Article
Synthesis and trypanocidal activity of novel pyridinyl-1,3,4-thiadiazole derivatives
Registro en:
FREITAS, Rosana H. C. N. et al. Synthesis and trypanocidal activity of novel pyridinyl-1,3,4-thiadiazole derivatives. Biomedicine & Pharmacotherapy, v. 127, 110162, p. 1-14, 2020.
0753-3322
10.1016/j.biopha.2020.110162
Autor
Freitas, Rosana H. C. N.
Barbosa, Juliana M. C.
Bernardino, Patrícia
Sueth-Santiago, Vitor
Wardell, Solange M. S. V.
Wardell, James L.
Ricardo, Debora Decote
Melo, Tatiana G.
Silva, Edson F. da
Salomão, Kelly
Fraga, Carlos A. M.
Resumen
Herein, we present the design, synthesis and trypanocidal evaluation of sixteen new 1,3,4-thiadiazole derivatives from N-aminobenzyl or N-arylhydrazone series. All derivatives were assayed against the trypomastigote form of Trypanosoma cruzi, showing IC50 values ranging from 3 to 226 μM, and a better trypanocidal profile was demonstrated for the 1,3,4-thiadiazole-N-arylhydrazones (3a-g). In this series, the 2-pyridinyl fragment bound to the imine subunit of the hydrazine moiety presented pharmacophoric behavior for trypanocidal activity. Compounds 2a, 11a and 3e presented remarkable activity and excellent selectivity indexes. Compound 2a was also active against the intracellular amastigote form of T. cruzi. Moreover, its corresponding hydrochloride, compound 11a, showed the most promising profile, producing phenotypic changes similar to those caused by posaconazole, a well-known inhibitor of sterol biosynthesis. Thus, 1,3,4-thiadiazole derivative 11a could be considered a good prototype for the development of new drug candidates for Chagas disease therapy. 2022-01-01
Ítems relacionados
Mostrando ítems relacionados por Título, autor o materia.
-
Comment on "structural and vibrational studies on 1-(5-Methyl- [1,3,4] thiadiazol-2-yl)-pyrolidin-2-ol" [Spectrochimica Acta Part A, 152 (2016) 252-261]. the importance of intramolecular OH ⋯ N hydrogen bonding in the conformational properties of thiadiazol-pyrrolidin-2-ol bearing species
Laurella, Sergio Luis; Erben, Mauricio Federico (Pergamon-Elsevier Science Ltd, 2016-07)The title paper [1] reports a study on the spectroscopic and physicochemical properties of 1-(5-methyl- [1,3,4]thiadiazol-2-yl)-pyrrolidin-2-ol (MTPN) based on experimental and theoretical data. The latter ones are based ...