Search

Invasive fungal infections are a complex challenge throughout the world because of their high incidence, mainly in critically ill patients, and high mortality rates. The antifungal agents currently available are limited; thus, there is a need for the rapid development of new drugs. In silico methods are a modern strategy to explore interactions between new compounds and specific fungal targets, but they depend on precise genetic information. Here, we discuss the main Candida spp. target genes, including information about null mutants, virulence, cytolocalization, co-regulatory genes, and compounds that are related to protein expression. These data will provide a basis for the future in silico development of antifungal drugs., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

• Pyrimido[4,5- d pyridazinone- N -acylhydrazones were synthesized by simple methodologies. • Antifungal activity of compounds was evaluated against P. brasiliensis and Candida spp. • Six compounds showed inhibition against Pb18 with MIC of 0.125 to 64 µg.mL−1. • N -acylhydrazone 5a showed potent fungicidal profile with MFC of 0.5 µg mL−1. • Compound 5a showed good synergic effect with amphotericin B and not showed toxicity. 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 , 5 m 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. [ABSTRACT FROM AUTHOR]