Hyptolactones and Their Biological Potential: A Systematic Review

Area of Science:

• Natural Product Chemistry
• Pharmacology
• Medicinal Chemistry

Background:

• Hyptolactones are a class of compounds structurally related to pironetin, a natural product with known antitumor effects.
• These lactones possess potential antitumor properties, warranting investigation into their biological activities.

Purpose of the Study:

• To systematically review the cytotoxic and other biological effects of natural hyptolactones.
• To identify the structural features responsible for the observed biological activities.

Main Methods:

• A systematic review was conducted following PRISMA guidelines, searching databases like PubMed Central, ScienceDirect, Scopus, and Web of Science.
• 272 records were evaluated, leading to the inclusion of 61 articles detailing 72 plant-derived and 14 fungal-derived hyptolactones.
• The SYRCLE tool was used for risk of bias assessment in animal studies.

Main Results:

• 58 of the identified hyptolactones exhibited biological activity, primarily cytotoxic, antibacterial, and antifungal effects.
• Cytotoxicity was specifically observed in α,β-unsaturated δ-lactones, suggesting this functional group is key to their activity.
• The α,β-unsaturated lactone moiety is also present in pironetin, reinforcing its role in biological effects.

Conclusions:

• Hyptolactones, particularly α,β-unsaturated δ-lactones, demonstrate significant potential for therapeutic applications due to their cytotoxic and antimicrobial properties.
• There is a notable lack of data regarding the in vivo biological effects of hyptolactones.
• Further in-depth biological studies, including in vivo models, are essential to fully elucidate and expand the therapeutic potential of hyptolactones.