Search

The naturally occurring bitter principle quassin (1) was converted chemically into the γ-lactone quassilactone (13) in an attempt to enhance its antiplasmodial activity. The in vitro antiplasmodial activity of 13 against Plasmodium falciparum (K1) (IC50 = 23 μM) was 40-fold greater than that of 1. However, one of the intermediates, compound 8, the 15β-hydroxy,16-O-m-chlorobenzoyl analogue of 1, was 506-fold more active than 1 against P. falciparum (IC50 = 1.8 μM) and only 3-fold less potent than chloroquine. In addition, 8 displayed the best cytotoxic/antiplasmodial ratio (112) of all of the compounds tested. In the course of this work a dimer, neoquassin ether (6), linked at C-16 was also prepared; 6 was found to have weak antiplasmodial activity (IC50 = 9.7 μM).

Four new terpenoids, comprising three nor-secofriedelanes (1−3) and one nor-friedelane (4), were isolated from Galphimia glauca, together with the known flavonol quercetin and the sterols stigmasterol and sitosterol 3-O-β-d-glucoside. The structure elucidation of the new isolates was conducted by 1D and 2D NMR techniques. Compounds 1−4 were given the trivial names galphin A, galphin B, galphin C, and galphimidin, respectively. All isolates were tested for in vitro antiprotozoal and cytotoxic activities. Quercetin was the only substance isolated that showed any antiprotozoal activity, and this was weak; the IC50 values were 14 μM against Plasmodium falciparum K1, 13.2 μM against Trypanosoma brucei brucei, and 63.8 μM against Leishmania donovani. Quercetin was found to be inactive against KB cells (IC50 = 295.8 μM).

The lupane‐type triterpene betulinic acid was isolated from an ethanol extract of the root bark of the Tanzanian tree Uapaca nitidaMüll‐Arg. (Euphorbiaceæ). The in vitroantiplasmodial IC50values of betulinic acid against chloroquine resistant (K1) and sensitive (T9‐96) Plasmodium falciparumwere found to be 19.6 µg/mL and 25.9 µg/mL, respectively. The in vitroactivities of several related triterpenes were also evaluated. Betulin was found to be inactive at 500 µg/mL for both K1 and T9‐96. Ursolic acid exhibited IC50values of 36.5 µg/mL and 28 µg/mL, and oleanolic acid exhibited IC50values of 88.8 µg/mL and 70.6 µg/mL against K1 and T9‐96, respectively. When betulinic acid was tested for in vivoactivity in a murine malaria model (P. berghei) the top dosage employed of 250 mg/kg/day was ineffective at reducing parasitaemia and exhibited some toxicity. Betulinic acid has not previously been evaluated for in vivoactivity. This is believed to be the first compound to be isolated from U. nitida. Copyright © 1999 John Wiley & Sons, Ltd.

The lupane-type triterpene betulinic acid was isolated from an ethanol extract of the root bark of the Tanzanian tree Uapaca nitida Müll-Arg. (Euphorbiaceæ). The in vitro antiplasmodial IC50 values of betulinic acid against chloroquine resistant (K1) and sensitive (T9-96) Plasmodium falciparum were found to be 19.6 µg/mL and 25.9 µg/mL, respectively. The in vitro activities of several related triterpenes were also evaluated. Betulin was found to be inactive at 500 µg/mL for both K1 and T9-96. Ursolic acid exhibited IC50 values of 36.5 µg/mL and 28 µg/mL, and oleanolic acid exhibited IC50 values of 88.8 µg/mL and 70.6 µg/mL against K1 and T9-96, respectively. When betulinic acid was tested for in vivo activity in a murine malaria model (P. berghei) the top dosage employed of 250 mg/kg/day was ineffective at reducing parasitaemia and exhibited some toxicity. Betulinic acid has not previously been evaluated for in vivo activity. This is believed to be the first compound to be isolated from U. nitida. Copyright © 1999 John Wiley & Sons, Ltd.

The Retarded Potential (RP) method, which is a boundary element technique and non-local in both space and time, is employed to discretize the fluid domain for the analysis of transient fluid–structure interaction problems. The retarded potential analysis program RPFS is coupled to the ABAQUS non-linear finite element code to form ABAQUS/RPFS. The standard RP is inherently unstable for time steps below a critical time step that is equal to the maximum distance in the fluid divided by the wave speed. A technique referred to as the Figueiredo method is used to convert the standard RP differential-delay equations for the fluid to simply delay equations, which are more stable. The Figueiredo approach extends the stability range of the standard RP by a factor of approximately 10–20, but this time step is still not small enough to be useful for analysis. Digital signal processing methods are used to further stablize the response of the fluid by removing the oscillating high-frequency noise in the time histories of the solution without introducing phase shifting or any significant damping. Stability of the coupled system is achieved by not extrapolating the structural accelerations. ABAQUS/RPFS is applied to both a rigid and elastic sphere subjected to a plane wave, and the results using the full time histories required are completely stable and quite accurate. With this procedure, the retarded potential method may yet prove to be a valuable analysis tool for transient fluid–structure interaction problems. © 1997 John Wiley & Sons, Ltd.

Intravenous injection of 6·7–60 μg of a stable prostaglandin E2analogue, 16,16-dimethyl prostaglandin E2, into 10-day-old chicks caused profound, long-lasting hypercalcaemia. Simultaneous i.v. loading with 50 μmol Ca/bird enhanced the peak response. The responses were accompanied by sedation and lowered skin temperature. Use of acute (simultaneous) 45Ca labelling indicated that the hypercalcaemic responses were due primarily to inhibition of Ca exit from extracellular fluid pools, while chronic (6-day) 45Ca labelling indicated a slower but distinct increase in mobilization of bone Ca pools.

Twenty-one alkaloids have been assessed for activities against Plasmodium falciparum (multidrug- resistant strain K1) in vitro; 18 of these are reported for the first time. Two protoberberine alkaloids, dehydrodiscretine and berberine, were found to have antiplasmodial IC50 values less than 1 μM, while seven alkaloids&sbd;allocrytopine, columbamine, dehydroocoteine, jatrorrhizine, norcorydine, thalifendine, and ushinsunine&sbd;had values between 1 and 10 μM. These results are discussed in the context of structure−activity relationships. Compounds were also assessed for antiamoebic and cytotoxic activities, but none was significantly active except for berberine, which was moderately cytotoxic.