Efficacy of scopadulcic acid A against Plasmodium falciparum in vitro.
Scoparia dulcis is a perennial herb widely distributed in many tropical countries. It is used as an herbal remedy for gastrointestinal and many other ailments, and in Nicaragua extracts are used to treat malaria. Phytochemical screening has shown that scopadulcic acid A (SDA), scopadulcic acid B (SDB), and semisynthetic analogues are pharmacologically active compounds from S. dulcis. SDB has antiviral activity against Herpes simplex virus type 1, antitumor activity in various human cell lines, and direct inhibitory activity against porcine gastric H(+), K(+)-ATPase. A methyl ester of scopadulcic acid B showed the most potent inhibitory activity against gastric proton pumps of 30 compounds tested in one study. Compounds with antiviral, antifungal, and antitumor activity often show activity against Plasmodium falciparum. In P. falciparum, the plasma membrane and food vacuole have H(+)-ATPases and the acidocalcisome has an H(+)-Ppase. These proton pumps are potential targets for antimalarial therapy and may have their function disrupted by compounds known to inhibit gastric proton pumps. We tested pure SDA and found in vitro activity against P. falciparum with an IC(50) of 27 and 19 microM against the D6 and W2 clones, respectively. The IC(50) against the multidrug-resistant isolate, TM91C235, was 23 microM.
Riel
Michael A
MA
Department of Parasitology, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Silver Spring, Maryland 20910-7500, USA. Michael.riel@na.amedd.army.mil
Kyle
Dennis E
DE
Milhous
Wilbur K
WK
D000818:Animals; D000962:Antimalarials / Q000097:blood / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D002738:Chloroquine / Q000494:pharmacology; D004224:Diterpenes / Q000097:blood / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D004351:Drug Resistance; D006801:Humans; D066298:In Vitro Techniques; D020128:Inhibitory Concentration 50; D015767:Mefloquine / Q000494:pharmacology; D010946:Plants, Medicinal / Q000737:chemistry*; D010963:Plasmodium falciparum; D028083:Scrophulariaceae / Q000737:chemistry*
D000962:Antimalarials; D004224:Diterpenes; C457250:scopadulcic acid A; C058658:scopadulcic acid B; D002738:Chloroquine; D015767:Mefloquine