title: In vitro and in vivo activity of K-130, a dihydrofolate reductase inhibitor, against Mycobacterium leprae.
abstract: The antimicrobial effects of a new dihydrofolate reductase inhibitor, K-130 (2,4-diaminodiphenyl sulfone substituted 2,4-diamino-5-benzylpyrimidine), alone and in combination with dapsone (CAS 80-08-0) against both dapsone-sensitive and dapsone-resistant strains of Mycobacterium leprae were evaluated in vitro, in cell-free culture system, and in vivo, in mouse foot pads. The minimal inhibitory concentration of K-130 against dapsone-sensitive as well as dapsone resistant strains of M, leprae was 0.03 microgram/ml, and the activity was bactericidal in both cases. However, when combined with dapsone, K-130 exhibited synergism in case of dapsone-sensitive M. leprae, while in case of dapsone-resistant M. leprae, the effect was merely additive. Similar synergistic effects were also observed in the mouse foot pad system for both types of M. leprae strains.
authors.affiliation: Florida Institute of Technology, Department of Biological Sciences, Melbourne, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Dhople
mesh_terms: D000818:Animals; D003622:Dapsone / Q000494:pharmacology; D004352:Drug Resistance, Microbial; D004357:Drug Synergism; D005260:Female; D005493:Folic Acid Antagonists / Q000494:pharmacology*; D005528:Foot / Q000473:pathology; D007917:Leprostatic Agents / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D009166:Mycobacterium leprae / Q000187:drug effects* / Q000254:growth & development; D011743:Pyrimidines / Q000494:pharmacology*; D013450:Sulfones / Q000494:pharmacology*
chemical_list: D005493:Folic Acid Antagonists; C119145:K 130; D007917:Leprostatic Agents; D011743:Pyrimidines; D013450:Sulfones; D003622:Dapsone