Inorganic Chemistry Laboratory, Department of Chemistry, University of Ioannina, 45110 Ioannina, Greece.
Inorganic Chemistry Laboratory, Department of Chemistry, University of Ioannina, 45110 Ioannina, Greece.
J Inorg Biochem. 2018 Apr;181:41-55. doi: 10.1016/j.jinorgbio.2018.01.004. Epub 2018 Feb 3.
The known metallotherapeutic [Ag(salH)] (AGSAL-1) of salicylic acid (salH), was used for the development of new efficient silver based material for wounds healing. AGSAL-1 was characterized by spectroscopic techniques and X-ray crystallography. The wound healing epithelialization of AGSAL-1 was investigated by the means of scratch assay against immortalized human keratinocytes (HaCaT) cells. The anti-inflammatory activity of AGSAL-1 was evaluated by monitoring the catalytic peroxidation of linoleic acid to hydroperoxylinoleic acid by the enzyme lipoxygenase (LOX). The antibacterial activity of AGSAL-1 was evaluated against bacterial species which colonize wounds, such as: Pseudomonas aeruginosa (PAO1), Staphylococcus epidermidis and Staphylococcus aureus, by the means of Minimum Inhibitory Concentration (MIC), Minimum Bactericidal Concentration (MBC) and their Inhibition Zone (IZ). Moreover, the influence of AGSAL-1 against the formation of biofilm of PAO1 and St. aureus was also evaluated by the mean of Biofilm Elimination Concentration (ΒΕC). A hydrogel material CMC@AGSAL-1, based on the dispersion of AGSAL-1 in to carboxymethyl cellulose (CMC) was tested for its antimicrobial activity. Molecular Docking was performed, to explore the molecular interaction of AGSAL-1 with (i) the transcriptional regulator of PAO1, LasR. (ii) the mevalonate pathway for the biosynthesis of isoprenoids which is essential for gram-positive bacteria St. epidermidis and St. aureus. The toxicity of AGSAL-1 was examined against the HaCaT cells. Its genotoxicity was evaluated using Allium cepa model, in vivo. No genotoxicity was detected, indicating that AGSAL-1 is a candidate towards the development on a new efficient medication of the silver based metallodrugs.
已知水杨酸的金属治疗剂 [Ag(salH)]（AGSAL-1）被用于开发用于伤口愈合的新型高效银基材料。AGSAL-1 采用光谱技术和 X 射线晶体学进行了表征。通过划痕试验研究了 AGSAL-1 对永生化人角质形成细胞（HaCaT）细胞的伤口愈合上皮化作用。通过监测脂氧合酶（LOX）催化亚油酸向过氧亚油酸的过氧化作用，评估了 AGSAL-1 的抗炎活性。通过最低抑菌浓度（MIC）、最低杀菌浓度（MBC）及其抑菌圈（IZ）评估了 AGSAL-1 对定植于伤口的细菌物种（如铜绿假单胞菌（PAO1）、表皮葡萄球菌和金黄色葡萄球菌）的抗菌活性。此外，还通过生物膜消除浓度（ΒΕC）评估了 AGSAL-1 对 PAO1 和金黄色葡萄球菌生物膜形成的影响。基于 AGSAL-1 在羧甲基纤维素（CMC）中的分散体的水凝胶材料 CMC@AGSAL-1 进行了其抗菌活性测试。进行了分子对接，以研究 AGSAL-1 与（i）PAO1 的转录调节剂 LasR 之间的分子相互作用。（ii）用于合成异戊烯的甲羟戊酸途径，这对于革兰氏阳性细菌表皮葡萄球菌和金黄色葡萄球菌是必不可少的。AGSAL-1 的毒性通过 HaCaT 细胞进行了检查。使用洋葱表皮模型在体内评估了其遗传毒性。未检测到遗传毒性，表明 AGSAL-1 是开发新型高效银基金属药物的候选药物。
