Pontoriero Ana, Mosconi Natalia, Monti Laura, Bellú Sebastián, Williams Patricia A M, Raimondi Marcela, Lima Beatriz, Feresin Gabriela Egly, Nerli Bibiana, Rizzotto Marcela
Instituto de Química Rosario (IQUIR, CONICET, UNR), Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, 2000 Rosario, Argentina.
Centro de Química Inorgánica (CEQUINOR, CONICET, UNLP), Departamento de Química, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, 47 y 115- C.C.962- (B1900AVV), 1900, La Plata, Argentina.
Chem Biol Interact. 2017 Dec 25;278:152-161. doi: 10.1016/j.cbi.2017.10.004. Epub 2017 Oct 5.
The emergence of old and new antibiotic resistance created in the last decades revealed a substantial medical need for new classes of antimicrobial agents. The antimicrobial activity of sulfa drugs is often enhanced by complexation with metal ions, which is in concordance with the well-known importance of metal ions in biological systems. Besides, sulfonamides and its derivatives constitute an important class of drugs, with several types of pharmacological agents possessing antibacterial, anti-carbonic anhydrase, diuretic, hypoglycemic, antithyroid, antiviral and anticancer activities, among others. The purpose of this work has been the obtainment, characterization and determination of biological properties (antibacterial, antifungal, mutagenicity and phytotoxicity) of a new Co(III)-sulfathiazole complex: Costz, besides of its interaction with bovine serum albumin (BSA). The reaction between sodium sulfathiazole (Nastz) and cobalt(II) chloride in the presence of HO leads to a brown solid, [Co(stz)OH(HO)], (Costz). The structure of this compound has been examined by means of elemental analyses, FT-IR, H NMR, UV-Visible spectrometric methods and thermal studies. The Co(III) ion, which exhibits a distorted octahedral environment, could coordinate with the N thiazolic atom of sulfathiazolate. The complex quenched partially the native fluorescence of bovine serum albumin (BSA), suggesting a specific interaction with the protein. The Costz complex showed, in vitro, a moderate antifungal activity against Aspergillus fumigatus and A. flavus. As antibacterial, Costz displayed, in vitro, enhanced activity respective to the ligand against Pseudomonas aeruginosa. Costz did not show mutagenic properties with the Ames test. In the Allium cepa test the complex showed cytotoxic properties but not genotoxic ones. These results may be auspicious, however, further biological studies are needed to consider the complex Costz as a possible drug in the future.
过去几十年中出现的新老抗生素耐药性表明,医学上迫切需要新型抗菌剂。磺胺类药物与金属离子络合后,其抗菌活性往往会增强,这与金属离子在生物系统中的重要性是一致的。此外,磺胺类及其衍生物是一类重要的药物,多种药理剂具有抗菌、抗碳酸酐酶、利尿、降血糖、抗甲状腺、抗病毒和抗癌等活性。本研究的目的是获得一种新型Co(III)-磺胺噻唑配合物(Costz),对其进行表征和测定其生物学性质(抗菌、抗真菌、致突变性和植物毒性),并研究其与牛血清白蛋白(BSA)的相互作用。磺胺噻唑钠(Nastz)与氯化钴(II)在HO存在下反应生成棕色固体[Co(stz)OH(HO)](Costz)。通过元素分析、傅里叶变换红外光谱(FT-IR)、核磁共振氢谱(H NMR)、紫外可见光谱法和热分析等手段对该化合物的结构进行了研究。呈现扭曲八面体环境的Co(III)离子可与磺胺噻唑的N噻唑原子配位。该配合物部分猝灭了牛血清白蛋白(BSA)的天然荧光,表明与该蛋白质存在特异性相互作用。Costz配合物在体外对烟曲霉和黄曲霉显示出中等抗真菌活性。作为抗菌剂,Costz在体外对铜绿假单胞菌的活性相对于配体有所增强。Costz在艾姆斯试验中未显示致突变性。在洋葱根尖试验中,该配合物显示出细胞毒性但无遗传毒性。然而,这些结果可能是有利的,不过还需要进一步的生物学研究,以考虑将Costz配合物作为未来可能的药物。