1. Evaluation of a Novel Synthetic Peptide Derived from Cytolytic Mycotoxin Candidalysin.
- Author
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Cardoso PHO, Boleti APA, Silva PSE, Mukoyama LTH, Guindo AS, Moraes LFRN, Oliveira CFR, Macedo MLR, Carvalho CME, de Castro AP, and Migliolo L
- Subjects
- Nitrates metabolism, Candida albicans, Anti-Bacterial Agents chemistry, Peptides chemistry, Pseudomonas aeruginosa, Microbial Sensitivity Tests, Escherichia coli, Mycotoxins toxicity, Mycotoxins metabolism
- Abstract
The importance of neuroinflammation in neurology is becoming increasingly apparent. In addition to neuroinflammatory diseases such as multiple sclerosis, the role of neuroinflammation has been identified in many non-inflammatory neurological disorders such as stroke, epilepsy, and cancer. The immune response within the brain involves the presence of CNS resident cells; mainly glial cells, such as microglia, the CNS resident macrophages. We evaluated the peptide Ca-MAP1 bioinspired on the C. albicans immature cytolytic toxin candidalysin to develop a less hemolytic peptide with anti-neuroinflammatory, antibacterial, and cytotoxic activity against tumor cells. In silico and in vitro studies were performed at various concentrations. Ca-MAP1 exhibits low hemolytic activity at lower concentrations and was not cytotoxic to MRC-5 and BV-2 cells. Ca-MAP1 showed activity against Acinetobacter baumannii , Escherichia coli ATCC, E. coli KPC, Klebsiella pneumoniae ATCC, Pseudomonas aeruginosa , and Staphylococcus aureus ATCC. Furthermore, Ca-MAP1 exhibits anti-neuroinflammatory activity in the BV-2 microglia model, with 93.78% inhibition of nitrate production at 18.1 µM. Ca-MAP1 presents cytotoxic activity against tumor cell line NCI-H292 at 36.3 μM, with an IC
50 of 38.4 µM. Ca-MAP1 demonstrates results that qualify it to be evaluated in the next steps to promote the control of infections and provide an alternative antitumor therapy.- Published
- 2022
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