PMID- 34324170 OWN - NLM STAT- MEDLINE DCOM- 20211215 LR - 20231108 IS - 1678-4405 (Electronic) IS - 1517-8382 (Print) IS - 1517-8382 (Linking) VI - 52 IP - 4 DP - 2021 Dec TI - In vitro and in silico analysis reveals antifungal activity and potential targets of curcumin on Paracoccidioides spp. PG - 1897-1911 LID - 10.1007/s42770-021-00548-6 [doi] AB - The search for new compounds with activity against Paracoccidioides, etiologic agents of Paracoccidioidomycosis (PCM), is extremely necessary due to the current scenario of the available therapeutic arsenal. Treatment is restricted to three classes of antifungals with side effects. Curcumin is a polyphenol with antifungal effects that is extracted from Curcuma longa. The present work aimed to evaluate the activity of curcumin in different species of Paracoccidioides and to evaluate the potential molecular targets of curcumin using computational strategies. In addition, interactions with classic antifungals used in the treatment of PCM were evaluated. Curcumin inhibits the growth of Paracoccidioides spp. exerting a fungicidal effect. The combination of curcumin with amphotericin B, co-trimoxazole, and itraconazole showed a synergistic or additive interaction. Molecular targets as superoxide dismutase, catalase, and isocitrate lyase were proposed based on in silico approaches. Curcumin affects the fungal plasma membrane and increases the production of reactive oxygen species. Therefore, curcumin is a good alternative for the treatment of PCM. CI - (c) 2021. Sociedade Brasileira de Microbiologia. FAU - Rocha, Olivia Basso AU - Rocha OB AD - Laboratory of Molecular Biology, Institute of Biological Sciences, Federal University of Goias, Avenida Esperanca, s/n, ICB2, Sala 206, Goiania, Goias, 74690-900, Brazil. FAU - do Carmo Silva, Livia AU - do Carmo Silva L AD - Laboratory of Molecular Biology, Institute of Biological Sciences, Federal University of Goias, Avenida Esperanca, s/n, ICB2, Sala 206, Goiania, Goias, 74690-900, Brazil. FAU - de Carvalho Junior, Marcos Antonio Batista AU - de Carvalho Junior MAB AD - Laboratory of Molecular Biology, Institute of Biological Sciences, Federal University of Goias, Avenida Esperanca, s/n, ICB2, Sala 206, Goiania, Goias, 74690-900, Brazil. FAU - de Oliveira, Amanda Alves AU - de Oliveira AA AD - Laboratory of Molecular Biology, Institute of Biological Sciences, Federal University of Goias, Avenida Esperanca, s/n, ICB2, Sala 206, Goiania, Goias, 74690-900, Brazil. AD - Institute of Tropical Pathology and Public Health, Federal University of Goias, Goiania, Goias, Brazil. FAU - de Almeida Soares, Celia Maria AU - de Almeida Soares CM AD - Laboratory of Molecular Biology, Institute of Biological Sciences, Federal University of Goias, Avenida Esperanca, s/n, ICB2, Sala 206, Goiania, Goias, 74690-900, Brazil. FAU - Pereira, Maristela AU - Pereira M AUID- ORCID: 0000-0002-5482-8036 AD - Laboratory of Molecular Biology, Institute of Biological Sciences, Federal University of Goias, Avenida Esperanca, s/n, ICB2, Sala 206, Goiania, Goias, 74690-900, Brazil. maristelaufg@gmail.com. LA - eng PT - Journal Article DEP - 20210729 PL - Brazil TA - Braz J Microbiol JT - Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] JID - 101095924 RN - 0 (Antifungal Agents) RN - IT942ZTH98 (Curcumin) SB - IM MH - Antifungal Agents/pharmacology MH - Computer Simulation MH - *Curcumin/pharmacology/therapeutic use MH - Drug Synergism MH - Humans MH - In Vitro Techniques MH - *Paracoccidioides/drug effects MH - *Paracoccidioidomycosis/drug therapy/microbiology PMC - PMC8578512 OTO - NOTNLM OT - Antifungal activity OT - Curcumin OT - Paracoccidioides spp. COIS- The authors declare no competing interests. EDAT- 2021/07/30 06:00 MHDA- 2021/12/16 06:00 PMCR- 2022/07/29 CRDT- 2021/07/29 12:33 PHST- 2020/12/08 00:00 [received] PHST- 2021/06/21 00:00 [accepted] PHST- 2021/07/30 06:00 [pubmed] PHST- 2021/12/16 06:00 [medline] PHST- 2021/07/29 12:33 [entrez] PHST- 2022/07/29 00:00 [pmc-release] AID - 10.1007/s42770-021-00548-6 [pii] AID - 548 [pii] AID - 10.1007/s42770-021-00548-6 [doi] PST - ppublish SO - Braz J Microbiol. 2021 Dec;52(4):1897-1911. doi: 10.1007/s42770-021-00548-6. Epub 2021 Jul 29.