Bhat A.R., Athar F., Van Zyl R.L., Chen C.-T., Azam A.
Synthesis and biological evaluation of novel 4-substituted 1-{[4-(10,15,20-triphenylporphyrin-5-yl)phenyl]methylidene} thiosemicarbazides as new class of potential antiprotozoal agents
Department of Chemistry, Jamia Millia Islamia, Jamia Nagar, New Delhi-110025, India; Center for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi-110025, India; Pharmacology Division, Department of Pharmacy and Pharmacology, University of the Witwatersrand, Johannesburg 2193, South Africa
Bhat, A.R., Department of Chemistry, Jamia Millia Islamia, Jamia Nagar, New Delhi-110025, India; Athar, F., Department of Chemistry, Jamia Millia Islamia, Jamia Nagar, New Delhi-110025, India, Center for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi-110025, India; Van Zyl, R.L., Pharmacology Division, Department of Pharmacy and Pharmacology, University of the Witwatersrand, Johannesburg 2193, South Africa; Chen, C.-T., Pharmacology Division, Department of Pharmacy and Pharmacology, University of the Witwatersrand, Johannesburg 2193, South Africa; Azam, A., Department of Chemistry, Jamia Millia Islamia, Jamia Nagar, New Delhi-110025, India
A novel series of 4-substituted 1-{[4-(10,15,20-triphenylporphyrin-5-yl) phenyl]methylidene}thiosemicarbazide, 4a -4n, was synthesized in 9-21% yield by the condensation of 4-(10,15,20-triphenylporphyrin-5-yl)benzaldehyde (3) with various substituted thiosemicarbazides in presence of catalytic amount of AcOH. These compounds were assayed for in vitro antiamoebic activity, and the results showed that out of 14 compounds 9 were found with IC50 values lower than metronidazole corresponding to 1.05- to 4.7-fold increase in activity. MTT Assay showed that all the compounds are nontoxic to human kidney epithelial cell line. 4-(m-Toluidinyl)-1-{[4- (10,15,20-triphenylporphyrin-5-yl)phenyl]methylidene} thiosemicarbazide (4h) showed the highest antiamoebic activity with least cytotoxicity. Some of the compounds were screened for their antimalarial activities and ability to inhibit β-haematin formation, but none of them showed an activity better than chloroquine and quinine. Only one compound out of six showed an activity comparable to standard drug. © 2008 Verlag Helvetica Chimica Acta AG, Zürich.
1,2,3,4 tetrahydro n' [[4 (10,15,20 triphenylporphyrin 5 yl)phenyl]methylidene]quinoline 1 carbothiohydrazide; 3 (4,5 dimethyl 2 thiazolyl) 2,5 diphenyltetrazolium bromide; 4 (10,15,20 triphenylporphyrin 5 yl)benzaldehyde; 4 (2 chlorobenzyl) 1 [[4 (10,15,20 triphenylporphyrin 5 yl)phenyl]methylidene]thiosemicarbazide; 4 (2 methylphenyl) 1 [[4 (10,15,20 triphenylporphyrin 5 yl)phenyl]methylidene]thiosemicarbazide; 4 (3 methylphenyl) 1 [[4 (10,15,20 triphenylporphyrin 5 yl)phenyl]methylidene]thiosemicarbazide; 4 (4 methylphenyl) 1 [[4 (10,15,20 triphenylporphyrin 5 yl)phenyl]methylidene]thiosemicarbazide; 4 benzyl 4 phenyl 1 [[4 (10,15,20 triphenylporphyrin 5 yl)phenyl]methylidene]thiosemicarbazide; 4 cyclohexyl 1 [[4 (10,15,20 triphenylporphyrin 5 yl)phenyl]methylidene]thiosemicarbazide; 4 cyclohexyl 4 methyl 1 [[4 (10,15,20 triphenylporphyrin 5 yl)phenyl]methylidene]thiosemicarbazide; 4 cyclooctyl 1 [[4 (10,15,20 triphenylporphyrin 5 yl)phenyl]methylidene]thiosemicarbazide; 4 cyclopentyl 1 [[4 (10,15,20 triphenylporphyrin 5 yl)phenyl]methylidene]thiosemicarbazide; 4 methyl 4 phenyl 1 [[4 (10,15,20 triphenylporphyrin 5 yl)phenyl]methylidene]thiosemicarbazide; 4 methyl n' [[4 (10,15,20 triphenylporphyrin 5 yl)phenyl]methylidene]piperizine 1 carbothiohydrazide; 4 phenyl n' [[4 (10,15,20 triphenylporphyrin 5 yl)phenyl]methylidene]piperazine 1 carbothiohydrazide; 5 [4 (1,3 dioxolan 2 yl)phenyl] 10,15,20 triphenylporphyrin; antiprotozoal agent; chloroquine; hematin; metronidazole; n' [[4 (10,15,20 triphenylporphyrin 5 yl)phenyl]methylidene]pyrrolidine 1 carbothiohydrazide; quinine; thiosemicarbazide derivative; unclassified drug; antiprotozoal agent; porphyrin; semicarbazide derivative; thiosemicarbazide; antimalarial activity; article; controlled study; cytotoxicity; drug screening; drug synthesis; Entamoeba histolytica; epithelium cell; human; human cell; IC 50; in vitro study; inhibition kinetics; kidney epithelium; protein synthesis; Amoeba; animal; chemical structure; chemistry; classification; drug effect; Plasmodium; structure activity relation; synthesis; Amoeba; Animals; Antiprotozoal Agents; Molecular Structure; Plasmodium; Porphyrins; Semicarbazides; Structure-Activity Relationship