OBJECTIVES: To investigate the antileprosy potential of a set of original compounds with antimycobacterial activity.
METHODS: We developed a facile synthesis of 2-chloro-3-cyano-5-nitropyridine and synthesized a series of 3-cyano-2-dialkyldithiocarbamoyl-5-nitropyridine derivatives. In vivo therapeutic efficacy against Mycobacterium leprae was assessed in the infected mouse footpad model.
RESULTS: The compounds were active in vitro against Mycobacterium smegmatis, Mycobacterium aurum, Mycobacterium vaccae and Mycobacterium fortuitum, with MICs generally in the range of 0.4-6.25 mg/L. Reduction of the bacterial load in vivo in the mouse footpad and toxic side effects were dependent on the individual structure of the compounds and on the doses applied. Compounds 2a, 3a and 3b reduced the number of M. leprae by two orders of magnitude, comparable to the effect of dapsone. Co-administration of compounds 2a and 3a with dapsone synergistically enhanced the activity. In addition, these compounds were well tolerated over the treatment period of 7.5 months.
CONCLUSIONS: Individual synthetic dithiocarbamate derivatives have promising antileprosy activity.
BT - The Journal of antimicrobial chemotherapy C1 - http://www.ncbi.nlm.nih.gov/pubmed/16595643?dopt=Abstract DA - 2006 Jun DO - 10.1093/jac/dkl095 IS - 6 J2 - J. Antimicrob. Chemother. LA - eng N2 -OBJECTIVES: To investigate the antileprosy potential of a set of original compounds with antimycobacterial activity.
METHODS: We developed a facile synthesis of 2-chloro-3-cyano-5-nitropyridine and synthesized a series of 3-cyano-2-dialkyldithiocarbamoyl-5-nitropyridine derivatives. In vivo therapeutic efficacy against Mycobacterium leprae was assessed in the infected mouse footpad model.
RESULTS: The compounds were active in vitro against Mycobacterium smegmatis, Mycobacterium aurum, Mycobacterium vaccae and Mycobacterium fortuitum, with MICs generally in the range of 0.4-6.25 mg/L. Reduction of the bacterial load in vivo in the mouse footpad and toxic side effects were dependent on the individual structure of the compounds and on the doses applied. Compounds 2a, 3a and 3b reduced the number of M. leprae by two orders of magnitude, comparable to the effect of dapsone. Co-administration of compounds 2a and 3a with dapsone synergistically enhanced the activity. In addition, these compounds were well tolerated over the treatment period of 7.5 months.
CONCLUSIONS: Individual synthetic dithiocarbamate derivatives have promising antileprosy activity.
PY - 2006 SP - 1134 EP - 8 T2 - The Journal of antimicrobial chemotherapy TI - Synthesis and antileprosy activity of some dialkyldithiocarbamates. VL - 57 SN - 0305-7453 ER -