title: 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.
abstract: 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 IC(50) 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 beta-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.
authors.affiliation: Department of Chemistry, Jamia Millia Islamia, Jamia Nagar, New Delhi-110025, India.
authors.forename: Abdul R
authors.initials: AR
authors.lastname: Bhat
authors.forename: Fareeda
authors.initials: F
authors.lastname: Athar
authors.forename: Robyn L
authors.initials: RL
authors.lastname: Van Zyl
authors.forename: Chien-Teng
authors.initials: CT
authors.lastname: Chen
authors.forename: Amir
authors.initials: A
authors.lastname: Azam
mesh_terms: D000656:Amoeba / Q000187:drug effects; D000818:Animals; D000981:Antiprotozoal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000145:classification / Q000494:pharmacology*; D015394:Molecular Structure; D010961:Plasmodium / Q000187:drug effects; D011166:Porphyrins / Q000737:chemistry*; D012663:Semicarbazides / Q000138:chemical synthesis* / Q000145:classification / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000981:Antiprotozoal Agents; D011166:Porphyrins; D012663:Semicarbazides; C005151:thiosemicarbazide