Synthesis and Anti-Paracoccidioides Activity of Calix[n]arenes

Marcilene      Coimbra de Oliveira; Fabiano      Souza Reis; Angelo      de Fatima; Thais      Furtado Ferreira Magalhaes; Danielle      Leticia da Silva; Raphael      Rodrigues Porto; Giselle      Almeida Watanabe; Cleide      Viviane Buzanello Martins; Daniel      Leite da Silva; Ana      Lucia Tasca Gois Ruiz; Sergio      Antonio Fernandes; Joao      Ernesto de Carvalho; Maria      Aparecida de Resende-Stoianoff

Abstract

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.

Keywords: Calix[n]arenes, P-tert-Butylcalix[n]arene, Antifungal, Paracoccidioides genus, Paracoccidioidomycosis, Dimorphic fungi, Mammalian cells, phenolic, anti-Paracoccidioides, Dimorphic fungus, pathogens, P. brasiliensis, P. lutzii