title: Trypanocidal and cytotoxic evaluation of synthesized thiosemicarbazones as potential drug leads against sleeping sickness.
abstract: Thiosemicarbazones have become one of the promising compounds as new clinical candidates due to their wide spectrum of pharmaceutical activities. The wide range of their biological activities depends generally on their related aldehyde or ketone groups. Here, we report the pharmacological activities of some thiosemicarbazones synthesized in this work. Benzophenone and derivatives were used with N(4)-phenyl-3-thiosemicarbazide to synthesize corresponding five thiosemicarbazones (1-5). Their structures were characterized by spectrometrical methods analysis IR, NMR (1)H & (13)C and MS. The compounds were then screened in vitro for their antiparasitic activity and toxicity on Trypanosoma brucei brucei and Artemia salina Leach respectively. The selectivity index of each compound was also determined. Four thiosemicarbazones such as 4, 2, 3 and 1 reveal interesting trypanocidal activities with their half inhibitory concentration (IC50) equal to 2.76, 2.83, 3.86 and 8.48 μM respectively, while compound 5 (IC50 = 12.16 μM) showed a moderate anti-trypanosomal activity on parasite. In toxicity test, except compound 1, which showed a half lethal concentration LC50 >281 μM, the others exerted toxic effect on larvae with LC50 of 5.56, 13.62, 14.55 and 42.50 μM respectively for thiosemicarbazones 4, 5, 3 and 2. In agreement to their selectivity index, which is greater than 1 (SI >1), these compounds clearly displayed significant selective pharmaceutical activities on the parasite tested. The thiosemicarbazones 2-5 that displayed significant anti-trypanosomal and cytoxicity activities are suggested to have anti-neoplastic and anti-cancer activities.
authors.affiliation: Laboratoire de Chimie Organique, Physique et de Synthèse (LaCOPS), Département de Chimie, Faculté des Sciences et Techniques (FAST), Université d'Abomey-Calavi, 01 BP 4521, Cotonou, Benin.
authors.forename: Bienvenu
authors.initials: B
authors.lastname: Glinma
authors.forename: Sika D S
authors.initials: SD
authors.lastname: Kpoviessi
authors.forename: Fernand A
authors.initials: FA
authors.lastname: Gbaguidi
authors.forename: Coco N
authors.initials: CN
authors.lastname: Kapanda
authors.forename: Joanne
authors.initials: J
authors.lastname: Bero
authors.forename: Joëlle
authors.initials: J
authors.lastname: Quetin-Leclercq
authors.forename: Mansourou
authors.initials: M
authors.lastname: Moudachirou
authors.forename: Jacques
authors.initials: J
authors.lastname: Poupaert
authors.forename: Georges C
authors.initials: GC
authors.lastname: Accrombessi
authors.forename: Emma W
authors.initials: EW
authors.lastname: Gachomo
authors.forename: Lamine
authors.initials: L
authors.lastname: Baba-Moussa
authors.forename: Simeon O
authors.initials: SO
authors.lastname: Kotchoni
mesh_terms: D000818:Animals; D001156:Artemia / Q000187:drug effects*; D006801:Humans; D013882:Thiosemicarbazones / Q000138:chemical synthesis / Q000494:pharmacology*; D014346:Trypanosoma brucei brucei / Q000187:drug effects* / Q000472:pathogenicity; D014353:Trypanosomiasis, African / Q000188:drug therapy* / Q000469:parasitology / Q000473:pathology
chemical_list: D013882:Thiosemicarbazones