Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fungi are some of the most neglected pathogens in terms of new drug discovery. Paracoccidioidomycosis, an endemic disease to South America, is caused by dimorphic fungi of Paracoccidioides genus. Reasonable citotoxicity, limited efficacy, and frequent use of current commercial antifungals have led to the emergence of resistance. Thus, the development of new antifungals with more selectivity and large spectrum of action is mandatory. In this work, six calix[n]arenes were synthesized and their activity explored against seven isolates of P. brasiliensis and P. lutzii. p-tert-Butylcalix[4] arene (CX1) was the most potent compound against fungal cells and exhibited the lowest toxicity on healthy mammalian cells (V79, hamster lung and MDCK, dog kidney). This is the first report on the effect of calix[n] arenes as growth inhibitors of Paracoccidioides fungi.913036Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)