Antitumor Agents. 5. Synthesis, structure−activity relationships, and biological evaluation of dimethyl-5H-pyridophenoxazin-5-ones, tetrahydro-5H-benzopyridophenoxazin-5-ones, and 5H-benzopyridophenoxazin-5-ones with potent antiproliferative activity.

New antiproliferative compounds, dimethyl-5H-pyrido[3,2-a]phenoxazin-5-ones (1−6), tetrahydro-5H-benzopyrido[2,3-j]phenoxazin-5-ones (7−9), and 5H-benzopyrido[3,2-a]phenoxazin-5-ones (10−12) were synthesized and evaluated against representative human neoplastic cell lines. Dimethyl derivatives 1−6 were more active against carcinoma than leukemia cell lines. The tetrahydrobenzo derivatives 7−9 were scarcely active, whereas the corresponding benzo derivatives 10−12 showed notable cytotoxicity against a majority of the tested cell lines. Molecular modeling studies indicated that the high potency of 10 and 11, the most cytotoxic compounds of the whole series, could be due to the position of the condensed benzene ring, which favors π−π stacking interactions with purine and pyrimidine bases in the DNA active site. Biological studies suggested that 10−12 have no effect on human topoisomerases I and II and that they induce arrest at the G2/M phase

Nutraceutical value and toxicological profile of selected red wines from Morocco

The polyphenolic composition, antioxidant properties and multielement profile of selected red wines from Morocco were evaluated. The polyphenolic contents resulted higher than those reported elsewhere for the same variety of wines; the highest quantity was found in Cabernet Sauvignon, followed by Merlot, and last by Syrah wine. All of the wines tested showed very similar anthocyanin and flavonol patterns: individual compound contents resulted generally higher in comparison to conventional wines. The content of trans-resveratrol was significantly higher than that of cis-resveratrol in all of the wine samples. Particularly, Merlot showed the highest concentration of trans-resveratrol while Syrah exhibited the highest levels of cis-resveratrol. Reducing capacity resulted higher than antiradical property for all of the wines. The metal concentrations were below the official limits. The elemental pattern of wines were very similar, excepted V, Mn, Fe, Cu, As and Mo, for which Syrah markedly differed from the other wine samples

Novel Anti-HIV agents targeted to the HIV-1 Reverse Transcriptase associated Ribonuclease H function: Quinolonyl Acid and 5,6-Dihidroxybenzopyranone derivatives

Background. The HIV-1 RT has two associated activities: i) the DNA polymerase activity (both RNA and DNA dependent) and ii) the ribonuclease H (RNase H) activity, that selectively degrades the RNA strand of the RNA/DNA hybrid formed during the reverse transcription process. The HIV-1 RT-associated RNase H function is one of the several steps of the HIV-1 life cycle that are potentially vulnerable to a specific inhibition. Several studies have demonstrated that the abolition of the HIV-1 RNase H function stops the virus replication. All RT inhibitors currently approved for the treatment of HIV infection inhibit the RT polymerase activity, while none of them block the RT associated RNase H activity. Until now, only a few compounds have been reported to inhibit the HIV-1 RNase H function. However, with very few exceptions, they are not truly selective for the HIV-1 RT-associated RNase H activity since most of them inhibit also the HIV-1 RT-associated RDDP activity or the RNase H from other organisms. Since several years we have been engaged in the design and synthesis of RNase H inhibitors. Methods. Recently, we have discovered a new class of RNase H selective inhibitors characterized by quinolonyl carboxylic acid and 5,6-dihydroxybenzopyranone scaffolds and tested them on the HIV-1 RT-associated RNase H function. Results. The preliminary data showed that newly synthesized compounds inhibited the HIV-1 RT-associated RNase H function in the low micromolar range. Conclusions. SAR analysis and mode of action of the inhibitors will be discussed