Hyptolactones and Their Biological Potential: A Systematic Review

Six-heptyl-5,6-dihydro-2H-pyran-2-ones and their analogues, named in this work as hyptolactones, are substances that have great antitumor potential because they are structurally related to pironetin, an important natural product with well-established antitumor effects. To investigate the cytotoxic potential and other biological effects of natural hyptolactones, a systematic review was performed according to the PRISMA guidelines. The search was conducted on databases: PubMed Central, ScienceDirect, Scopus and Web of Science. The authors independently evaluated 272 records after insertion into the Rayyan platform, including 61 articles (Cohen's Kappa: 0.94), which indicated the existence of 72 hyptolactones originating from plants and 14 from fungi. Of these, 58 demonstrated some type of biological activity, the main ones being cytotoxic, antibacterial and antifungal effects. The SYRCLE tool was used to assess the risk of bias in animal studies. As only the α,β-unsaturated δ-lactones were cytotoxic, it is assumed that the biological effects of the hyptolactones are due to the α,β-unsaturated lactone group, also present in pironetin. Despite promising results, there is a lack of data regarding the biological effects of these lactones, especially in vivo models. Thus, scientific evidence of their therapeutic potential motivates more in-depth biological studies, enabling greater expansion of their potential.