Abstract：
Antimicrobial resistance has become a global threat to human health, which is coupled with the lack of novel drugs. Metallocompounds have emerged as promising diverse scaffolds for the development of new antibiotics. Herein, we prepared some metal compounds mainly focusing on cis-[Ru(bpy)(dppz)(SO3)(NO)](PF6) (PR02, bpy = 2,2\'-bipyridine, dppz = dipyrido[3,2-a:2\',3\'-c]phenazine), in which phenazinic and nitric oxide ligands along with sulfite conferred some key properties. This compound exhibited a redox potential for bound NO+/0 of -0.252 V (vs. Ag|AgCl) and a high pH for nitrosyl-nitro conversion of 9.16, making the nitrosyl ligand the major species. These compounds were still able to bind to DNA structures. Interestingly, reduced glutathione (GSH) was unable to promote significant NO/HNO release, an uncommon feature of many similar systems. However, this reducing agent was essential to generate superoxide radicals. Antimicrobial studies were carried out using six bacterial strains, where none or very low activity was observed for Gram-negative bacteria. However, PR02 and PR (cis-[Ru(bpy)(dppz)Cl2]) showed high antibacterial activity in some Gram-positive strains (MBC for S. aureus up to 4.9 μmol L-1), where the activity of PR02 was similar to or at least 4-fold better than that of PR. Besides, PR02 showed capacity to inhibit bacterial biofilm formation, a major health issue leading to bacterial tolerance to antibiotics. Interestingly, we also showed that PR02 can function in synergism with the known antibiotic ampicillin, improving their action up to 4-fold even against resistant strains. Altogether, these results showed that PR02 is a promising antimicrobial nitrosyl ruthenium compound combining features beyond its killing action, which deserves further biological studies.
摘要：
抗菌素耐药性已成为威胁人类健康的全球性问题,再加上缺乏新药。金属化合物已成为开发新抗生素的有希望的多种支架。在这里，我们制备了一些金属化合物，主要集中在顺式-[Ru（bpy）（dppz）（SO3）（NO）]（PF6）（PR02，bpy=2,2'-联吡啶，dppz=二吡啶[3,2-a:2\'，3\'-c]吩嗪)，其中菲嗪和一氧化氮配体以及亚硫酸盐赋予了一些关键性质。该化合物对结合的NO+/0表现出-0.252V的氧化还原电势（与Ag|AgCl）和亚硝酰-硝基转化的高pH值为9.16，使亚硝酰配体成为主要物种。这些化合物仍然能够与DNA结构结合。有趣的是,还原型谷胱甘肽（GSH）不能促进显著的NO/HNO释放，许多类似系统的罕见特征。然而,这种还原剂对产生超氧自由基至关重要。使用六种细菌菌株进行了抗菌研究，其中对于革兰氏阴性细菌没有观察到或观察到非常低的活性。然而,PR02和PR（顺式-[Ru（bpy）（dppz）Cl2]）在某些革兰氏阳性菌株（金黄色葡萄球菌的MBC高达4.9μmolL-1）中显示出高抗菌活性，其中PR02的活性与PR相似或比PR好至少4倍。此外,PR02显示出抑制细菌生物膜形成的能力，导致细菌对抗生素耐受的主要健康问题。有趣的是,我们还表明，PR02可以与已知的抗生素氨苄青霉素协同作用，提高他们的作用高达4倍，甚至对耐药菌株。总之,这些结果表明，PR02是一种有前途的抗菌亚硝酰钌化合物，结合了其杀伤作用之外的特征，这值得进一步的生物学研究。
