Antiviral Effects of Novel 2-Benzoxyl-Phenylpyridine Derivatives

Abstract

Coxsackievirus B3 (CVB3) is the most common cause of acute and chronic viral myocarditis, primarily in children, while human adenovirus infections represent a significant cause of morbidity and mortality worldwide, in people of all ages. A series of novel 2-benzoxyl-phenylpyridine derivatives were evaluated for their potential antiviral activities against CVB3 and adenovirus type 7 (ADV7). Preliminary assays indicated that some of these compounds exhibited excellent antiviral effects on both CVB3 and ADV7 viruses; they could effectively inhibit virus-induced cytopathic effects, reduce viral progeny yields, and had similar or superior antiviral activities compared with the control drug, ribavirin. Further, these compounds targeted the early stages of CVB3 replication in cells, including viral RNA replication and protein synthesis, rather than inactivating the virus directly, inhibiting virus adsorption/entry, or affecting viral release from cells. Our data demonstrate that the tested 2-benzoxyl-phenylpyridine derivatives are effective inhibitors of CVB3 and ADV7, raising the possibility that these compounds might be feasible candidates for anti-viral agents.

Serinol-Based Benzoic Acid Esters as New Scaffolds for the Development of Adenovirus Infection Inhibitors: Design, Synthesis, and In Vitro Biological Evaluation

“…47,48 To the best of our knowledge, no symmetric compounds have been described as potential anti-HAdV agents. (iii) The functionalization: The serinol scaffold allowed us to develop new molecules keeping many important features present in the reported anti-HAdV agents mentioned above, mainly urea 32,34,38 and ester functions, 37 that have been identified as important for the antiviral activity (Figure 1). In our general backbone, the urea function was introduced at the nitrogen (this moiety could be considered an acyclic modification of the nitrogen base present in some anti-HAdV agents) (1, 3), while aromatic esters at the hydroxyls as an isosteric modification with respect to the aromatic amide function, which is present in niclosamide (5) and its derivatives, and also because of their presence in effective anti-HAdV agents (6).…”

“…(ii) The question of the symmetry: In the field of the development of different scaffolds with antiviral activities, different types of symmetric compounds have been described, such as novel symmetrical phenylenediamines targeting the viral NS3 helicase being potential anti-HCV agents, symmetrically disposed stilbenes as potent inhibitors of NS5A, and complex homodimeric structures with large molecular weights (daclastavir and other related symmetric compounds). , To the best of our knowledge, no symmetric compounds have been described as potential anti-HAdV agents. (iii) The functionalization: The serinol scaffold allowed us to develop new molecules keeping many important features present in the reported anti-HAdV agents mentioned above, mainly urea ,, and ester functions, that have been identified as important for the antiviral activity (Figure ). In our general backbone, the urea function was introduced at the nitrogen (this moiety could be considered an acyclic modification of the nitrogen base present in some anti-HAdV agents) ( 1 , 3 ), while aromatic esters at the hydroxyls as an isosteric modification with respect to the aromatic amide function, which is present in niclosamide ( 5 ) and its derivatives, and also because of their presence in effective anti-HAdV agents ( 6 ).…”

“…35,36 Benzoic acid esters were also developed as potential antiviral agents against HAdV 7 (6, Figure 1). 37 Our previous research was focused on the preparation of new piperazine-derived ureas/thioureas with inhibitory activity against HAdV type 5 (7, Figure 1). Optimized compounds blocked HAdV infection at nanomolar or low micromolar ranges, showing low cytotoxicity and acting in several phases of its life cycle.…”

“… , Benzoic acid esters were also developed as potential antiviral agents against HAdV 7 ( 6 , Figure ). Our previous research was focused on the preparation of new piperazine-derived ureas/thioureas with inhibitory activity against HAdV type 5 ( 7 , Figure ). Optimized compounds blocked HAdV infection at nanomolar or low micromolar ranges, showing low cytotoxicity and acting in several phases of its life cycle. − On the basis of our previous work and experience in the synthesis of new small libraries of compounds with other potential biological activity , and focused on searching novel scaffolds for the preparation of potential anti-HAdV agents, the major aim of this report was to present the design, synthesis, and in vitro biological evaluation of a small library (38 compounds) of different serinol derivatives.…”

Syntheses, Characterizations, and Inhibition Activities Against Coxsackievirus B3 of Iodobenzoic Hydrazide Functionalized Hexamolybdates

“…Coxsackievirus B3 (CVB3), as one kind of non-enveloped and single-stranded (+) RNA virus ( Rotbart, 2002 ), can cause many diseases, including aseptic meningitis, viral myocarditis, encephalitis, respiratory infection, hepatitis, pancreatitis, acute episodes of the hand and foot, and mouth disease of children ( Bryant et al, 2004 ). To date, some compounds have been reported to demonstrate inhibitory activities against CVB3 ( Kim et al, 2012 ; Wei et al, 2020 ). However, none of them have received final market approval owing to their low inhibitory activities and adverse effects ( Fechner et al, 2011 ).…”