Nielsen Simon F, Larsen Mogens, Boesen Thomas, Schønning Kristian, Kromann Hasse
Lica Pharmaceuticals A/S, Symbion Science Park, Fruebjergvej 3, DK-2100 Copenhagen, Denmark.
J Med Chem. 2005 Apr 7;48(7):2667-77. doi: 10.1021/jm049424k.
This paper describes how the introduction of "cationic" aliphatic amino groups in the chalcone scaffold results in potent antibacterial compounds. It is shown that the most favorable position for the aliphatic amino group is the 2-position of the B-ring, in particular in combination with a lipophilic substituent in the 5-position of the B-ring. We demonstrate that the compounds act by unselective disruption of cell membranes. Introduction of an additional aliphatic amino group in the A-ring results in compounds that are selective for bacterial membranes combined with a high antibacterial activity against both Gram-positive and -negative pathogens. The most potent compound in this study (78) has an MIC value of 2 muM against methicillin resistant Staphylococus aureus.
本文描述了在查尔酮骨架中引入“阳离子”脂肪族氨基如何产生强效抗菌化合物。结果表明，脂肪族氨基最有利的位置是B环的2位，特别是与B环5位的亲脂性取代基结合时。我们证明这些化合物通过非选择性破坏细胞膜起作用。在A环中引入额外的脂肪族氨基会产生对细菌膜具有选择性且对革兰氏阳性和阴性病原体均具有高抗菌活性的化合物。本研究中最有效的化合物（78）对耐甲氧西林金黄色葡萄球菌的最低抑菌浓度值为2μM。
