1. Synthesis and antifungal activity of new hybrids pyrimido[4,5-d]pyridazinone-N-acylhydrazones.
- Author
-
Rozada AMF, Rodrigues-Vendramini FAV, Gonçalves DS, Rosa FA, Basso EA, Seixas FAV, Kioshima ÉS, and Gauze GF
- Subjects
- Animals, Antifungal Agents chemical synthesis, Antifungal Agents chemistry, Chlorocebus aethiops, Dose-Response Relationship, Drug, HeLa Cells, Humans, Hydrazones chemical synthesis, Hydrazones chemistry, Microbial Sensitivity Tests, Molecular Structure, Pyridazines chemical synthesis, Pyridazines chemistry, Structure-Activity Relationship, Vero Cells, Antifungal Agents pharmacology, Candida drug effects, Hydrazones pharmacology, Paracoccidioides drug effects, Pyridazines pharmacology
- Abstract
Paracoccidioidomycosis is an endemic mycosis in Latin America for which there is a high mortality rate and limited treatment options. There are no specific drugs to treat the systemic disease. Thus, there is a need for further studies focused on the development of specific drugs. In this work we synthesized new hybrids pyrimido[4,5-d]pyridazinone-N-acylhydrazone (5a-p) by simple methodologies with good yields. The antifungal activity of compounds was evaluated against P. brasiliensis (Pb18) and Candida spp. Compounds 5a, 5f, 5i, 5 k, 5m and 5n showed significant inhibition against Pb18 with MIC of 0.125 to 64 µg mL
-1 . Compound 5a is the most promising, showing potent fungicidal profile with MFC of 0.5 µg mL-1 , synergic effect with amphotericin B, besides showing no toxicity against HeLa and Vero cells., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)- Published
- 2020
- Full Text
- View/download PDF