Synthesis and Antiviral Activity of Novel Acyclic Nucleoside Analogues of 5-(1-Azido-2-haloethyl)uracils

We present the discovery of a novel category of 5-substituted acyclic pyrimidine nucleosides as potent antiviral agents. A series of 1-[(2-hydroxyethoxy)methyl] (5−7), 1-[(2-hydroxy-1-(hydroxymethyl)ethoxy)methyl] (8−10), and 1-[4-hydroxy-3-(hydroxymethyl)-1-butyl] (11−13) derivatives of 5-(1-azido-2-haloethyl)uracil were synthesized and evaluated for their biological activity in cell culture. 1-[4-Hydroxy-3-(hydroxymethyl)-1-butyl]-5-(1-azido-2-chloroethyl)uracil (12) was the most effective antiviral agent in the in vitro assays against DHBV (EC50 = 0.31−1.55 μM) and HCMV (EC50 = 3.1 μM). None of the compounds investigated showed any detectable toxicity to several stationary and proliferating host cells

Table_2_Unveiling the distribution of free and bound phenolic acids, flavonoids, anthocyanins, and proanthocyanidins in pigmented and non-pigmented rice genotypes.docx

The total phenolic content, phenolic acid profile, anthocyanins, proanthocyanidins, flavonoids, and antioxidant capacity of the whole-grain and bran portion of sixteen distinct rice genotypes that correspond to three distinct pericarp bran colors—black, red, and non-pigmented (NP)—were examined. Ten free and bound phenolic acids, as well as two flavonoids, were analyzed using HPLC-PDA. The flavonoids included kaempferol and catechin hydrate, and the free phenolic acids included gallic acid, 2,5-dihydroxybenzoic acid, vanillic acid, syringic acid, p-coumaric acid, chlorogenic acid, trans-cinnamic acid, trans-ferulic acid, p-coumaric acid, and sinapic acid. Trans-ferulic acid (207.39 mg/kg), p-hydroxybenzoic acid (94.36 mg/kg), and p-coumaric acid (59.75 mg/kg) were the principal bound phenolic acids in pigmented rice genotypes, whereas in NP genotypes they were trans-ferulic acid (95.61 mg/kg) and p-hydroxybenzoic acid (58.32 mg/kg). The main free phenolic acid was syringic acid (120.43 mg/kg) in all genotypes. 2,5-dihydroxybenzoic acid was also detected in NP genotypes, mainly in the bound form (4.88 mg/kg). NP genotypes Basmati 386 and Punjab Basmati 7 also displayed high content of bran flavonoids (1001 and 1028 mg CE/100 g). The bound form of phenolics had significant DPPH and ABTS + activity. This study found wide diversity in the phenolic acid profile, total phenolic constituents, and antioxidant activity in the bran and whole grain of pigmented and NP rice. The individual phenolic acids in free and bound forms in different fractions of the grain were found to exert their antioxidant activity differently. The results obtained will provide new opportunities to improve the nutritional quality of rice with enhanced levels of phytochemicals in the ongoing breeding programs. Black rice bran contains a high level of phytochemicals and thus has a potent pharmaceutical role. This information would enhance the use of whole-grain and bran of pigmented rice in food product development by food technologists. Further studies may be focused on clinical trials with respect to cancer and diabetes.</p

Table_1_Unveiling the distribution of free and bound phenolic acids, flavonoids, anthocyanins, and proanthocyanidins in pigmented and non-pigmented rice genotypes.docx

The total phenolic content, phenolic acid profile, anthocyanins, proanthocyanidins, flavonoids, and antioxidant capacity of the whole-grain and bran portion of sixteen distinct rice genotypes that correspond to three distinct pericarp bran colors—black, red, and non-pigmented (NP)—were examined. Ten free and bound phenolic acids, as well as two flavonoids, were analyzed using HPLC-PDA. The flavonoids included kaempferol and catechin hydrate, and the free phenolic acids included gallic acid, 2,5-dihydroxybenzoic acid, vanillic acid, syringic acid, p-coumaric acid, chlorogenic acid, trans-cinnamic acid, trans-ferulic acid, p-coumaric acid, and sinapic acid. Trans-ferulic acid (207.39 mg/kg), p-hydroxybenzoic acid (94.36 mg/kg), and p-coumaric acid (59.75 mg/kg) were the principal bound phenolic acids in pigmented rice genotypes, whereas in NP genotypes they were trans-ferulic acid (95.61 mg/kg) and p-hydroxybenzoic acid (58.32 mg/kg). The main free phenolic acid was syringic acid (120.43 mg/kg) in all genotypes. 2,5-dihydroxybenzoic acid was also detected in NP genotypes, mainly in the bound form (4.88 mg/kg). NP genotypes Basmati 386 and Punjab Basmati 7 also displayed high content of bran flavonoids (1001 and 1028 mg CE/100 g). The bound form of phenolics had significant DPPH and ABTS + activity. This study found wide diversity in the phenolic acid profile, total phenolic constituents, and antioxidant activity in the bran and whole grain of pigmented and NP rice. The individual phenolic acids in free and bound forms in different fractions of the grain were found to exert their antioxidant activity differently. The results obtained will provide new opportunities to improve the nutritional quality of rice with enhanced levels of phytochemicals in the ongoing breeding programs. Black rice bran contains a high level of phytochemicals and thus has a potent pharmaceutical role. This information would enhance the use of whole-grain and bran of pigmented rice in food product development by food technologists. Further studies may be focused on clinical trials with respect to cancer and diabetes.</p

Number of different quality types in each grain length class based on combinations of the current tools for measuring quality: grain length (blue), shape, amylose content (red), gelatinisation temperature (green), and the presence of aroma.

<p>Number of different quality types in each grain length class based on combinations of the current tools for measuring quality: grain length (blue), shape, amylose content (red), gelatinisation temperature (green), and the presence of aroma.</p

Grain quality traits in non-Asian rice-growing countries.

<p>Some countries do not measure all traits.</p

Regional variation in amylose content of the three most popular varieties in the countries, states, and provinces of Asia.

<p>In some regions, two types of amylose class are preferred. Additional information for other regions can be found in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0085106#pone-0085106-t002" target="_blank">Table 2</a>. Data were obtained from INQR representatives from each region.</p

Consumer preferences for texture based on gel consistency values.

<p>In many countries and regions, gel consistency is not measured (grey). Additional information for the other regions can be found in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0085106#pone-0085106-t002" target="_blank">Table 2</a>. Data obtained from INQR representatives from each region.</p

Regional variation in gelatinisation temperature of the three most popular varieties in the countries, states, and provinces of Asia.

<p>In some regions, two classes are preferred. Additional information for other regions can be found in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0085106#pone-0085106-t002" target="_blank">Table 2</a>. Data were obtained from INQR representatives from each region.</p

Principal Components Analysis of the volatile metabolomic signature of the traditional indica varieties from the Greater Mekong Subregion (GMS), basmati varieties from South Asia, and the sadri varieties from Iran.

<p>PC1 explains 27% and PC2 explains 21% of variation.</p

Regional variation in rice length and shape (length/width) of the three most popular varieties in the countries, states, and provinces of Asia.

<p>In some regions, more than one type of grains lengths and shapes are preferred. Colours represent length, and lines represent the shape. Additional information for other regions can be found in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0085106#pone-0085106-t002" target="_blank">Table 2</a>. Data were obtained from INQR representatives from each region.</p