Benzylidene-carbonyl compounds are active against itraconazole-susceptible and itraconazole-resistant Sporothrix brasili
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SHORT COMMUNICATION
Benzylidene-carbonyl compounds are active against itraconazole-susceptible and itraconazole-resistant Sporothrix brasiliensis Stefanie Bressan Waller 1,2 & Marlete Brum Cleff 1 & Márcia Kutscher Ripoll 2 & Mário Carlos Araújo Meireles 2 & Marina Themoteo Varela 3 & João Paulo dos S. Fernandes 3 Received: 25 March 2020 / Accepted: 3 August 2020 # Institute of Microbiology, Academy of Sciences of the Czech Republic, v.v.i. 2020
Abstract We evaluated the antifungal activity of benzylidene-carbonyl compounds (LINS03) based on the structure of gibbilimbol from Piper malacophyllum Linn. Five analogues (1–5) were synthetized following a classic aldol condensation between an aromatic aldehyde and a ketone, under basic conditions. These were tested against itraconazole-susceptible (n = 3) and itraconazole-resistant (n = 5) isolates of Sporothrix brasiliensis by M38-A2 guidelines of CLSI. All of them were fungistatic (MIC ranged of 0.11–0.22 mg/mL (1); 0.08–0.17 mg/mL (2); 0.05–0.1 mg/mL (3); 0.04–0.33 mg/mL (4); and 0.04–0.3 mg/mL (5)), highlighting compounds 2 and 3. As fungicidal, compounds 1 and 2 were highlighted (MFC ranged of 0.22–0.89 mg/mL and 0.08–1.35 mg/mL, respectively), compared with the remaining (0.77–> 3.08 mg/mL (3); 0.08–> 2.6 mg/mL (4); and 0.59–> 2.37 mg/mL (5)). The inhibitory activity was related to the benzylidene-carbonyl, whereas the phenol group and the low chain homolog seems to contribute to some extent to the fungicidal effect. Compound 2 highlighted due to the considerable fungistatic and fungicidal activities, including itraconazole-resistant Sporothrix brasiliensis. These findings support the potential usefulness of benzylidene-carbonyl compounds as promising prototypes for the development of antifungal against sporotrichosis by Sporothrix brasiliensis, including against itraconazole-resistant isolates.
Introduction Sporothrix brasiliensis is one of the most virulent agents of the sporotrichosis, a zoonotic mycosis in humans and animals, mainly in cats, which itraconazole is the first choice in the therapy (Waller et al. 2017). However, the emergence of itraconazole-resistant isolates of S. brasiliensis (Waller et al. 2017, 2018) has encouraged the search for new molecules.
* Stefanie Bressan Waller [email protected] 1
Department of Veterinary Clinics, Faculty of Veterinary, Federal University of Pelotas, Pelotas, RS 96010-900, Brazil
2
Department of Preventive Veterinary, Faculty of Veterinary, Federal University of Pelotas, Pelotas, RS 96010-900, Brazil
3
Department of Pharmaceutical Sciences, Institute of Environmental, Chemical and Pharmaceutical Sciences, Federal University of São Paulo (UNIFESP), Diadema, SP 09913-030, Brazil
Natural products are an important source for biologically active compounds, and studies with curcuminoids, phenolic acids, and flavonoids such as luteolin (Huang et al. 2016; Waller et al. 2017) stimulated us to search for novel active compounds. Both curcumin and coumaric a c i d a n a l o g u e s p o s s e s s a b e n z y
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