Synthesis of β-triphosphotriester pronucleotides

Dinucleoside phosphorochloridite were synthesized from phosphorus trichloride and three nucleoside analogues, 3-fluoro-2,3-dideoxythymidine (FLT), 2\u27,3\u27-dideoxy-5-fluoro-3\u27- thiacytidine (FTC), and 2\u27,3\u27-dideoxy-3\u27-thiacytidine (3TC), in a multistep synthesis. Polymerbound N-Boc p-acetoxybenzyl 5¢-O-2¢-deoxythymidine was reacted with dinucleoside phosphorochloridite in the presence of 2,6-lutidine, followed by the reaction with dodecyl alcohol and 5-(ethylthio)-1H-tetrazole, oxidation with tert-butyl hydroperoxide, and acidic cleavage, respectively, to afford the b-triphosphotriester derivatives containing three different nucleosides

Synthesis and antiproliferative activities of quebecol and its analogs

Simple and efficient synthesis of quebecol and a number of its analogs was accomplished in five steps. The synthesized compounds were evaluated for antiproliferative activities against human cervix adenocarcinoma (HeLa), human ovarian carcinoma (SK-OV-3), human colon carcinoma (HT-29), and human breast adenocarcinoma (MCF-7) cancer cell lines. Among all the compounds, 7c, 7d, 7f, and 8f exhibited antiproliferative activities against four tested cell lines with inhibition over 80% at 75 μM after 72 h, whereas, compound 7b and 7g were more selective towards MCF-7 cell line. The IC50 values for compounds 7c, 7d, and 7f were 85.1 μM, 78.7 μM, and 80.6 μM against MCF-7 cell line, respectively, showing slightly higher antiproliferative activtiy than the synthesized and isolated quebecol with an IC50 value of 104.2 μM against MCF-7. [Refer to PDF for graphical abstract

Synthesis of substituted 2,2' and 4,4'-bithiazoles in various solvents

498-499Some tetra substituted derivatives of 2,2' and 4,4' bithiazoles have been synthesized and characterized in various solvents

Cyclic Peptide–Selenium Nanoparticles as Drug Transporters

A cyclic peptide composed of five tryptophan, four arginine, and one cysteine [W₅R₄C] was synthesized. The peptide was evaluated for generating cyclic peptide-capped selenium nanoparticles (CP–SeNPs) in situ. A physical mixing of the cyclic peptide with SeO₃^–2 solution in water generated [W₅R₄C]–SeNPs via the combination of reducing and capping properties of amino acids in the peptide structure. Transmission electron microscopy (TEM) images showed that [W₅R₄C]–SeNPs were in the size range of 110–150 nm. Flow cytometry data revealed that a fluorescence-labeled phosphopeptide (F′-PEpYLGLD, where F′ = fluorescein) and an anticancer drug (F′-dasatinib) exhibited approximately 25- and 9-times higher cellular uptake in the presence of [W₅R₄C]–SeNPs than those of F′-PEpYLGLD and dasatinib alone in human leukemia (CCRF-CEM) cells after 2 h of incubation, respectively. Confocal microscopy also exhibited higher cellular delivery of F′-PEpYLGLD and F′-dasatinib in the presence of [W₅R₄C]–SeNPs compared to the parent fluorescence-labeled drug alone in human ovarian adenocarcinoma (SK-OV-3) cells after 2 h of incubation at 37 °C. The antiproliferative activities of several anticancer drugs doxorubicin, gemcitabine, clofarabine, etoposide, camptothecin, irinotecan, epirubicin, fludarabine, dasatinib, and paclitaxel were improved in the presence of [W₅R₄C]–SeNPs (50 μM) by 38%, 49%, 36%, 36%, 31%, 30%, 30%, 28%, 24%, and 17%, respectively, after 48 h incubation in SK-OV-3 cells. The results indicate that CP–SeNPs can be potentially used as nanosized delivery tools for negatively charged biomolecules and anticancer drugs