Barbarić Monika, Kraljević Sandra, Grce Magdalena, Zorc Branka
Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia.
Acta Pharm. 2003 Sep;53(3):175-86.
A new synthetic approach to the 1,2,5-oxadiazine ring system is described. 2-Substituted or 2,4-disubstituted 2H-1,2,5-oxadiazine-3,6(4H,5H)-dione derivatives 4 were prepared by cyclisation of hydroxamic acids 3 derived from N-(1-benzotriazolylcarbonyl)-amino acids 1. The structures of the synthesised compounds were fully characterised by IR, 1H and 13C NMR spectroscopy and elemental analysis. The aim of this study was to evaluate biological activity of the newly synthesised oxadiazine derivatives. Cytotoxic and cytostatic activities were tested on two cell lines (HeLa and GMK) and evaluated by MTT-test. Two human DNA viruses (adenovirus 7 and herpesvirus 1) and two human RNA viruses (coxsackievirus B5 and echovirus 7) were used in the antiviral test. Selected biological studies indicated that 2-phenyl- -2H-1,2,5-oxadiazine-3,6(4H,5H)-dione (4a) and 4-benzyl-2-phenyl-2H-1,2,5-oxadiazine-3,6(4H,5H)-dione (4c) statistically significantly inhibited cell growth. A minor antiviral effect was observed upon adenovirus, herpesvirus and enteroviruses.
描述了一种合成1,2,5-恶二嗪环系统的新方法。由N-(1-苯并三唑基羰基)-氨基酸1衍生的异羟肟酸3环化制备了2-取代或2,4-二取代的2H-1,2,5-恶二嗪-3,6(4H,5H)-二酮衍生物4。通过红外光谱、1H和13C核磁共振光谱以及元素分析对合成化合物的结构进行了全面表征。本研究的目的是评估新合成的恶二嗪衍生物的生物活性。在两种细胞系（HeLa和GMK）上测试了细胞毒性和细胞生长抑制活性，并通过MTT试验进行评估。在抗病毒试验中使用了两种人类DNA病毒（腺病毒7型和疱疹病毒1型）和两种人类RNA病毒（柯萨奇病毒B5型和埃可病毒7型）。选定的生物学研究表明，2-苯基-2H-1,2,5-恶二嗪-3,6(4H,5H)-二酮（4a）和4-苄基-2-苯基-2H-1,2,5-恶二嗪-3,6(4H,5H)-二酮（4c）在统计学上显著抑制细胞生长。对腺病毒、疱疹病毒和肠道病毒观察到轻微的抗病毒作用。
