Dipartimento di Scienze Biomediche, Sezione di Microbiologia e Virologia, Università degli Studi di Cagliari, Cittadella Universitaria s.p.8, Km 0,700, 09042 Monserrato, Ca, Italy.
Dipartimento di Chimica e Farmacia, Università degli Studi di Sassari, Via Muroni 23/A, 07100 Sassari, Italy.
Eur J Med Chem. 2014 Sep 12;84:8-16. doi: 10.1016/j.ejmech.2014.07.011. Epub 2014 Jul 4.
Continuing our program of research concerning the antiviral activity of a wide series of new angular and linear azolo bicyclic and tricyclic derivatives, now we have simplified and modified the 4-chloro-2-(4-nitrophenyl)-3H-imidazo[4,5-g]quinoline 1, which previously resulted the most active derivative, through either the elimination of the central ring or the opening of the imidazole ring, obtaining various imidazopyridines and N-benzylidenequinolinamines respectively. Title compounds were tested in cell-based assays for cytotoxicity and antiviral activity against representatives of two DNA virus families as wells as against representatives of RNA virus families containing single-stranded, either positive-sense (ssRNA(+)) or negative-sense (ssRNA(-)), and double-stranded genomes (dsRNA). Some imidazo[4,5-b]pyridines emerged as new derivatives endowed with antiviral activity against Vaccinia Virus (VV) at concentrations ranging from 2 to 16 μM. In particular, compound 2b demonstrate to be about 10 times more potent than Cidofovir, used as reference drug. Similarly, the imidazo[4,5-c]pyridines and N-benzylidenequinolinamines derivatives resulted active against Bovine Viral Diarrhoea virus (BVDV), at concentrations ranging from 1.2 to 28 μM. Above all compounds 1, 3a and 3f showed an EC50 of the same order of magnitude of the reference drug, the 2'-C-methyl-guanosine. Moreover, several N-benzylidenequinolinamines showed an interesting activity against Respiratory Syncytial Virus (RSV) at concentrations between 12 and 26 μM.
延续我们对一系列新型角状和线状氮杂双环和三环衍生物的抗病毒活性的研究计划，现在我们简化并修饰了 4-氯-2-(4-硝基苯基)-3H-咪唑并[4,5-g]喹啉 1，该化合物之前是最具活性的衍生物，通过消除中环或打开咪唑环，分别得到各种咪唑并吡啶和 N-苄基亚基喹啉胺。标题化合物在细胞基础测定中进行了细胞毒性和抗病毒活性测试，针对两种 DNA 病毒家族以及含有单链、正链（ssRNA(+)）或负链（ssRNA(-)）和双链基因组（dsRNA）的 RNA 病毒家族的代表进行了测试。一些咪唑并[4,5-b]吡啶作为具有抗痘病毒（VV）活性的新型衍生物出现，其浓度范围为 2 至 16 μM。特别是化合物 2b 被证明比作为参考药物的西多福韦的效力高约 10 倍。同样，咪唑并[4,5-c]吡啶和 N-苄基亚基喹啉胺衍生物对牛病毒性腹泻病毒（BVDV）表现出活性，其浓度范围为 1.2 至 28 μM。在所有化合物中，1、3a 和 3f 的 EC50 与参考药物 2'-C-甲基鸟苷的相同数量级。此外，几种 N-苄基亚基喹啉胺在 12 至 26 μM 之间对呼吸道合胞病毒（RSV）表现出有趣的活性。
