ps-15 and Malaria--Falciparum

ps-15 has been researched along with Malaria--Falciparum* in 4 studies

Other Studies

4 other study(ies) available for ps-15 and Malaria--Falciparum

ArticleYear
The antimalarial triazine WR99210 and the prodrug PS-15: folate reversal of in vitro activity against Plasmodium falciparum and a non-antifolate mode of action of the prodrug.
    The American journal of tropical medicine and hygiene, 1999, Volume: 60, Issue:6

    We have studied the reversal of activity against Plasmodium falciparum of WR99210, a triazine antimalarial drug, and of the pro-drug PS-15 by folic acid (FA) and folinic acid (FNA). Folic acid and FNA inhibit the growth of P. falciparum in vitro at concentrations > 10(-4.5) and 10(-3.5) mol/L, respectively. The activity of pyrimethamine against Kenyan strains M24 and K39 is reduced 10-12-fold by 10(-5) mol/L of FA, and virtually eliminated by 10(-5) mol/L of FNA. Folates do not antagonise the action of WR99210 against Kenyan strains, and only partially antagonize the action of WR99210 action against the Southeast Asian strains V1/S and W282. Similarly, FA and FNA exerted weak or no antagonism of the action of PS-15. The inability of folates to antagonize the action of WR99210 can be explained in terms of high drug-enzyme affinity, but this does not account for the inability of FA and FNA to antagonize PS-15. These results suggest that action of PS-15 against P. falciparum is primarily due to a non-folate mechanism.

    Topics: Animals; Antidotes; Antimalarials; Asia, Southeastern; Dose-Response Relationship, Drug; Drug Resistance; Folic Acid; Folic Acid Antagonists; Hematinics; Humans; Inhibitory Concentration 50; Kenya; Leucovorin; Malaria, Falciparum; Plasmodium falciparum; Prodrugs; Proguanil; Triazines

1999
Direct comparison of antimalarial activity among PS-15 combination therapies by bioassay of serum samples from treated Saimiri sciureus.
    The Journal of parasitology, 1997, Volume: 83, Issue:3

    Sixteen Saimiri sciureus monkeys were administered PS-15-atovaquone, PS-15-sulfamethoxazole, PS-15-dapsone, PS-15 alone, and atovaquone alone. The in vitro antimalarial activity of serum against Plasmodium falciparum obtained from these monkeys at 3, 6, and 12 hr after the administration of drug(s) were measured by bioassay and analyzed by Duncan's and Newman-Keul's tests. PS-15-atovaquone was found to be the most effective antimalarial combination, followed by PS-15-sulfamethoxazole, PS-15-dapsone, PS-15 alone, and atovaquone alone. These dual PS-15 combinations are effective combinations and, in-particular, PS-15-atovaquone is worthy of further evaluation.

    Topics: Animals; Antimalarials; Atovaquone; Biological Assay; Dapsone; Disease Models, Animal; Drug Synergism; Drug Therapy, Combination; Humans; Malaria, Falciparum; Naphthoquinones; Proguanil; Regression Analysis; Saimiri; Sulfamethoxazole

1997
The activity of PS-15 in combination with sulfamethoxazole.
    Tropical medicine and parasitology : official organ of Deutsche Tropenmedizinische Gesellschaft and of Deutsche Gesellschaft fur Technische Zusammenarbeit (GTZ), 1994, Volume: 45, Issue:2

    PS-15 is a novel biguanide folate antagonist that is metabolized in vivo to WR99210, a metabolite that is extremely active in vitro against multi-drug resistant strains of Plasmodium falciparum. When PS-15 was administered in combination with sulfamethoxazole to healthy Saimiri sciureus monkeys, the serum antimalarial activity was considerably greater than that observed in monkeys that received PS-15 alone. Further studies should be carried out to determine the value of PS-15/sulfonamide combinations in the treatment of human malaria infections and in preventing the emergence of drug-resistant parasites.

    Topics: Animals; Antimalarials; Biological Assay; Drug Combinations; Drug Resistance, Multiple; Drug Synergism; Folic Acid Antagonists; Malaria, Falciparum; Plasmodium falciparum; Proguanil; Saimiri; Sulfamethoxazole

1994
PS-15: a potent, orally active antimalarial from a new class of folic acid antagonists.
    The American journal of tropical medicine and hygiene, 1993, Volume: 49, Issue:1

    A new, orally-active inhibitor of dihydrofolic acid reductase (DHFR), PS-15 (N-(3-(2,4,5-trichlorophenoxy)propyloxy)-N'-(1-methylethyl)- imidocarbonimidic diamide hydrochloride), has significant activity against drug-resistant Plasmodium falciparum. It is not cross-resistant with other inhibitors of DHFR (e.g., pyrimethamine and cycloguanil). Although it bears similarities to proguanil, PS-15 represents a new antifolate class of drugs that we have named oxyguanils or hydroxylamine-derived biguanides. This compound displays intrinsic antimalarial activity and also is metabolized in vivo to WR99210, an extremely active triazine inhibitor of DHFR. When tested in vitro against drug-resistant clones of P. falciparum, PS-15 was more active than proguanil, and the putative metabolite, WR99210, was more active than the proguanil metabolite cycloguanil. The drug is also more active as well as less toxic than proguanil when administered orally to mice infected with P. berghei. When administered orally to Aotus monkeys infected with multidrug-resistant P. falciparum, PS-15 was more active than either proguanil or WR99210. In 1973, WR99210 underwent clinical trials for safety and tolerance in volunteers. The trials showed gastrointestinal intolerance and limited bioavailability; further development of the drug was abandoned. Because PS-15 has intrinsic antimalarial activity, is not cross-resistant with other DHFR inhibitors, and can be metabolized to WR99210 in vivo, oral administration of this new drug should circumvent the shortcomings and retain the advantages found with both proguanil and WR99210.

    Topics: Administration, Oral; Animals; Antimalarials; Aotus trivirgatus; Atovaquone; Drug Synergism; Folic Acid Antagonists; Imides; Injections, Subcutaneous; Malaria, Falciparum; Mice; Naphthoquinones; Phenyl Ethers; Plasmodium falciparum; Proguanil; Sulfamethoxazole; Triazines

1993