Synthesis and Antimicrobial Activity of Novel 4-Hydroxy-2-quinolone Analogs.

Alkyl quinolone has been proven to be a privileged scaffold in the antimicrobial drug discovery pipeline. In this study, a series of new 4-hydroxy-2-quinolinone analogs containing a long alkyl side chain at C-3 and a broad range of substituents on the C-6 and C-7 positions were synthesized. The antibacterial and antifungal activities of these analogs against Staphylococcus aureus, Escherichia coli, and Aspergillus flavus were investigated. The structure-activity relationship study revealed that the length of the alkyl chain, as well as the type of substituent, has a dramatic impact on the antimicrobial activities. Particularly, the brominated analogs 3j with a nonyl side chain exhibited exceptional antifungal activities against A. flavus (half maximal inhibitory concentration (IC50) = 1.05 µg/mL), which surpassed that of the amphotericin B used as a positive control. The antibacterial activity against S. aureus, although not as potent, showed a similar trend to the antifungal activity. The data suggest that the 4-hydroxy-2-quinolone is a promising framework for the further development of new antimicrobial agents, especially for antifungal treatment.

Volatile Chemical Composition, Antibacterial and Antifungal Activities of Extracts from Different Parts of Globba schomburgkii Hook.f.

Globba schomburgkii Hook.f. is an ornamental plant that has recently found increasing demand as cut flowers, hence generating a significant number of by-products from different parts of the plant. To investigate the further applications of these by-products, twelve crude extracts from rhizomes, stalks, leaves, and flowers were prepared by serial exhaustive extraction. The volatile composition of these extracts was analyzed by GC/MS; a total of 89 compounds were identified, most of which were sesquiterpenes as well as some labdane-type diterpenes. The antimicrobial activities of these extracts were evaluated, revealing a correlation between the terpenoid content and antibacterial activities. Notably, the dichloromethane extracts of rhizomes and flowers, which contained the highest amount of terpenoids (e. g., α-gurjunene, guaia-9,11-diene, γ-bicyclohomofarnesal, ß-caryophyllene, and caryophyllene oxide), displayed the most prominent antibacterial activities. This work demonstrates the potential use of the crude extracts from G. schomburgkii as natural antibacterial ingredients for pharmaceutical and other applications.

The Inhibitory Effect of Validamycin A on Aspergillus flavus.

Aspergillus flavus is one of the most common isolates from patients with fungal infections. Aspergillus infection is usually treated with antifungal agents, but side effects of these agents are common. Trehalase is an essential enzyme involved in fungal metabolism, and the trehalase inhibitor, validamycin A, has been used to prevent fungal infections in agricultural products. In this study, we observed that validamycin A significantly increased trehalose levels in A. flavus conidia and delayed germination, including decreased fungal adherence. In addition, validamycin A and amphotericin B showed a combinatorial effect on A. flavus ATCC204304 and clinical isolates with high minimum inhibitory concentrations (MICs) of amphotericin B using checkerboard assays. We observed that validamycin A and amphotericin B had a synergistic effect on A. flavus strains resistant to amphotericin B. The MICs in the combination of validamycin A and amphotericin B were at 0.125 µg/mL and 2 µg/mL, respectively. The FICI of validamycin A and amphotericin B of these clinical isolates was about 0.25-0.28 with synergistic effects. No drug cytotoxicity was observed in human bronchial epithelial cells treated with validamycin A using LDH-cytotoxicity assays. In conclusion, this study demonstrated that validamycin A inhibited the growth of A. flavus and delayed conidial germination. Furthermore, the combined effect of validamycin A with amphotericin B increased A. flavus killing, without significant cytotoxicity to human bronchial epithelial cells. We propose that validamycin A could potentially be used in vivo as an alternative treatment for A. flavus infections.