Synthesis of dioxane-based antiviral agents and evaluation of their biological activities as inhibitors of Sindbis virus replication

Abstract

The crystal structure of the Sindbis virus capsid protein contains one or two solvent-derived dioxane molecules in the hydrophobic binding pocket. A bisdioxane antiviral agent was designed by linking the two dioxane molecules with a three-carbon chain having R,R connecting stereochemistry, and a stereospecific synthesis was performed. This resulted in an effective antiviral agent that inhibited Sindbis virus replication with an EC50 of 14μM. The synthesis proceeded through an intermediate (R)-2-hydroxymethyl-[1,4]dioxane, which unexpectedly proved to be a more effecting antiviral agent than the target compound, as evidenced by its EC50 of 3.4μM as an inhibitor of Sindbis virus replication. Both compounds were not cytotoxic in uninfected BHK cells at concentrations of 1 mM.

Synthesis, antimicrobial and antiviral evaluation of substituted imidazole derivatives

“…In continuation with our research program concerning the synthesis and antimicrobial evaluation of medicinally important compounds [25][26][27][28][29][30][31][32][33], in the present study we have synthesized 2-(substituted phenyl)-1H-imidazoles (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12). Further recent literature revealed that N 1 -substitution of imidazoles improves the antibacterial activity [34].…”

“…Infection can result in fever, rash, arthralgia or arthritis, lassitude, headache, and myalgia. The prototypic alphavirus is Sindbis virus (SINV), which is transmitted to humans through mosquito bites [8]. Respiratory syncytial virus (RSV), a paramyxovirus, is an important cause of respiratory tract infection in infants, young children and adults [9].…”

Ninhydrin in synthesis of heterocyclic compounds

“…[508][509][510][511] Numerous reactions between electron-rich, more-or less-polar enamines, such as 464, with ninhydrin 1 was reported by Schank and co-workers, and various new derivatives were formed (Scheme 151). The reaction products of ninhydrin and phenyl-and p-chlorophenyl-alanine were identified as racemic indeno-oxazinones 478 (Figure 4).…”

Unusual Totally Selective Cyclodimerization of Epoxides: Synthesis of a Pair of Diastereoisomers of Enantiopure 2,5‐Disubstituted‐1,4‐Dioxanes with C2 Symmetry

“…Hence, they are used in the manufacture of polycarbonates with photoreceptor properties, [2] cosmetic products, [3] flame retardant additives for flammable plastics, [4] insecticides, acaricides and ectoparasiticides, [5] or germicides and fungicides. [6] In addition, some of these also offer biomedical applications [7] such as, for example, inhibitors of epidermal growth factor receptor tyrosine kinase, [8] or as antiobesity agents. [9] In spite of the significant applications of 1,4-dioxanes, it is surprising that very few methods for the synthesis of racemic 1,4-dioxanes have been reported in the literature.…”