Radiolabeling and in vitro evaluation of a new 5-fluorouracil derivative with cell culture studies.

The clinical impact and accessibility of 99m Tc tracers for cancer diagnosis would be greatly enhanced by the availability of a new, simple, and easy labeling process and radiopharmaceuticals. 5-Fluorouracil is an antitumor drug, which has played an important role for the treatment of breast carcinoma. In the present study, a new derivative of 5-Fluorouracil was synthesized as (1-[{1'-(1''-deoxy-2'',3'':4'',5''-di-O-isopropylidene-ß-D-fructopyranose-1''-yl)-1'H-1',2', 3'-triazol-4'-yl}methyl]-5-fluorouracil) (E) and radiolabeled with 99m Tc. It was analyzed by radio thin layer chromatography for quality control and stability. The radiolabeled complex was subjected to in vitro cell-binding studies to determine healthy and cancer cell affinity using HaCaT and MCF-7 cells, respectively. In addition, in vitro cytotoxicity studies of compound E were performed with HaCaT and MCF-5 cells. The radiochemical purity of the [99m Tc]TcE was found to be higher than 90% at room temperature up to 6 hours. The radiolabeled complex showed higher specific binding to MCF-7 cells than HaCaT cells. IC50 values of E were found 31.5 ± 3.4 µM and 20.7 ± 2.77 µM for MCF-7 and HaCaT cells, respectively. The results demonstrated the potential of a new radiolabeled E with 99m Tc has selective for breast cancer cells.

Recent applications of chiral calixarenes in asymmetric catalysis.

The use of calixarenes in asymmetric catalysis is receiving increasing attention due to their tunable three-dimensional molecular platforms along with their easy syntheses and versatile modification at the upper and lower rims. This review summarizes the recent progress of synthesis and use of chiral calixarenes in asymmetric syntheses which emerged later than 2010.

Formulation, characterization, cytotoxicity and Salmonella/microsome mutagenicity (Ames) studies of a novel 5-fluorouracil derivative.

5-Fluorouracil is one of the first line drugs for the systemic therapy of solid tumors like breast, colorectal, oesophageal, stomach, pancreatic, head and neck. It could be shown that sugars can improve the absorption across cell membranes and can help to bypass some pharmacokinetic problems. Carbohydrates as most common organic molecules are an important issue of plant and animal metabolisms. They are non toxic and have important duties in the body like participating in DNA and RNA synthesis and being responsible for energy production. In addition, they have many hydroxyl, aldehyde and ketone groups that attract attention for synthesis as a potential drug derivative. 1,2,3,-Triazole compounds have also important role in heterocyclic chemistry because of their pharmaceutical properties and their high reactivity, which could be used as a building block for complex chemical compounds. In this study, following the "Click Reaction" of 5-FU and tetra-O-acetylglycose the 5-fluorouracil derivative 1-[{1'-(2″,3″,4″,6″-tetra-O-acetyl-ß-d-glycopyronosyl)-1'H-1',2',3'-triazole-4'-yl} methyl]5-fluorouracil was synthesized. Following, a micellar formulation of 5-Fluorouracil derivative was prepared and characterized in terms of particle size, polydispersity index, zeta potential, refractive index and pH. Furthermore, the cytotoxicity and mutagenicity of the 5-fluorouracil derivative was investigated using an in vitro cell culture model and the AMES test. According to the results of this study, the novel 5-fluorouracil derivative could be a drug candidate for the therapy of cancer and needs further in vivo investigations.

Enantioselective recognition of carboxylic acids by novel fluorescent triazine-based thiazoles.

Hydrogen bonding and π-π interactions take special part in the enantioselectivity task. In this regard, because of having both hydrogen acceptor and hydrogen donor groups, melamine derivatives become more of an issue for enantioselectivity. In the light of such information, triazine-based chiral, fluorescence active novel thiazole derivatives L1 and L2 were designed and synthesized from (S)-(-)-2-amino-1-butanol and (1S,2R)-(+)-2-amino-1,2-diphenylethanol. The structural establishment of these compounds was made by spectroscopic methods such as FTIR, 1 H, and 13 C NMR. While the solution of these compounds in DMSO did not show any fluorescence emission, it was observed that the emission increased 44-fold for L1 and 55-fold for L2 in 95% water, similar to the aggregation-induced emission (AIE) characterized compounds. In this regard, enantioselective capabilities of these compounds against carboxylic acids were tested, and in experiments carried out at a ratio of 40/60 DMSO/H2 O, it was determined that R-2ClMA increased the fluorescence emission of L1 chiral receptor by 2.59 times compared to S-isomer.

Syntheses of 1,2,3-triazole-bridged pyranose sugars with purine and pyrimidine nucleobases and evaluation of their anticancer potential.

With the aim to create a library of compounds with potential bioactivities by combining special characteristics of two important groups such as nucleobases and carbohydrates, twenty 1,4-disubstituted-triazole nucleosides were synthesized in good yields (80-94%) using the copper catalyzed 'Click' reaction between azido-modified pento- or hexopyranoses and alkyne-bearing pyrimidine or purine nucleobases. Structural elucidation was made with the assistance of spectroscopic techniques such as FTIR, 1D-, 2D-NMR, and ESI-TOFMS. All the synthesized triazole nucleosides were evaluated for their cytotoxic activity against three human cancer cell lines (MDA-MB-231, Hep3B, PC-3) by using the MTT assay. Particularly, compounds 3a and 1b were identified as potential hits against Hep3B cell.