Department of Medicinal Chemistry, School of Pharmacy, University of Medicine and Pharmacy at Ho Chi Minh City, 41 Dinh Tien Hoang, Dist. 1, Ho Chi Minh City, Viet Nam.
Bioorg Med Chem Lett. 2012 Jul 15;22(14):4555-60. doi: 10.1016/j.bmcl.2012.05.112. Epub 2012 Jun 6.
A total of 30 chalcone analogues was synthesized via a base catalyzed Claisen Schmidt condensation and screened for their in vitro antibacterial activity against Methicillin-sensitive Staphylococcus aureus (MSSA) and Methicillin-resistant Staphylococcus aureus (MRSA) alone or in combination with non beta-lactam antibiotics namely ciprofloxacin, chloramphenicol, erythromycin, vancomycin, doxycycline and gentamicin. In the checkerboard technique, fractional inhibitory concentration indices (FICI) show that the following combinations like ciprofloxacin with 25 (4'-bromo-2-hydroxychalcone); doxycycline with 21 (4-hydroxychalcone); doxycycline with 25; and doxycycline with 4 (2',2-dihydroxychalcone) were synergistic against MRSA. In term SAR study, the relationship between chalcone structure and their antibacterial activity against S. aureus and synergy with tested antibiotics were discussed. Possible mechanisms for antibacterial activity of chalcones alone as well as the synergistic effect in combinations were proposed by molecular modeling studies, respectively. Combinations of chalcones with conventional antibiotics could be an effective alternative in the treatment of infection caused by MRSA.
共合成了 30 种查尔酮类似物，通过碱催化的 Claisen-Schmidt 缩合反应进行合成，并单独或与非β-内酰胺抗生素（如环丙沙星、氯霉素、红霉素、万古霉素、强力霉素和庆大霉素）一起筛选其对甲氧西林敏感金黄色葡萄球菌（MSSA）和甲氧西林耐药金黄色葡萄球菌（MRSA）的体外抗菌活性。在棋盘技术中，部分抑制浓度指数（FICI）表明，以下组合具有协同作用，如环丙沙星与 25（4′-溴-2-羟基查尔酮）；强力霉素与 21（4-羟基查尔酮）；强力霉素与 25；以及强力霉素与 4（2′，2-二羟基查尔酮）对 MRSA 具有协同作用。在 SAR 研究中，讨论了查尔酮结构与它们对金黄色葡萄球菌的抗菌活性以及与测试抗生素的协同作用之间的关系。通过分子建模研究分别提出了查尔酮单独的抗菌活性以及组合中的协同作用的可能机制。查尔酮与传统抗生素的组合可能是治疗 MRSA 引起的感染的有效替代方法。
