title: Arylthiosemicarbazones as antileishmanial agents.
abstract: Based on a screening process, we targeted substituted thiosemicarbazone as potential antileishmanial agents. Our objective was to identify the key structural elements contributing to the anti-parasite activity that might be used for development of effective drugs. A series of 32 compounds was synthesized and their efficacy was evaluated against the clinically relevant intracellular amastigotes of Leishmania donovani. From these, 22 compounds showed EC50 values below 10 μM with the most active derivative (compound 14) showing an EC50 of 0.8 μM with very low toxicity on two different mammalian cell lines. The most relevant structural elements required for higher activity indicate that the presence of a fused bicyclic aromatic ring such as a naphthalene bearing an alkyl or an alkoxy group substituent are prerequisites. Owing to the easy synthesis, high activity and low toxicity, the most active compounds could be considered as a lead for further development.
authors.affiliation: Instituto de Parasitología y Biomedicina 'López-Neyra', IPBLN-CSIC, Parque Tecnológico de Ciencias de la Salud, Avda. del Conocimiento s/n, 18016, Armilla, Granada, Spain.
authors.forename: José Ignacio
authors.initials: JI
authors.lastname: Manzano
authors.affiliation: Univ. Grenoble Alpes, Département de Pharmacochimie Moléculaire DPM UMR 5063, 38041, Grenoble, France; CNRS, DPM UMR 5063, 38041, Grenoble, France.
authors.forename: Florent
authors.initials: F
authors.lastname: Cochet
authors.affiliation: Univ. Grenoble Alpes, Département de Pharmacochimie Moléculaire DPM UMR 5063, 38041, Grenoble, France; CNRS, DPM UMR 5063, 38041, Grenoble, France.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Boucherle
authors.affiliation: Instituto de Parasitología y Biomedicina 'López-Neyra', IPBLN-CSIC, Parque Tecnológico de Ciencias de la Salud, Avda. del Conocimiento s/n, 18016, Armilla, Granada, Spain.
authors.forename: Verónica
authors.initials: V
authors.lastname: Gómez-Pérez
authors.affiliation: Univ. Grenoble Alpes, Département de Pharmacochimie Moléculaire DPM UMR 5063, 38041, Grenoble, France; CNRS, DPM UMR 5063, 38041, Grenoble, France.
authors.forename: Ahcène
authors.initials: A
authors.lastname: Boumendjel
authors.affiliation: Instituto de Parasitología y Biomedicina 'López-Neyra', IPBLN-CSIC, Parque Tecnológico de Ciencias de la Salud, Avda. del Conocimiento s/n, 18016, Armilla, Granada, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Gamarro
authors.affiliation: Univ. Grenoble Alpes, Département de Pharmacochimie Moléculaire DPM UMR 5063, 38041, Grenoble, France; CNRS, DPM UMR 5063, 38041, Grenoble, France. Electronic address: Marine.Peuchmaur@univ-grenoble-alpes.fr.
authors.forename: Marine
authors.initials: M
authors.lastname: Peuchmaur
mesh_terms: D000478:Alkylation; D000818:Animals; D000981:Antiprotozoal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D006801:Humans; D020128:Inhibitory Concentration 50; D007893:Leishmania donovani / Q000187:drug effects*; D011084:Polycyclic Aromatic Hydrocarbons; D013329:Structure-Activity Relationship; D013882:Thiosemicarbazones / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000981:Antiprotozoal Agents; D011084:Polycyclic Aromatic Hydrocarbons; D013882:Thiosemicarbazones
keywords: Arylthiosemicarbazone; Leishmania