Improved production of palitantin by design of experiments and semi-synthesis of palitantin derivatives for bioactivity assessment

Author(s):Show less -

Santucci, Pedro M. ; de Oliveira, Caroline R. ; Monteiro, Afif F. ; Mendes, Giovana R. ; de Amorim, Marcelo R. ; Rosa, Gabriel H. S. ; Sette, Lara D. ; Marchi, Rafael C. ; Deflon, Victor M. ; dos Santos, Pedro H. T. ; Carvalho, Gabriela G. ; Brocchi, Marcelo ; Guido, Rafael V. C. ; Ferreira, Antonio G. ; de Oliveira, Kleber T. ; Berlinck, Roberto G. S.

• Document type: Journal article
• Source: Fitoterapia; v. 180, p. 10-pg., 2024-12-05.

Abstract

A new method for the production and isolation of (+)-palitantin (1) is herein reported, from cultures of the fungal strain Penicillium sp. AMF1a. (+)-Palitantin was isolated in 160 mg/L yield, as an alternative procedure to obtain 1 at a larger scale. The complete spectroscopic characterization, including conformational analysis, is presented for (+)-palitantin (1) and for its derivatives 3-alpha-palitantol (2), 3-beta-palitantol (3), (Z)-palinitrorin (4), (Z)-paliphenin (5), (Z)-palifluorin (6) and (E)-palifluorin (7). The absolute configuration of the palitantin portion was confirmed by X-ray analysis of compound 4. The (4-(trifluoromethyl)benzyl)-hydrazone derivatives (6 and 7) displayed moderate biological activities. (Z)-Palifluorin (6) exhibited moderate antiplasmodial activity, while (E)-palifluorin (7) displayed weak antibacterial activity against E. faecalis and S. aureus, while palitantin itself was inactive in the same bioassays, indicating that the semi-synthesis of nitrogenated derivatives of 1 may be of potential interest to generate bioactive palitantin derivatives. (AU)

• FAPESP's process: 20/01229-5 - Bioactive metabolites of bacterial flora microorganisms from non-filtering marine animals
• Grantee: Marcelo Rodrigues de Amorim
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 23/04020-8 - APIs synthesis using enabling technologies: approaches involving electrosynthesis and photocatalysis under continuous flow conditions
• Grantee: Kleber Thiago de Oliveira
• Support Opportunities: Regular Research Grants
• FAPESP's process: 22/01063-5 - Characterization of the antiplasmodial activity of natural products isolated from fungal metabolites as lead candidates for Malaria
• Grantee: Giovana Rossi Mendes
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 19/17721-9 - The role of Chemistry in holobiont adaptation
• Grantee: Roberto Gomes de Souza Berlinck
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 23/07721-7 - Screening of a library of synthetic and natural compounds for antibacterial activity to ESKAPE group bacterial strains
• Grantee: Pedro Henrique Torquato dos Santos
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 15/01017-0 - Multi-use instrument approved and awarded in the project 2013/50228-8, name of instrument: ultra-performance liquid chromatograph coupled with a high resolution mass spectrometer
• Grantee: Roberto Gomes de Souza Berlinck
• Support Opportunities: Multi-user Equipment Program