ABSTRACT
Eight mononuclear Pd(II) complexes containing salicylaldiminato thiosemicarbazones (saltsc-R; where R=H (1), 3-OMe (2), 3-(t)Bu (3) and 5-Cl (4)) as dinegative tridentate ligands were prepared by the reaction of the corresponding thiosemicarbazone with the precursor Pd(L)(2)Cl(2) (L=phosphatriazaadamantane or 4-picoline) in the presence of a weak base. These complexes (9-16) were characterised by a range of spectroscopic and analytical techniques including NMR spectroscopy and X-ray diffraction. These complexes along with four other Pd(II) analogues (5-8) were screened for activity in vitro against the Trichomonas vaginalis parasite. Preliminary results show that the type of ancillary ligand as well as the substituents on the aromatic ring of the salicylaldiminato thiosemicarbazone ligand influences the antiparasitic activity of these complexes.
Subject(s)
Antiprotozoal Agents/chemical synthesis , Coordination Complexes/chemical synthesis , Palladium , Thiosemicarbazones/chemical synthesis , Trichomonas vaginalis/drug effects , Antiprotozoal Agents/pharmacology , Coordination Complexes/pharmacology , Crystallography, X-Ray , Inhibitory Concentration 50 , Models, Molecular , Molecular Conformation , Thiosemicarbazones/pharmacologyABSTRACT
Trypanosoma brucei and Trichomonas vaginalis are both parasitic protozoans that are known to share many similar biochemical pathways. Aristeromycin, as well as 5'-iodovinyl and 5'-oxime analogues of adenosine, are potent inhibitors of AdoHcy hydrolase in T. brucei, an enzyme that catalyses the hydrolysis of AdoHcy to adenosine and L-homocysteine. To help determine the role of this enzyme in T. vaginalis, we have tested a library of 5'-modified adenosine derivatives, including 5'-deoxy-5'-(iodomethylene)-adenosine and related 6-N-cyclopropyl analogues. Our results indicate that these inhibitors are effective at inhibiting the growth of T. vaginalis, by as much as 95%.
Subject(s)
Adenosine/analogs & derivatives , Adenosylhomocysteinase/antagonists & inhibitors , Antiprotozoal Agents/chemistry , Cyclopropanes/chemistry , Trichomonas vaginalis/enzymology , Adenosine/chemical synthesis , Adenosine/chemistry , Adenosine/pharmacology , Adenosylhomocysteinase/metabolism , Amino Acid Sequence , Antiprotozoal Agents/chemical synthesis , Antiprotozoal Agents/pharmacology , Molecular Sequence Data , Sequence Alignment , Structure-Activity RelationshipABSTRACT
Trichomonas vaginalis, a human-infectious protozoan, can display resistance to treatment by metronidazole. A library of 3,4-dichloroaniline amides based on propanil, an herbicide, has been synthesized and screened to test susceptibility to these analogs. From this preliminary study, the most effective compound 15, inhibits growth of the organism by 66% and 69% on the two strains tested, T1 and G3, respectively.
