Enhanced fermentation with Lactiplantibacillus plantarum improved coffee flavor by changing microbial communities and organic compounds of Coffea arabica

作者: Zhang, Jilai ; Liu, Kunyi ; Zheng, Jia ; Li, Xingyu ; Yin, Zhiheng ; Yuan, Wenjuan ; Zheng, Tingting ; Wang, Qi ; Shen, Xiaojing

Coffee is a globally favored beverage due to its attractive and complex flavor.Comprehensive anal. employing high-throughput sequencing, UHPLC-MS/MS, HS-SPME-GC-MS and Specialty Coffee Association cupping protocol, revealed the beneficial effects of enhanced fermentation with Lactiplantibacillus plantarum on coffee flavor and microbial communities of Coffea arabica.Gene sequencing showed that the predominant microorganisms at a general level were Lactobacillus, Weissella, Trichococcus for bacteria, and Hanseniaspora, Lachancea and Pichia for fungi.Meanwhile, 156 and 65 differentially changed non-volatile organic compounds (DCn-VOCs) were identified between LE2 (enhanced fermentation with L. plantarum at 18 h) vs. LB2 (un-enhanced fermentation at 18 h), and LE3 (enhanced fermentation with L. plantarum at 36 h) vs. LB3 (un-enhanced fermentation at 36 h), resp.Furthermore, 25 differentially changed volatile organic compounds (DCVOCs) were found between LE (enhanced fermentation with L. plantarum) and LB (un-enhanced fermentation), including 16 up-regulated and 9 down-regulated DCVOCs.The coffee flavor had a neg. correlation with 2-acetyl-pyrroline and 4-ethyl-benaldehyde, while a pos. correlation with isopentyl hexanoate. 2-heptanol had a pos. correlation with 2-hexyl-thiophene and Bu benzoate, while 2,3-hexanedione was pos. correlated with 2-hexyl-thiophene.Therefore, the enhanced fermentation with L. plantarum inhibited the growth of other microorganisms, and changed the organic compounds during coffee fermentation

2024-12-01·European Journal of Medicinal Chemistry

Discovery of highly potent triazole derivatives with broad-spectrum antifungal activity based on Iodiconazole

Article

作者: Zhao, Dongmei ; Cheng, Maosheng ; Liu, Rui ; Luo, Zirui ; Zhang, Jiachen ; Yin, Wenbo ; Gao, Zixuan ; Wu, Xudong ; Sun, Yixiang ; Qin, Qiaohua ; Zhang, Haoyu ; Li, Kejian ; Liu, Rongrong ; Su, Xin ; Liu, Nian

The widespread use of broad-spectrum antibiotics, the growing number of immunocompromised individuals, and the emergence of drug-resistant strains have resulted in the increasing incidence and mortality of invasive fungal infections. Azole drugs are the primary treatment for invasive fungal infections, and Iodiconazole is a potent azole drug with strong antifungal activity, but its stability is poor. In order to improve stability, a series of triazole compounds containing ethynyl group were designed and synthesized. Most of the compounds showed strong inhibitory activity against pathogenic fungi, among which compound 20l showed excellent inhibitory activity against pathogenic fungi and drug-resistant fungi. Importantly, and the stability of 20l (T_1/2 = 30.2 min) was obviously improved compared with Iodiconazole (T_1/2 = 4.39 min). In addition, the preferred compound 20l can prevent fungal phase transition and the formation of fungal biofilm, and show satisfactory fungicidal activity. In addition, the compound 20l was almost non-toxic to mammalian HUVEC cell and 293T cell. In vivo pharmacokinetic studies showed that 20l had acceptable pharmacokinetic properties. These results strongly demonstrate that compound 20l was worth further investigation as a potential antifungal inhibitor.

2024-12-01·Bioorganic Chemistry

Design, synthesis and bioactivity evaluation of triazole antifungal drugs with phenylthiophene structure

Article

作者: Liu, Rongrong ; Gao, Zixuan ; Wu, Xudong ; Sun, Yixiang ; Cheng, Maosheng ; Zhang, Jiachen ; Zhang, Guoqi ; Zhao, Dongmei ; Luo, Zirui ; Zhang, Haoyu ; Li, Kejian ; Su, Xin ; Qin, Qiaohua ; Liu, Nian

Invasive fungal infections have high morbidity and mortality rates and have become one of the most serious threats to human health. In the present study, a series of triazole antifungal derivatives with phenylthiophene backbone were obtained by structural modification of the lead compound using Iodiconazole as the lead compound. Among them, compound 19g is a triazole antifungal compound with 4-chloro-2-fluoro phenylthiophene backbone, which showed optimal antifungal activity against Candida albicans, Cryptococcus neoformans, and Aspergillus, with a MIC₈₀ value of 0.0625 μg/mL. In addition, compounds 19e, 19f, 19g, 19h, 19i and 19k exhibited different levels of inhibitory activity against fluconazole-resistant strains with MIC₈₀ values ranging from 0.0625 μg/mL to 32 μg/mL. Since compound 19g had optimal in vitro antifungal activity, we selected 19g for human liver microsomal stability and CYP enzyme inhibition assays as well as further evaluated the inhibitory activity of compound 19g on normal and cancerous cells in humans. Finally, we verified the inhibitory effect of compound 19g on the filamentation of Candida albicans and determined the mechanism of action by sterol composition analysis.

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