Lee A R, Huang W H
School of Pharmacy, National Defense Medical Center, Taipei, Taiwan, R.O.C.
J Pharm Pharmacol. 1995 Jun;47(6):503-9. doi: 10.1111/j.2042-7158.1995.tb05839.x.
Two new zinc sulphadiazine (Zn(SD)2)-amine complexes, zinc sulphadiazine-methylamine (Zn(SD)2(CH3NH2)2) and zinc sulphadiazine-ethylenediamine (Zn(SD)2(C2H8N2)3.H2O), were prepared and compared with silver sulphadiazine (AgSD). The compounds were readily obtained by reaction of zinc nitrate hexahydrate with sulphadiazine or its salt in methylamine and ethylenediamine, respectively. Structure was established by X-ray crystallography and ultraviolet-visible, infrared and nuclear magnetic resonance spectroscopy. The products were effective, in-vitro, against Gram-positive and Gram-negative bacteria as well as fungus. However, their activity is partially reversed by p-aminobenzoic acid. Further investigations in burned mice revealed that these compounds displayed a potential value in the prevention and treatment of wound healing, and diminution of mortality and weight loss. The toxicity of Zn(SD)2 derivatives was much lower than that of AgSD. The better aqueous solubility and skin permeability may explain the reason for their superiority over AgSD in the efficacy for topical therapy. Zn(SD)2(CH3NH2)2 was consistently more potent and was chosen for further development in clinical uses. The similarity in complexation between Zn(SD)2(CH3NH2)2 and AgSD may be significant to distinguish that from any other Zn(SD)2 derivative in bioactivity.
制备了两种新型磺胺嘧啶锌（Zn(SD)2）-胺配合物，即磺胺嘧啶锌-甲胺（Zn(SD)2(CH3NH2)2）和磺胺嘧啶锌-乙二胺（Zn(SD)2(C2H8N2)3.H2O），并与磺胺嘧啶银（AgSD）进行了比较。这些化合物分别通过六水合硝酸锌与磺胺嘧啶或其盐在甲胺和乙二胺中的反应轻松获得。通过X射线晶体学以及紫外-可见光谱、红外光谱和核磁共振光谱确定了结构。这些产物在体外对革兰氏阳性菌、革兰氏阴性菌以及真菌均有效。然而，它们的活性会被对氨基苯甲酸部分逆转。对烧伤小鼠的进一步研究表明，这些化合物在伤口愈合的预防和治疗以及降低死亡率和体重减轻方面显示出潜在价值。Zn(SD)2衍生物的毒性远低于AgSD。更好的水溶性和皮肤渗透性可能解释了它们在局部治疗效果上优于AgSD的原因。Zn(SD)2(CH3NH2)2始终表现出更强的效力，并被选择用于临床应用的进一步开发。Zn(SD)2(CH3NH2)2与AgSD在络合方面的相似性对于在生物活性方面将其与任何其他Zn(SD)2衍生物区分开来可能具有重要意义。
