Zinc sulphadiazines: novel topical antimicrobial agents for burns.
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.
Lee
A R
AR
School of Pharmacy, National Defense Medical Center, Taipei, Taiwan, R.O.C.
Huang
W H
WH
D000818:Animals; D001419:Bacteria / Q000187:drug effects; D002056:Burns / Q000188:drug therapy*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D018360:Crystallography, X-Ray; D008297:Male; D051379:Mice; D008826:Microbial Sensitivity Tests; D010539:Permeability; D011552:Pseudomonas Infections / Q000517:prevention & control; D051381:Rats; D017207:Rats, Sprague-Dawley; D012837:Silver Sulfadiazine / Q000494:pharmacology / Q000627:therapeutic use*; D013411:Sulfadiazine / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D015430:Weight Gain / Q000187:drug effects; D014946:Wound Infection / Q000517:prevention & control; D015032:Zinc / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*
D013411:Sulfadiazine; D015032:Zinc; D012837:Silver Sulfadiazine