Synthesis And Evaluation Of Ester Derivatives Of 10-Hydroxycanthin-6-one As Potential Antimicrobial Agents

The canthin-6-one alkaloids are a subclass of β-carboline alkaloids with an additional D-ring. Canthin-6-ones have been isolated from various plant sources, principally from the Rutaceae and Simaroubaceae families, and recently from fungi and marine organism. Notably, canthine-6-one alkaloids have received considerable attention owing to their high antimicrobial potencies. To exploit the potential antimicrobial activities of compounds having a canthin-6-one skeleton, a novel series of ester derivatives of 10-Hydroxycanthin-6-one were synthesized and evaluated for their bioactivity against three phytopathogenic fungi and seven bacterial strains. Furthermore, the structure-activity relationship was discussed. The results were summarized as follows:The natural compound 10-Methoxycanthin-6-one was prepared in four steps by using 5-Methoxytryptamine as a starting material. Another key parent compound, 10-Hydroxycanthin-6-one, was obtained by treating 10-Methoxycanthin-6-one with boron tribromide under an argon atmosphere. A new series of ester derivatives was obtained by the reaction of 10-Hydroxycanthin-6-one with the corresponding acyl chloride in the presence of triethylamine. The structure of each compound was characterized by 1H-NMR, 13C-NMR, and ESI-MS.The in vitro antifungal properties of all synthesized compounds were evaluated against three phytopathogenic fungi(Alternaria solani, Fusarium graminearum, and Fusarium solani) using the mycelium linear growth rate method. At a concentration of 50 μg/mL, 58% of the test items(47/81) revealed good activity, with inhibition rates of 49.9 to 100%. Compounds F4 and F7 s had the highest activity against F. graminearum, with inhibition rates of 100%, equal to that of Thiabendazole.All synthesized compounds were screened for their antibacterial activity against seven bacterial strains(Staphylococcus aureus, Escherichia coli, Pseudomonas solanacearum, Bacillus cereus, Bacillus subtilis, Ralstonia solanacearum, and Pseudomonas syringae) using the disk diffusion method. The MICs of compounds F5, F6, and F7s–F7w were determined in further studies using the micro-broth dilution method. Significant activity was observed for compounds F5, F7 s, and F7 t against all the tested bacterial strains, with MICs between 3.91 and 31.25 μg/mL. Compound F5 was active against the tested Gram-positive bacteria, with MICs equivalent to that of Penicillin Sodium.The structure-activity relationship was discussed.Structure-activity relationship for the antifungal activity, the conjugated unsaturated bonds of rings C and D are non-essential, the aliphatic ester derivatives of 10-Hydroxycanthin-6-one had much higher antifungal activity than did the aromatic ester derivatives.Structure-activity relationship for the antibacterial activity, the conjugated unsaturated bonds of rings C and D play an important role in antibacterial activity, the introduction of aromatic esters decreases the antibacterial activity.