Tropolone and its derivatives: structure, synthesis, application in medicine (review)

Introduction. Tropolones and their derivatives are members of a family of natural products containing a tropolonoid motif, a unique cyclohepta-2,4,6-trienone fragment, which constitutes a seven-membered nonbenzenoid aromatic ring. Following the advent of organic chemistry, a substantial number of novel tropolone derivatives have been synthesized and identified. In the past decade, the number of publications employing these substances has exceeded 350. the objective of the present review was to provide a concise summary of the extant published data concerning the structural characteristics, methods of synthesis, and applications in various medical disciplines of tropolone series compounds.

Material and Methods. A comprehensive literature search was conducted using the PubMed, eLibrary, and Google Scholar databases. The search was conducted using the keywords “tropolone,” “chemical structure of tropolones,” “synthesis of tropolones,” and “biological activity of tropolones”. Of the 535 literature sources that were selected for study, 39 publications were analyzed in detail. The review includes studies from 1936 to 2024.

Results. The structural characterization of tropolones, the chemical synthesis of tropolones through diverse methodologies involving sixand seven-membered carbon rings, and the cyclization and cycloaddition reactions, are addressed. Additionally, the preparation of new compounds through the condensation of tropolone with other functional groups is discussed. A review of contemporary studies conducted on tumor cell cultures, various types of bacteria, and laboratory animals reveals that tropolone series compounds exhibit a broad spectrum of biological effects. This renders them promising lead molecules for the development of various drugs. The primary mechanism of tropolones involves the coordination of cations at the active centers of metalloenzymes. The authors of the extant works propose various pathways and targets of their action.

Conclusion. Tropolones exhibit a broad spectrum of biological activity, encompassing antiviral, antimicrobial, and antitumor properties. The study of the structure-activity relationship, coupled with the accumulation of information on the chemical and physical properties of the obtained substances, has led to the development of more effective methods of synthesis and the production of tropolone series compounds with improved efficiency and selectivity. This efficacy has been confirmed in both in vitro and in vivo studies. However, the precise mechanism(s) through which tropolones exert their biological effects remain to be elucidated. Consequently, further research in this area is imperative to elucidate the precise mechanisms of tropolones.

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