Antibacterial and antibiofilm agents in the group of xanthone derivatives with piperazine moiety active against drug-resistant Helicobacter pylori strains

IF 4.5 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Bioorganic Chemistry Pub Date : 2024-08-30 DOI:10.1016/j.bioorg.2024.107755

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Abstract

Helicobacter pylori (H. pylori) cause chronic inflammation of the gastric mucosa which can lead to epithelial atrophy and metaplasia resulting in peptic ulcer disease and gastric cancer. The increasing resistance of H. pylori to antibiotics and chemotherapeutics used to treat the infection is a serious problem. However, it has been confirmed that the introduction of effective anti-H. pylori therapy can prevent the progression to cancerous changes. This problem calls for the search for new and effective therapies. Xanthones are a group of compounds with extensive biological activities, including antibacterial activity, also against H. pylori. Addressing this issue, the aim of the study was to evaluate the potential of a group of 13 xanthone derivatives against susceptible and resistant H. pylori strains. Moreover, our objective was to conduct tests aimed at determining their ability to inhibit biofilm formation.

The antimicrobial evaluation revealed that benzylpiperazine coupled at the C-2 position to xanthone (compounds C11 and C12) had good selective bacteriostatic activity against reference and clinical H. pylori strains (MBC/MIC ratio >4) but with no activity against other bacteria such as Staphylococcus aureus, Escherichia coli, and Lactobacillus paracasei. Analysis of the activity of compounds C11 and C12 against the biofilm formed by H. pylori strain ATCC 700684, and the clinical strain showed that these compounds caused a significant reduction in the amount of biofilm produced (5–20×). Moreover, cell viability analysis confirmed a 3–4× reduction in the viability of cells forming biofilm after treatment with C11 and C12. Finally, both compounds did not impair human fibroblast viability at tested concentrations and were not mutagenic in the Ames test. Therefore, they could be promising leads as antibacterial candidates for multidrug-resistant strains of H. pylori.

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具有哌嗪分子的黄酮衍生物类抗菌剂和抗生物膜剂，对抗药性幽门螺旋杆菌菌株具有活性。

幽门螺杆菌（H. pylori）会引起胃黏膜慢性炎症，导致上皮萎缩和变性，从而引发消化性溃疡病和胃癌。幽门螺杆菌对用于治疗感染的抗生素和化疗药物的耐药性越来越强，这是一个严重的问题。然而，已经证实，采用有效的抗幽门螺杆菌疗法可以防止幽门螺杆菌恶化为癌症。这一问题要求人们寻找新的有效疗法。氧杂蒽酮是一类具有广泛生物活性的化合物，其中包括抗菌活性，也能抗幽门螺杆菌。针对这一问题，本研究旨在评估一组 13 种黄酮衍生物对易感和耐药幽门螺杆菌菌株的抗菌潜力。此外，我们的目标是进行测试，以确定它们抑制生物膜形成的能力。抗菌评估结果表明，在 C-2 位与氧杂蒽酮偶联的苄基哌嗪（化合物 C11 和 C12）对参考和临床幽门螺杆菌菌株具有良好的选择性抑菌活性（MBC/MIC 比 >4），但对金黄色葡萄球菌、大肠杆菌和副卡西氏乳杆菌等其他细菌没有活性。化合物 C11 和 C12 对幽门螺杆菌菌株 ATCC 700684 和临床菌株形成的生物膜的活性分析表明，这些化合物能显著减少生物膜的生成量（5-20 倍）。此外，细胞存活率分析证实，经 C11 和 C12 处理后，形成生物膜的细胞存活率降低了 3-4倍。最后，在测试浓度下，这两种化合物都不会损害人类成纤维细胞的活力，在艾姆斯试验中也没有诱变性。因此，这两种化合物有望成为抗耐多药幽门螺杆菌菌株的候选抗菌药物。

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来源期刊

Bioorganic Chemistry 生物-生化与分子生物学

CiteScore

9.70

自引率

3.90%

发文量

679

审稿时长

31 days

期刊介绍： Bioorganic Chemistry publishes research that addresses biological questions at the molecular level, using organic chemistry and principles of physical organic chemistry. The scope of the journal covers a range of topics at the organic chemistry-biology interface, including: enzyme catalysis, biotransformation and enzyme inhibition; nucleic acids chemistry; medicinal chemistry; natural product chemistry, natural product synthesis and natural product biosynthesis; antimicrobial agents; lipid and peptide chemistry; biophysical chemistry; biological probes; bio-orthogonal chemistry and biomimetic chemistry. For manuscripts dealing with synthetic bioactive compounds, the Journal requires that the molecular target of the compounds described must be known, and must be demonstrated experimentally in the manuscript. For studies involving natural products, if the molecular target is unknown, some data beyond simple cell-based toxicity studies to provide insight into the mechanism of action is required. Studies supported by molecular docking are welcome, but must be supported by experimental data. The Journal does not consider manuscripts that are purely theoretical or computational in nature. The Journal publishes regular articles, short communications and reviews. Reviews are normally invited by Editors or Editorial Board members. Authors of unsolicited reviews should first contact an Editor or Editorial Board member to determine whether the proposed article is within the scope of the Journal.