3/A2 growth in vitro. Their IC50 values ranged from 90 nM to 6.5 microM, and norcaesalpinin E (7) showed the most potent inhibitory activity (IC50, 90 nM).

A methanolic extract of Orthosiphon stamineus yielded six new highly oxygenated isopimarane-type diterpenes, orthosiphols U-Z (1-6), and 15 previously reported diterpenes. The isolated diterpenes all showed significant dose-dependent inhibitory effects on the nitric oxide (NO) production in lipopolysaccharide (LPS)-activated macrophage-like J774.1 cells. Orthosiphols A (7), B (8), D (9), and X (4) showed more potent inhibitory activities than a positive control, N(G)-monomethyl-l-arginine (l-NMMA), and 1 displayed the strongest activity with an IC(50) value of 6.4 microM.

From the methanolic extract of Orthosiphon stamineus, four novel highly oxygenated isopimarane-type diterpenes named siphonols A-D (1-4) and a novel biogenetically interesting norisopimarane-type diterpene named siphonol E (5) were isolated. The new compounds 1-3 and 5 showed more potent inhibitory effects on the nitric oxide (NO) production in lipopolysaccharide (LPS)-activated macrophage-like J774.1 cells than a positive control N(G)-monomethyl-L-arginine (L-NMMA). Siphonols A-E (1-5) represent the first examples of isopimaranes oxygenated at C-20.