Conjugation of Penicillin-G with Silver(I) Ions Expands Its Antimicrobial Activity against Gram Negative Bacteria
Conjugation of Penicillin-G with Silver(I) Ions Expands Its Antimicrobial Activity against Gram Negative Bacteria
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DOI：
10.3390/antibiotics9010025
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发表时间：
2020-01-01
影响因子：
4.8
通讯作者：
Hadjikakou, Sotiris K.
中科院分区：
文献类型：
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作者：
Ketikidis, Ioannis;Banti, Christina N.;Hadjikakou, Sotiris K.
青霉素G（PenH）与银（I）离子的缀合形成具有式[Ag（pen）（CH 3OH）]（2）（PenAg）的新CoMeD（金属与药物的缀合物）。PenAg通过大量的物理和光谱技术表征，其包括固态m. p.;元素分析; X射线荧光（XRF）光谱;扫描电子显微镜（SEM）;能量色散X射线光谱（EDX）; FT-IR;以及在溶液中：衰减全反射光谱（FT-IR-ATR）、UV-Vis、H-1 NMR和原子吸收（AA）。通过NMR光谱确定PenAg的结构。银（I）离子与PenH的羧基配位，而次级分子内相互作用通过（i）MeOD-d（4）中酰胺基的氮原子或（ii）氘代二甲亚砜DMSO-d（6）中硫杂环丁烷环中的硫原子产生。PenAg和青霉素钠盐（PenNa）（临床使用的制剂）对革兰氏阳性菌（表皮葡萄球菌（S.表皮葡萄球菌）和金黄色葡萄球菌（S.通过最小抑菌浓度（MIC）、最小杀菌浓度（MBC）和抑菌圈（IZ）来评价革兰氏阴性菌（铜绿假单胞菌（P. aeuroginosa PAO 1））。PenAg抑制革兰氏阴性细菌菌株铜绿假单胞菌的生长，MIC值为23.00 +/- 2.29 μ M，与PenNa相反，PenNa没有显示这种活性（>2 mM）。PenAg对革兰氏阳性菌S.表皮葡萄球菌和表皮葡萄球菌。金葡菌甚至比PenNa更好。此外，PenAg在高达300 μ M的浓度下对卤虫没有体内毒性。治疗窗宽和毒性低，使PenAg成为开发新抗生素的可能候选者。
Conjugation of penicillin G (PenH) with silver(I) ions forms a new CoMeD (conjugate of metal with a drug) with formula [Ag(pen)(CH3OH)](2) (PenAg). PenAg was characterized by a plethora of physical and spectroscopic techniques, which include in the solid state m.p.; elemental analysis; X-ray fluorescence (XRF) spectroscopy; scanning electron microscopy (SEM); energy-dispersive X-ray spectroscopy (EDX); FT-IR; and in solution: attenuated total reflection spectroscopy (FT-IR-ATR), UV-Vis, H-1 NMR, and atomic absorption (AA). The structure of PenAg was determined by NMR spectroscopy. Silver(I) ions coordinate to the carboxylic group of PenH, while secondary intra-molecular interactions are developed through (i) the nitrogen atom of the amide group in MeOD-d(4) or (ii) the sulfur atom in the thietane ring in deuterated dimethyl sulfoxide DMSO-d(6). The antibacterial activities of PenAg and the sodium salt of penicillin (PenNa) (the formulation which is clinically used) against Gram positive (Staphylococcus epidermidis (S. epidermidis) and Staphylococcus aureus (S. aureus)) and Gram negative (Pseudomonas aeruginosa (P. aeuroginosa PAO1)) bacteria were evaluated by the means of minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and inhibition zone (IZ). PenAg inhibits the growth of the Gram negative bacterial strain P. aeuroginosa with a MIC value of 23.00 +/- 2.29 mu M, in contrast to PenNa, which shows no such activity (>2 mM). The corresponding antimicrobial activities of PenAg against the Gram positive bacteria S. epidermidis and S. aureus are even better than those of PenNa. Moreover, PenAg exhibits no in vivo toxicity against Artemia salina at concentration up to 300 mu M. The wide therapeutic window and the low toxicity, make PenAg a possible candidate for the development of a new antibiotic.