Ozaki M, Matsuda M, Tomii Y, Kimura K, Kazuno K, Kitano M, Kise M, Shibata K, Otsuki M, Nishino T
Biology Laboratories, Nippon Shinyaku Co., Ltd., Kyoto, Japan.
Antimicrob Agents Chemother. 1991 Dec;35(12):2490-5. doi: 10.1128/AAC.35.12.2490.
NM394 is a new 6-fluoroquinolone antibacterial agent with a tricyclic structure which has a bridge that connects the N-1 and C-2 positions of the quinolone. The antibacterial activity of NM394 against clinical isolates of staphylococci, streptococci, enterococci, members of the family Enterobacteriaceae, and Pseudomonas aeruginosa was equal to or one-half that of ciprofloxacin. NM394 was as active as ofloxacin against gram-positive bacteria and was two to eight times more active against gram-negative bacteria, including P. aeruginosa. NM394 was two to eight times more active than enoxacin against gram-positive and gram-negative bacteria. The MICs of NM394 against Escherichia coli and P. aeruginosa at pH 5.5 were reduced 4 to 16 times compared with those at pH 7.0. Ciprofloxacin, ofloxacin, and enoxacin were 2 to 32 times less active against these two bacteria and Staphylococcus aureus at an acidic pH than they were at pH 7.0. In the presence of 5 mM Mg2+, the MICs of all of these drugs increased 2 to 32 times, but they were only slightly affected by 5 mM Ca2+, type of medium, serum, or size of inoculum. NM394 showed potent bactericidal activity and inhibited the supercoiling activity of E. coli DNA gyrase. The in vitro antibacterial profile of NM394 is similar to that of other 6-fluoroquinolones.
NM394是一种新型的具有三环结构的6-氟喹诺酮类抗菌剂，其具有连接喹诺酮N-1和C-2位的桥。NM394对葡萄球菌、链球菌、肠球菌、肠杆菌科成员及铜绿假单胞菌临床分离株的抗菌活性与环丙沙星相当或为其一半。NM394对革兰氏阳性菌的活性与氧氟沙星相当，对包括铜绿假单胞菌在内的革兰氏阴性菌的活性比氧氟沙星高2至8倍。NM394对革兰氏阳性菌和革兰氏阴性菌的活性比依诺沙星高2至8倍。与pH 7.0时相比，NM394在pH 5.5时对大肠杆菌和铜绿假单胞菌的最低抑菌浓度降低了4至16倍。在酸性pH条件下，环丙沙星、氧氟沙星和依诺沙星对这两种细菌及金黄色葡萄球菌的活性比在pH 7.0时低2至32倍。在存在5 mM Mg2+的情况下，所有这些药物的最低抑菌浓度增加了2至32倍，但它们仅受到5 mM Ca2+、培养基类型、血清或接种量大小的轻微影响。NM394表现出强大的杀菌活性并抑制大肠杆菌DNA促旋酶的超螺旋活性。NM394的体外抗菌谱与其他6-氟喹诺酮类药物相似。
