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查尔酮席夫碱破坏酿酒酵母和白色念珠菌细胞膜的完整性。

Chalcone Schiff bases disrupt cell membrane integrity of Saccharomyces cerevisiae and Candida albicans cells.

机构信息

Department of Bioengineering, Gebze Technical University, 41400, Kocaeli, Turkey.

Department of Chemistry, Faculty of Sciences, Karadeniz Technical University, 61080, Trabzon, Turkey.

出版信息

Arch Microbiol. 2023 May 20;205(6):246. doi: 10.1007/s00203-023-03584-y.

Abstract

Chalcones have a variety of cellular protective and regulatory functions that may have therapeutic potential in many diseases. In addition, they are considered to affect key metabolic processes in pathogens. Nevertheless, our current knowledge of the action of these compounds against fungal cell is scarce. Therefore, in this study, various substituted chalcone Schiff bases were investigated to reveal their cellular targets within the yeasts Saccharomyces cerevisiae and Candida albicans. First, their antifungal activities were determined via minimum inhibitory concentration method. Surprisingly, parent chalcone Schiff bases showed little or no antifungal activity, while the nitro-substituted derivatives were found to be highly active against yeast cells. Next, we set out to determine the cellular target of active compounds and tested the involvement of the cell wall and cell membrane in this process. Our conductivity assay confirmed that the yeast cell membrane was compromised, and that ion leakage occurred upon treatment with nitro-substituted chalcone Schiff bases. Therefore, the cell membrane came to the fore as a possible target for the active chalcone derivatives. We also showed that exogenous ergosterol added to the growth medium reduced the inhibitory effect of chalcones. Our findings open up new possibilities for the design of future antimicrobial agents based on this appealing backbone structure.

摘要

查耳酮具有多种细胞保护和调节功能,在许多疾病中可能具有治疗潜力。此外,它们被认为会影响病原体中的关键代谢过程。然而,我们目前对这些化合物针对真菌细胞的作用知之甚少。因此,在这项研究中,研究了各种取代的查尔酮席夫碱,以揭示它们在酵母酿酒酵母和白色念珠菌中的细胞靶标。首先,通过最小抑菌浓度法测定它们的抗真菌活性。令人惊讶的是,母体查尔酮席夫碱几乎没有或没有抗真菌活性,而硝基取代的衍生物对酵母细胞表现出高度的活性。接下来,我们着手确定活性化合物的细胞靶标,并测试细胞壁和细胞膜在此过程中的参与。我们的电导率测定证实酵母细胞膜受损,并且在用硝基取代的查尔酮席夫碱处理时发生离子泄漏。因此,细胞膜成为活性查尔酮衍生物的可能靶标。我们还表明,在生长培养基中添加外源性麦角固醇可降低查尔酮的抑制作用。我们的发现为基于这种有吸引力的骨架结构设计未来的抗菌剂开辟了新的可能性。

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