Synthesis and Biological Activities of C1-Substituted Acylhydrazone <i>β</i>-Carboline Analogues as Antifungal Candidates

Abstract

In our ongoing work to create potential antifungal agents, we synthesized and tested a group of C1-substituted acylhydrazone β-carboline analogues 9a–o and 10a–o for their effectiveness against Valsa mali, Fusarium solani, Fusarium oxysporum, and Fusarium graminearum. Their compositions were analyzed using different spectral techniques, such as 1H/13C NMR and HRMS, with the structure of 9l being additionally confirmed through X-ray diffraction. The antifungal evaluation showed that, among all the target β-carboline analogues, compounds 9n and 9o exhibited more promising and broad-spectrum antifungal activity than the commercial pesticide hymexazol. Several intriguing findings regarding structure–activity relationships (SARs) were examined. In addition, the cytotoxicity test showed that these acylhydrazone β-carboline analogues with C1 substitutions exhibit a preference for fungi, with minimal harm to healthy cells (LO2). The reported findings provide insights into the development of β-carboline analogues as new potential antifungal agents.

Keywords

• <i>β</i>-carboline
• acylhydrazone
• antifungal activity
• structure–activity relationship
• cytotoxicity