Semi-Synthesis and Biological Activities of Palitantin Derivatives

• Grant number: 24/15885-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: January 01, 2025
• End date: December 31, 2025
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Roberto Gomes de Souza Berlinck
• Grantee: Vinícius Gimenes Roqueto
• Host Institution: Instituto de Química de São Carlos (IQSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil
• Associated research grant: 19/17721-9 - The role of Chemistry in holobiont adaptation, AP.TEM

Abstract

Palitantin is a secondary metabolite originally isolated from culture media of the fungus Penicillium palitans, and it is also produced by other fungal species. A fungal strain, Penicillium sp. AMF1a, from Antarctica, produces (+)-palitantin with a yield of approximately 170 mg/L, allowing for the isolation of this compound for use in larger-scale preparation of derivatives. The synthetic routes to palitantin developed to date are multi-step processes with yields not exceeding 45% and often require expensive and environmentally harmful reagents. Therefore, the production of palitantin through fermentation represents a viable alternative for obtaining gram quantities of this compound for derivative synthesis. Palitantin is structurally similar to frequentin, which was originally isolated from the fungus Penicillium frequentans. Both compounds exhibit activity against Leishmania brasiliensis and Epicoccum nigrum (palitantin), Botrytis cinerea (frequentin), and Ascochyta pisi, Fusarium solani, and Monilinia laxa (both). Additionally, palitantin has demonstrated potent inhibitory activity against the enzyme acetylcholinesterase, with an IC¿¿ value of 0.079 ¿M, which is nearly identical to that of the control substance, huperzine. Huperzine is a medication used in the treatment of Alzheimer's disease, the most common form of neurodegenerative disorder, which has shown a significant increase in the number of cases over time. Thus, this project aims to produce gram quantities of palitantin via fermentation and to prepare synthetic derivatives for the evaluation of their biological activity against various pathogens (bacteria and fungi) and in the inhibition of acetylcholinesterase.