title: Susceptibility studies of Plasmodium falciparum isolates and clones against cycloguanil and pyrimethamine using the modified in vitro microtechnique.
abstract: 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.
authors.affiliation: School of Pharmaceutical Sciences, University of Science Malaysia, Minden, Penang, Malaysia.
authors.forename: H H
authors.initials: HH
authors.lastname: Ang
authors.forename: K L
authors.initials: KL
authors.lastname: Chan
authors.forename: J W
authors.initials: JW
authors.lastname: Mak
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D002999:Clone Cells; D004351:Drug Resistance; D005493:Folic Acid Antagonists / Q000494:pharmacology*; D010963:Plasmodium falciparum / Q000187:drug effects*; D002727:Proguanil; D011739:Pyrimethamine / Q000494:pharmacology*; D014227:Triazines / Q000494:pharmacology*
chemical_list: D000962:Antimalarials; D005493:Folic Acid Antagonists; D014227:Triazines; C026009:cycloguanil; D002727:Proguanil; D011739:Pyrimethamine