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

Author(s)

Silva, Daniel Gedder ; Emery, Flavio da Silva

• Document type: Journal article
• Source: Brazilian Journal of Pharmaceutical Sciences; v. 54, p. 16-pg., 2018-01-01.

Abstract

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)

• FAPESP's process: 14/50265-3 - Distribution and metabolism of natural and synthetic xenobiotics: from the comprehension of reactional process to tissue imaging generation
• Grantee: Norberto Peporine Lopes
• Support Opportunities: BIOTA-FAPESP Program - Thematic Grants
• FAPESP's process: 17/21146-4 - Heterocyclic chemistry and epigenetic for the development of library of compounds for medicinal chemistry purposes.
• Grantee: Flavio da Silva Emery
• Support Opportunities: Regular Research Grants
• FAPESP's process: 17/22001-0 - Synthesis and evaluation of new heterocyclic compounds as potential antitrypanosomal agents
• Grantee: Daniel Gedder Silva
• Support Opportunities: Scholarships in Brazil - Post-Doctoral