Novel hybrid selenosulfonamides as potent antileishmanial agents

• Published in: European journal of medicinal chemistry Vol. 74; pp. 116 - 123
• Main Authors: Baquedano, Ylenia, Moreno, Esther, Espuelas, Socorro, Nguewa, Paul, Font, María, Gutierrez, Kilian Jesús, Jiménez-Ruiz, Antonio, Palop, Juan Antonio, Sanmartín, Carmen
• Format: Journal Article
• Language: English
• Published: ISSY-LES-MOULINEAUX Elsevier Masson SAS 03.03.2014; Elsevier
• Subjects: Antiprotozoal Agents - pharmacology; Chemistry, Medicinal; Diselenides; Leishmania donovani - drug effects; Leishmania infantum - drug effects; Leishmanicidal agents; Life Sciences & Biomedicine; Magnetic Resonance Spectroscopy; Mass Spectrometry; Pharmacology & Pharmacy; Science & Technology; Selenium - chemistry; Selenocompounds; Sulfonamides; Sulfonamides - pharmacology; Diselenides; Selenocompounds; Sulfonamides; Leishmanicidal agents; CUTANEOUS-LEISHMANIASIS; DIAGNOSIS; ANALOGS; DEATH; INHIBITORS; VISCERAL LEISHMANIASIS; DERIVATIVES; DISCOVERY
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2013.12.030

Diselenide and sulfonamide derivatives have recently attracted considerable interest as leishmanicidal agents in drug discovery. In this study, a novel series of sixteen hybrid selenosulfonamides has been synthesized and screened for their in vitro activity against Leishmania infantum intracellular amastigotes and THP-1 cells. These assays revealed that most of the compounds exhibited antileishmanial activity in the low micromolar range and led us to identify three lead compounds (derivatives 2, 7 and 14) with IC50 values ranging from 0.83 to 1.47 μM and selectivity indexes (SI) over 17, much higher than those observed for the reference drugs miltefosine and edelfosine. When evaluated against intracellular amastigotes, hybrid compound 7 emerged as the most active compound (IC50 = 2.8 μM), showing higher activity and much less toxicity against THP-1 cells than edelfosine. These compounds could potentially serve as templates for future drug-optimization and drug-development efforts for their use as therapeutic agents in developing countries. [Display omitted] •Selenosulfonamides exhibited a notable inhibition of Leishmania infantum amastigotes growth.•Some compounds combined a very good antileishmanial activity with low toxicity.•The sulfonamide group plus diselenide moiety result in hybrid antileishmanial agents.•The molecular symmetry is a useful template to design new active leishmanicidal agents.