Hydrazones as Potential Antimelanoma Prototypes: A Systematic and Patent Review

Introduction: Hydrazones are chemical compounds with the potential to inhibit various neoplasms, including melanoma, a highly metastatic and multidrug-resistant cancer. This study aimed to systematically review the literature and analyze patents to assess the potential of hydrazones as prototype anti-melanoma agents. Methods: Following PRISMA guidelines (OSF registration: DOI 10.17605/OSF.IO/3AWR9), a systematic search was conducted in PubMed/Medline, Web of Science, ScienceDirect, and Scopus for studies published from January 2019 to February 2024 using the terms "hydrazone" and "melanoma". Only original Englishlanguage studies with experimental evaluation of anti-melanoma activity, in vitro and/or in vivo, were included. Patent searches were also carried out in ESPACENET, WIPO, LENS, and Google Patents using the IPC code A61P35/00. Results: From 1,072 records, 35 articles met eligibility criteria. All studies reported in vitro anti-melanoma activity of hydrazones; however, none included in vivo assays. N-acylhydrazones were the most frequently investigated subclass, featured in 19 studies. The patent analysis identified 41 filings using the combined terms "hydrazone AND melanoma", with Google Patents accounting for the majority (29 filings). Discussion: Hydrazones, particularly N-acylhydrazones, showed significant in vitro activity and selectivity, surpassing traditional drugs like cisplatin in some cases. The limited number of patent filings might indicate difficulties with protecting intellectual property, including effects from the COVID-19 pandemic. However, methodological differences and the lack of in vivo data are still major challenges. This emphasizes the need for more consistent and applicable research. Conclusion: Despite their potential, further studies are needed to validate hydrazones as a distinct class of antineoplastic agents.