Chemically engineered extracts as an alternative source of bioactive natural product-like compounds.
The access to libraries of molecules with interesting biomolecular properties is a limiting step in the drug discovery process. By virtue of a long molecular evolution process, natural products are recognized as biologically validated starting points in structural space for library development. We introduce here a strategy to generate natural product-like libraries. A semisynthetic mixture of compounds was produced by diversification of a natural product extract through the chemical transformation of common chemical functionalities in natural products into chemical functionalities rarely found in nature. The resulting mixture showed antifungal activity against Candida albicans, whereas the starting extract did not show such activity. Bioguided fractionation led to the isolation of a previously undescribed active semisynthetic pyrazole. The result illustrates how biological activity can be generated by designed chemical diversification of a natural product mixture, and represents the proof of principle of an alternative strategy for producing natural product-like libraries from natural products libraries.
López
Silvia N
SN
Farmacognosia, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario. Suipacha 531, S2002LRK Rosario, Argentina.
Ramallo
I Ayelen
IA
Sierra
Manuel Gonzalez
MG
Zacchino
Susana A
SA
Furlan
Ricardo L E
RL
D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001688:Biological Products / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects; D002616:Chemical Engineering; D002851:Chromatography, High Pressure Liquid; D015195:Drug Design; D006834:Hydrazines; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests
D000935:Antifungal Agents; D001688:Biological Products; D006834:Hydrazines; D007202:Indicators and Reagents; C029424:hydrazine