Strategies towards expansion of chemical space of natural product-based compounds to enable drug discovery

Autor(es)

Silva, Daniel Gedder ; Emery, Flavio da Silva

• Tipo de documento: Artigo Científico
• Fonte: Brazilian Journal of Pharmaceutical Sciences; v. 54, p. 16-pg., 2018-01-01.

Resumo

Natural products (NPs) are an excellent source of biologically active molecules that provide many biologically biased features that enable innovative designing of synthetic compounds. NPs are characterized by high content of sp3-hybridized carbon atoms; oxygen; spiro, bridged, and linked systems; and stereogenic centers, with high structural diversity. To date, several approaches have been implemented for mapping and navigating into the chemical space of NPs to explore the different aspects of chemical space. The approaches providing novel opportunities to synthesize NP-inspired compound libraries involve NP-based fragments and ring distortion strategies. These methodologies allow access to areas of chemical space that are less explored, and consequently help to overcome the limitations in the use of NPs in drug discovery, such as lack of accessibility and synthetic intractability. In this review, we describe how NPs have recently been used as a platform for the development of diverse compounds with high structural and stereochemical complexity. In addition, we show developed strategies aiming to reengineer NPs toward the expansion of NP-based chemical space by fragment-based approaches and chemical degradation to yield novel compounds to enable drug discovery. (AU)

• Processo FAPESP: 14/50265-3 - Metabolismo e distribuição de xenobióticos naturais e sintéticos: da compreensão dos processos reacionais à geração de imagens teciduais
• Beneficiário: Norberto Peporine Lopes
• Modalidade de apoio: Auxílio à Pesquisa - Programa BIOTA - Temático
• Processo FAPESP: 17/21146-4 - Explorando a química heterocíclica e a epigenética para o desenvolvimento de compostos de interesse químico medicinal
• Beneficiário: Flavio da Silva Emery
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 17/22001-0 - Síntese e avaliação de novos compostos heterociclos como potenciais agentes tripanossomicidas
• Beneficiário: Daniel Gedder Silva
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado