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Synthesis, molecular modeling and antiviral activity of novel 5-fluoro-1H-indole-2,3-dione 3-thiosemicarbazones.
Bioorganic Chemistry ( IF 4.5 ) Pub Date : 2020-08-26 , DOI: 10.1016/j.bioorg.2020.104202
Zekiye Şeyma Sevinçli 1 , Gizem Nur Duran 2 , Mehmet Özbil 3 , Nilgün Karalı 4
Affiliation  

In this work, novel 5-fluoro-1-methyl/ethyl-1H-indole-2,3-dione 3-[4-(substituted phenyl)-thiosemicarbazones] 6a-n and 7a-n were synthesized. The antiviral effects of the compounds were tested against HSV-1 (KOS), HSV-2 (G) HSV-1 TK- KOS ACVr and VV in HEL cell cultures using acyclovir and ganciclovir as standards, and Coxsackie B4 virus in Vero cell cultures using ribavirin and mycophenolic acid as standards. R2 ethyl substituted 7 derivatives were found effective against viruses tested. R1 4-CF3 substituted 7d, R1 4-OCH3 substituted 7 g and R1 3-Cl substituted 7 l showed activity against HSV-1 (KOS), HSV-2 (G) HSV-1 TK- KOS ACVr and VV. Whereas only R1 4-Br substituted 7n has selective activity against coxsackie B4 virus. Molecular modeling studies of 7d and 7l were performed to determine binding side on HSV-1 glycoprotein B and D, HSV-2 glycoprotein B structures.



中文翻译:

新型5-氟-1H-吲哚-2,3-二酮3-硫代半氨基甲酮的合成,分子建模和抗病毒活性。

在这项工作中,合成了新颖的5-氟-1-甲基/乙基-1 H-吲哚-2,3-二酮3- [4-(取代的苯基)-硫代半脲酮] 6a-n7a-n。使用阿昔洛韦和更昔洛韦作为标准品,以及在Vero细胞中的柯萨奇B4病毒,测试了该化合物在HEL细胞培养物中针对HSV-1(KOS),HSV-2(G)HSV-1 TK - KOS ACV r和VV的抗病毒作用利巴韦林和麦考酚酸作为标准品进行培养。发现R 2乙基取代的7个衍生物对测试的病毒有效。R 1 4-CF 3取代的7d,R 1 4-OCH 3取代的7 g和R 1 3-Cl取代的7 l显示出对HSV-1(KOS),HSV-2(G)HSV-1 TK - KOS ACV r和VV的活性。而只有R 1 4-Br取代的7n具有针对柯萨奇B4病毒的选择性活性。进行了7d7l的分子建模研究,以确定HSV-1糖蛋白B和D,HSV-2糖蛋白B结构的结合侧。

更新日期:2020-09-05
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