Synthesis, anticancer and antiviral activities of novel thiopyrano[2,3-<i>d</i>]thiazole-6-carbaldehydes

<p>Novel rel-(6R,7R)-2-oxo-7-phenyl-3,5,6,7-tetrahydro-2H-thiopyrano[2,3-d]thiazole-6-carbaldehydes were synthesized via regio- and diastereoselective hetero-Diels-Alder reaction of 5-arylidene-4-thioxo-2-thiazolidinones with acrolein. The synthesized compounds were evaluated for anticancer and antiviral activities by the National Institutes of Health (NIH) following US NCI and AACF protocols. Anticancer activity screening on NCI60 cell lines allowed identification of 7-phenyl-2-oxo-7-phenyl-3,5,6,7-tetrahydro-2H-thiopyrano[2,3-d]thiazole-6-carbaldehyde <b>3a</b> with the highest level of antimitotic activity against leukemia with mean GI₅₀/TGI values 1.26/25.22 μM. The screening of antiviral activity lead to identification of 7-(4-methoxyphenyl)-2-oxo-3,5,6,7-tetrahydro-2H-thiopyrano[2,3-d]thiazole-6-carbaldehyde <b>3b</b> with a promising influence on EBV virus (EC₅₀ = 0.07 μM, SI = 3279) and moderate effect on Herpes simplex virus type 1 and Varicella zoster virus and 7-[4-(benzyloxy)phenyl]-2-oxo-3,5,6,7-tetrahydro-2H-thiopyrano[2,3-d][1,3]thiazole-6-carbaldehyde <b>3e</b> with a promising influence on Hepatitis C virus (EC₅₀ = 12.6 μM, SI = 43.1).</p

A <i>Helicobacter pylori-</i>associated insulin resistance in asymptomatic sedentary young men does not correlate with inflammatory markers and urine levels of 8-iso-PGF₂-α or 1,4-dihydroxynonane mercapturic acid

<p>A potential contribution of <i>H. pylori</i> contamination to low-grade inflammation, oxidative stress (OS) and insulin resistance as well as correlations between these parameters in asymptomatic sedentary males was analysed. We enrolled 30 apparently healthy asymptomatic young subjects (18 <i>H. pylori</i> negative and 12 positive) and measured whole blood glucose, glycated haemoglobin, insulin, C-peptide, cortisol, aldosterone, testosterone, thyroid stimulating hormone, C-reactive protein, interleukins 6 and 10, TNF-alpha and comet assay. As markers of OS, we used urine levels of iso-PGF₂-α and 1,4-dihydroxynonane mercapturic acid (DHN-MA). Twofold elevation of fasting insulin level and HOMA index in <i>H. pylori</i>–positive subjects (<i>p</i> < .05) was shown. Inflammatory parameters and monocyte DNA damage, urine levels of DHN-MA and iso-PGF2-α did not show significant differences between the groups. The early stage of <i>H. pylori</i>-triggered metabolic derangements in sedentary subjects include development of insulin resistance in <i>H. pylori</i>-positive subjects; however, there is no evidence of systemic inflammatory and OS-related changes.</p