重新利用亚醇来解决与线索利德相关的血清性毒性,以对抗多药耐药结核病
Rukaiyya T Girase1, Iqrar Ahmad1, Jong Min Oh2
1Department of Pharmaceutical Chemistry, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Maharashtra India, 4254.
ACS medicinal chemistry letters
|December 20, 2023
概括
克洛特里马在治疗耐药结核病 (TB) 方面表现有前途,通过匹配Linezolid.
科学领域:
- 药用化学 医学化学
- 微生物学 微生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 结核病 (TB) 药物Linezolid的血清毒性源于抑制单胺氧化酶 (MAO) 酶.
- 在结构上与线索利德相似的阿醇化合物是对抗耐药结核病的重新利用的潜在候选者.
- 研究用于结核病治疗的醇的目的是寻找具有降低MAO抑制和相关毒性的替代品.
研究的目的:
- 重新利用阿醇抗真菌药物 (波萨可纳,伊特拉可纳,米可纳,克洛特里马) 用于治疗耐药结核病 (TB).
- 评估这些醇对Mycobacterium tuberculosis (Mtb) 菌株的疗效.
- 评估醇在节约单胺氧化酶 (MAO) 酶中的选择性,从而降低血清毒性.
主要方法:
- 对抗结核病活性进行阿醇化合物 (波萨可纳,伊特拉可纳,米可纳,克洛特里马) 的查.
- 确定活性化合物的最小抑制度 (MIC) 针对Mtb H37Rv菌株.
- 评估MIC50值与各种耐药的Mtb临床分离物相比.
- 评估化合物对MAO-A和MAO-B酶的抑制作用.
主要成果:
- 克洛特里马与线索利德 (MIC:2.26μM) 相比,对Mtb H37Rv表现出同等强的活性.
- 克洛特里马对耐药Mtb分离物,包括inHA促进物+,katG+,rpoB+和MDR菌株显示出有利的MIC50值.
- 与线索利德相比,克洛特里马对MAO-A (3.90倍) 和MAO-B (50.35倍) 的抑制显著减少.
结论:
- 克洛特里马是药物耐药结核病治疗的有希望的重用药物候选药物.
- 克洛特里马对Mtb的疗效和降低的MAO抑制表明,血清激素毒性的风险较低.
- 需要进一步研究克洛特里马作为结核病治疗中更安全的替代品.
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