Synthesis, biological evaluation and mechanism of action of benzothiazole derivatives with aromatic hydrazone moiety, a new class of antileishmanial compounds

Authors: Coimbra, E.S.; Antinarelli, L.M.R.; Lemos, A.S.O.; Da Silva Neto, A.F.; Pinheiro, A.C.; De Souza, M.V.N.
Source: Chemical Biology & Drug Design, v. 104(1). p. e14585, 2024
Publisher: Wiley

Abstract

In this work, a series of benzothiazole derivatives was synthetized and assayed against promastigotes and intracellular amastigotes of L. amazonensis, as well as the toxicity on macrophages. In addition, studies about the mechanism of action were also performed. Among the synthesized molecules, the substitution at position 4 of the aromatic ring appears to be critical for activity. The best compound exhibited IC₅₀ values of 28.86 and 7.70 μM, against promastigotes and amastigotes of L. amazonensis, respectively, being more active than miltefosine, used as reference drug. The in silico analysis of physicochemical and pharmacokinetic (ADMET) properties of this compound suggested a good profile of oral bioavailability and safety. In conclusion, the strategy of using benzothiazole nucleous in the search for new antileishmanial agents was advantageous and preliminar data provide information about the mechanism of action as well as in silico parameters suggest a good profile for preclinical studies.

Document Type: Research Article
DOI: 10.1111/cbdd.14585
Publication date:  16 de julho de 2024