Tropolonoids: Unveiling Natural Multi-Target Compounds with Therapeutic Potential

Tropolonoids (tropone-containing compounds) – including natural products like tropolone, hinokitiol (β-thujaplicin), colchicine, puberulic acid, and β-thujaplicinol, as well as synthetic analogs such as bistropolones – exhibit a broad spectrum of pharmacological activities. They demonstrate significant antibacterial, antifungal, antiviral, and antitumor properties, in part by inhibiting metalloenzymes and other molecular targets. For example, tropolone and hinokitiol potently inhibit zinc-dependent metalloproteases and exhibit broad antimicrobial efficacy. Dihydroxytropolones, such as β-thujaplicinol, selectively inhibit the ribonuclease H activity of HIV-1 and hepatitis B virus. Tropolonoids have demonstrated anticancer relevance through diverse mechanisms. Colchicine, a tropolone-bearing alkaloid, binds to tubulin and disrupts microtubule polymerization, thereby arresting cell division. Hinokitiol, on the other hand, induces DNA demethylation by downregulating DNA methyltransferase 1 (DNMT1) in cancer cells. These examples underscore the pharmacological significance of tropolonoids as versatile lead compounds in drug discovery, with promising applications spanning antimicrobials to anticancer agents.