Synthesis and antifungal activity of new hybrids pyrimido[4,5-d]pyridazinone-N-acylhydrazones.

• 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]