Key Laboratory of Drug Targeting and Drug Delivery Systems of the Ministry of Education, Department of Medicinal Natural Products, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
Mar Drugs. 2013 Aug 15;11(8):2927-48. doi: 10.3390/md11082927.
Methicillin-resistant Staphylococcus aureus (MRSA) continues to be a major problem, causing severe and intractable infections worldwide. MRSA is resistant to all beta-lactam antibiotics, and alternative treatments are limited. A very limited number of new antibiotics have been discovered over the last half-century, novel agents for the treatment of MRSA infections are urgently needed. Marinopyrrole A was reported to show antibiotic activity against MRSA in 2008. After we reported the first total synthesis of (±)-marinopyrrole A, we designed and synthesized a series of marinopyrrole derivatives. Our structure activity relationship (SAR) studies of these novel derivatives against a panel of Gram-positive pathogens in antibacterial assays have revealed that a para-trifluoromethyl analog (33) of marinopyrrole A is ≥ 63-, 8-, and 4-fold more potent than vancomycin against methicillin-resistant Staphylococcus epidermidis (MRSE), methicillin-susceptible Staphylococcus aureus (MSSA) and MRSA, respectively. The results provide valuable information in the search for new-generation antibiotics.
耐甲氧西林金黄色葡萄球菌（MRSA）仍然是一个主要问题，在全球范围内导致严重且难以治疗的感染。MRSA 对所有β-内酰胺类抗生素都有耐药性，替代治疗方法有限。在过去的半个世纪中，发现的新抗生素非常有限，因此迫切需要新型药物来治疗 MRSA 感染。2008 年，报道了 Marinopyrrole A 对 MRSA 具有抗生素活性。在我们首次报道（±）-Marinopyrrole A 的全合成后，我们设计并合成了一系列 Marinopyrrole 衍生物。我们对这些新型衍生物进行了针对一组革兰氏阳性病原体的抗菌测定中的构效关系（SAR）研究，结果表明 Marinopyrrole A 的对位三氟甲基类似物（33）对耐甲氧西林表皮葡萄球菌（MRSE）、甲氧西林敏感金黄色葡萄球菌（MSSA）和 MRSA 的活性分别比万古霉素强 63 倍、8 倍和 4 倍。这些结果为寻找新一代抗生素提供了有价值的信息。
