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Open AccessArticle

Evaluation of Novel Chalcone-Thiosemicarbazones Derivatives as Potential Anti-Leishmania amazonensis Agents and Its HSA Binding Studies

1
Instituto de Química, Departamento de Química Orgânica, Universidade Federal Rural do Rio de Janeiro, Seropédica 23.890-000, Rio de Janeiro, Brazil
2
Programa de Pós-graduação em Ciência, Tecnologia e Inovação em Agropecuária, Universidade Federal Rural do Rio de Janeiro, Seropédica, Seropédica 23890-000, Rio de Janeiro, Brazil
3
Instituto SENAI de Inovação em Química Verde, Maracanã 20271-030, Rio de Janeiro, Brazil
4
Laboratório de Bioquímica de Tripanosomatídeos, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro 21040-900, Brazil
*
Authors to whom correspondence should be addressed.
Biomolecules 2019, 9(11), 643; https://doi.org/10.3390/biom9110643
Received: 22 September 2019 / Revised: 20 October 2019 / Accepted: 21 October 2019 / Published: 23 October 2019
(This article belongs to the Section Chemical Biology)
A series of seven chalcone-thiosemicarbazones (5a5g) were synthesized and evaluated as potential new drugs (anti-leishmanial effect). Although four of the chalcone-thiosemicarbazones are already known, none of them or any compound in this class has been previously investigated for their effects on parasites of the Leishmania genus. The compounds were prepared in satisfactory yields (40–75%) and these compounds were evaluated against promastigotes, axenic amastigotes and intracellular amastigotes of L. amazonensis after 48 h of culture. The half maximal inhibitory concentration (IC50) values of the intracellular amastigotes were determined to be in the range of 3.40 to 5.95 µM for all compounds assayed. The selectivity index showed value of 15.05 for 5a, whereas pentamidine (reference drug) was more toxic in our model (SI = 2.32). Furthermore, to understand the preliminary relationship between the anti-leishmanial activity of the chalcone-thiosemicarbazones, their electronic (σ), steric (MR) and lipophilicity (π) properties were correlated, and the results indicated that moieties with electronic withdrawing effects increase the anti-leishmanial activity. The preliminary pharmacokinetic evaluation of one of the most active compound (5e) was studied via interaction to human serum albumin (HSA) using multiple spectroscopic techniques combined with molecular docking. The results of antiparasitic effects against L. amazonensis revealed the chalcone-thiosemicarbazone class to be novel prototypes for drug development against leishmaniasis. View Full-Text
Keywords: Leishmania amazonensis; promastigotes; intracellular amastigotes; chalcone-thiosemicarbazones; human serum albumin; spectroscopy; molecular docking Leishmania amazonensis; promastigotes; intracellular amastigotes; chalcone-thiosemicarbazones; human serum albumin; spectroscopy; molecular docking
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MDPI and ACS Style

Mendes, E.P.; Goulart, C.M.; Chaves, O.A.; Faiões, V.S.; Canto-Carvalho, M.M.; Machado, G.C.; Torres-Santos, E.C.; Echevarria, A. Evaluation of Novel Chalcone-Thiosemicarbazones Derivatives as Potential Anti-Leishmania amazonensis Agents and Its HSA Binding Studies. Biomolecules 2019, 9, 643.

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