Facile and divergent optimization of chromazonarol enabled the identification of simplified drimane meroterpenoids as novel pharmaceutical leads.
Eur J Med Chem
; 227: 113912, 2022 Jan 05.
Article
en En
| MEDLINE
| ID: mdl-34653771
The diversity of drimane hydroquinones was significantly expanded by the facile construction of (+)-chromazonarol relevant natural products, isomers, and analogues for the discovery of new pharmaceutical leads. The structure-activity relationship of (+)-chromazonarol relevant (non)-natural products was delineated via the synergistic interaction of the programmable synthesis and bioactivity-guided screening. The first divergent derivatization of (+)-chromazonarol demonstrated that the phenolic hydroxyl group is one inviolable requirement for antifungal effect. Pinpoint modification of (+)-yahazunol manifested the position of hydroxyl group was crucial for both antifungal and antitumor activities. (+)-Albaconol, (+)-neoalbaconol, and two (+)-yahazunol isomers (24 and 25) proved to be the novel pharmaceutical leads. The probable macromolecular targets were estimated to deliver new information about the biological potentials resident in (+)-yahazunol relevant products. This work also featured the first synthesis of (+)-albaconol and (+)-neoalbaconol, the first biological exploration of (+)-dictyvaric acid and improved preparation of (+)-8-epi-puupehedione and a promising pelorol analogue.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Ascomicetos
/
Rhizoctonia
/
Xantenos
/
Fusarium
/
Antifúngicos
Tipo de estudio:
Diagnostic_studies
Límite:
Humans
Idioma:
En
Revista:
Eur J Med Chem
Año:
2022
Tipo del documento:
Article
Pais de publicación:
Francia