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Susceptibility studies of Plasmodium falciparum isolates and clones against cycloguanil and pyrimethamine using the modified in vitro microtechnique. 1996

H H Ang, and K L Chan, and J W Mak
School of Pharmaceutical Sciences, University of Science Malaysia, Minden, Penang, Malaysia.

Six clones were derived from each Malaysian Plasmodium falciparum isolate and characterized for their susceptibilities against type II antifolate drugs, cycloguanil and pyrimethamine. Results showed that these isolates were of a heterogeneous population, with average IC50 values of Gombak C clones at 0.012-0.084 microM and 0.027-0.066 microM, ST 9 clones at 0.019-0.258 microM and 0.027-0.241 microM, ST 12 clones at 0.015-0.342 microM and 0.012-0.107 microM, ST 85 clones at 0.022-0.087 microM and 0.024-0.426 microM, and ST 148 clones at 0.027-0312 microM and 0.029-0.690 microM against cycloguanil and pyrimethamine, respectively. Generally, most of these clones displayed susceptibility patterns similar to their parent isolates except ST 9/A4, ST 9/A7, ST 9/B5, ST 9/D9, ST 9/D10, ST 148/A4, ST 148/A5, ST 148/A7, ST 148/F7, ST 148/F8 clones, which were sensitive at 0.027 microM, 0.019 microM, 0.022 microM, 0.063 microM, 0.037 microM, 0.031 microM, 0.042, microM, 0.042 microM, 0.062 microM, and 0.027 microM, whereas, ST 12/D7 clone was resistant at 0.342 microM, against cycloguanil respectively. However, ST 9/A4, ST 9/D8, ST 12/D5, ST 85/A5, ST 85/B3, ST 85/B4, ST 85/D3, ST 85/D7, ST 148/A6, and ST 148/A7 clones were resistant to pyrimethamine at 0.158 microM, 0.241 microM, 0.107 microM, 0.223 microM, 0.393 microM, 0.402 microM, 0.426 microM, 0.115 microM, 0.690 microM, and 0.520 microM, respectively.

UI MeSH Term Description Entries
D010963 Plasmodium falciparum A species of protozoa that is the causal agent of falciparum malaria (MALARIA, FALCIPARUM). It is most prevalent in the tropics and subtropics. Plasmodium falciparums,falciparums, Plasmodium
D011739 Pyrimethamine One of the FOLIC ACID ANTAGONISTS that is used as an antimalarial or with a sulfonamide to treat toxoplasmosis. Chloridin,Daraprim,Malocide,Tindurine
D002727 Proguanil A biguanide compound which metabolizes in the body to form cycloguanil, an anti-malaria agent. Chlorguanid,Chloroguanide,Bigumal,Chloriguane,Chloroguanide Hydrochloride,Paludrin,Paludrine,Proguanil Hydrochloride,Hydrochloride, Chloroguanide,Hydrochloride, Proguanil
D002999 Clone Cells A group of genetically identical cells all descended from a single common ancestral cell by mitosis in eukaryotes or by binary fission in prokaryotes. Clone cells also include populations of recombinant DNA molecules all carrying the same inserted sequence. (From King & Stansfield, Dictionary of Genetics, 4th ed) Clones,Cell, Clone,Cells, Clone,Clone,Clone Cell
D004351 Drug Resistance Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from DRUG TOLERANCE which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration. Resistance, Drug
D005493 Folic Acid Antagonists Inhibitors of the enzyme, dihydrofolate reductase (TETRAHYDROFOLATE DEHYDROGENASE), which converts dihydrofolate (FH2) to tetrahydrofolate (FH4). They are frequently used in cancer chemotherapy. (From AMA, Drug Evaluations Annual, 1994, p2033) Antifolate,Antifolates,Dihydrofolate Reductase Inhibitor,Folic Acid Antagonist,Dihydrofolate Reductase Inhibitors,Folic Acid Metabolism Inhibitors,Acid Antagonist, Folic,Acid Antagonists, Folic,Antagonist, Folic Acid,Antagonists, Folic Acid,Inhibitor, Dihydrofolate Reductase,Inhibitors, Dihydrofolate Reductase,Reductase Inhibitor, Dihydrofolate,Reductase Inhibitors, Dihydrofolate
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000962 Antimalarials Agents used in the treatment of malaria. They are usually classified on the basis of their action against plasmodia at different stages in their life cycle in the human. (From AMA, Drug Evaluations Annual, 1992, p1585) Anti-Malarial,Antimalarial,Antimalarial Agent,Antimalarial Drug,Anti-Malarials,Antimalarial Agents,Antimalarial Drugs,Agent, Antimalarial,Agents, Antimalarial,Anti Malarial,Anti Malarials,Drug, Antimalarial,Drugs, Antimalarial
D014227 Triazines Heterocyclic rings containing three nitrogen atoms, commonly in 1,2,4 or 1,3,5 or 2,4,6 formats. Some are used as HERBICIDES. Triazine,Benzotriazines

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