Synthesis and dengue inhibition potential of new uridine derivatives: The DENV 2 inhibitors.

IF 0.7 4区 医学 Q4 PHARMACOLOGY & PHARMACY Pakistan journal of pharmaceutical sciences Pub Date : 2024-07-01
Sangeeta Vani Alagasamy, Shivkanya Fuloria, Freddy Franklin, Chandramathi Samudi Raju, Dharshini Jagadeesan, Mohammad Auwal Sa'ad, Ravichandran Veerasamy, Vetriselvan Subramaniyan, Yuan Seng Wu, Sundram Karupiah, Neeraj Kumar Fuloria
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Abstract

Dengue is an important arboviral infection worldwide for which presently there is no specific medicine. Evidence suggests there are four serotypes of dengue virus (DENV1-4), of which DENV 2 is considered to cause the most sever dengue. Therefore, this study was aimed to develop the new uridine derivatives (NUDs) against dengue virus (DENV 2). In current study 2-(3,4-dihydroxy-5-(hydroxymethyl)-tetrahydrofuran-2-yl)-4-((substituted cyclohexa-2,5-dienylidene)methyl)-1,2,4-triazine-3,5(2H,4H)-dione (2a-f), were obtained via reaction of substituted uridine (1) and different aromatic aldehydes separately. Synthesized NUDs were further characterized using FTIR, 1H & 13C-NMR, mass and element analysis data. Characterized NUDs were assessed for their inhibition potential against DENV 2. Synthesized NUDs were also evaluated for their cytotoxicity towards Vero cells by MTT assay method. This investigation successfully synthesized NUDs 2a-f and reported their high inhibitory activity against DENV 2. The synthesized NUDs exhibited negligible cytotoxicity. High anti-viral activity against DENV 2 serotype and least/no cytotoxicity of NUDs suggests their importance in the treatment of dengue. Present study recommends that in future these NUDs must be investigated for their clinical importance to establish them as a choice for dengue treatment.

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新尿苷衍生物的合成和登革热抑制潜力:DENV 2 抑制剂。
登革热是全球范围内一种重要的虫媒病毒感染,目前尚无特效药物。有证据表明,登革热病毒有四种血清型(DENV1-4),其中 DENV 2 被认为是导致登革热最严重的病毒。因此,本研究旨在开发针对登革热病毒(DENV 2)的新尿苷衍生物(NUDs)。在本研究中,2-(3,4-二羟基-5-(羟甲基)-四氢呋喃-2-基)-4-((取代环己-2,5-二烯亚基)甲基)-1,2,4-三嗪-3,5(2H,4H)-二酮(2a-f)分别由取代尿苷(1)和不同的芳香醛反应得到。合成的 NUD 利用傅立叶变换红外光谱、1H 和 13C-NMR 以及质量和元素分析数据进行了进一步表征。评估了表征的 NUDs 对 DENV 2 的抑制潜力。还通过 MTT 检测法评估了合成的 NUD 对 Vero 细胞的细胞毒性。这项研究成功合成了 NUDs 2a-f,并报告了它们对 DENV 2 的高抑制活性。合成的 NUDs 的细胞毒性可忽略不计。NUDs 对 DENV 2 血清型具有很高的抗病毒活性,而且细胞毒性很小/没有,这表明它们在治疗登革热方面具有重要意义。本研究建议,今后必须对这些 NUDs 的临床重要性进行研究,以确定它们是治疗登革热的一种选择。
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来源期刊
CiteScore
1.40
自引率
12.50%
发文量
211
审稿时长
4.5 months
期刊介绍: Pakistan Journal of Pharmaceutical Sciences (PJPS) is a peer reviewed multi-disciplinary pharmaceutical sciences journal. The PJPS had its origin in 1988 from the Faculty of Pharmacy, University of Karachi as a biannual journal, frequency converted as quarterly in 2005, and now PJPS is being published as bi-monthly from January 2013. PJPS covers Biological, Pharmaceutical and Medicinal Research (Drug Delivery, Pharmacy Management, Molecular Biology, Biochemical, Pharmacology, Pharmacokinetics, Phytochemical, Bio-analytical, Therapeutics, Biotechnology and research on nano particles.
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