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几种三氮烯衍生物抗登革病毒的潜力。

Potential of several triazene derivatives against DENGUE viruses.

作者信息

Sokhna Seynabou, Mérindol Natacha, Presset Marc, Seck Insa, Girard Marie-Pierre, Ka Seydou, Ndoye Samba Fama, Ba Aïcha Lalla, Samb Issa, Berthoux Lionel, Le Gall Erwan, Desgagné-Penix Isabel, Seck Matar

机构信息

Laboratoire de Chimie Organique et Thérapeutique, Faculté de Médecine, de Pharmacie et d'Odontologie de l'Université Cheikh Anta Diop de Dakar, BP 5005 Dakar-Fann, Sénégal; UMR 7182, ICMPE, Institut de Chimie et des Matériaux Paris Est, Thiais, France; Equipe de recherche chimie organique et thérapeutique (ECOT) de l'Université Alioune Diop de Bambey. BP 30 Région de Diourbel, Sénégal.

Département de chimie, biochimie et physique, UQTR, Trois-Rivières, QC, Canada.

出版信息

Bioorg Med Chem Lett. 2024 Mar 15;101:129646. doi: 10.1016/j.bmcl.2024.129646. Epub 2024 Feb 6.

Abstract

Dengue fever is an infectious disease caused by the dengue virus (DENV), an RNA Flavivirus transmitted by the mosquitoes Aedes aegypti and Aedes albopictus widespread in tropical, subtropical and also temperate regions. Symptoms range from a simple cold to a severe, life-threatening haemorrhagic fever. According to the WHO, it affects around 390 million people per year. No antiviral treatment for DENV is available, and the Dengvaxia vaccine is only intended for people over 9 years of age who have contracted dengue one time in the past, and shows serotype-specific effectiveness. There is therefore a crying need to discover new molecules with antiviral power against flaviviruses. The present study was carried out to evaluate the anti-DENV activities and cytotoxicity of triazenes obtained by diazocopulation. Some triazenes were highly cytotoxic (16, and 25) to hepatocarcinoma Huh7 cells, whereas others displayed strong anti-DENV potential. The antiviral activity ranged from EC = 7.82 µM to 48.12 µM in cellulo, with a selectivity index (CC/EC) greater than 9 for two of the compounds (10, and 20). In conclusion, these new triazenes could serve as a lead to develop and optimize drugs against DENV.

摘要

登革热是一种由登革病毒(DENV)引起的传染病,DENV是一种RNA黄病毒,由埃及伊蚊和白纹伊蚊传播,在热带、亚热带甚至温带地区广泛存在。症状从普通感冒到严重的、危及生命的出血热不等。据世界卫生组织称,每年约有3.9亿人受到影响。目前尚无针对DENV的抗病毒治疗方法,登革热疫苗仅适用于9岁以上且过去曾感染过一次登革热的人群,且显示出血清型特异性有效性。因此,迫切需要发现具有抗黄病毒抗病毒能力的新分子。本研究旨在评估通过重氮偶合获得的三氮烯的抗DENV活性和细胞毒性。一些三氮烯对肝癌Huh7细胞具有高度细胞毒性(16和25),而其他三氮烯则显示出强大的抗DENV潜力。在细胞内,抗病毒活性范围为EC = 7.82 µM至48.12 µM,其中两种化合物(10和20)的选择性指数(CC/EC)大于9。总之,这些新的三氮烯可作为开发和优化抗DENV药物的先导。

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