Synthesis and evaluation of ent-Conduramine C-1 derivatives as α-glucosidase inhibitors via CSI-mediated amination reaction.

Concise synthesis of ent-conduramine C-1 and its derivatives has been achieved by using commercially available d-ribose. The key steps in the synthesis are regioselective and diastereoselective amination of polybenzyl ethers by chlorosulfonyl isocyanate (CSI), chelation-controlled carbonyl addition, and intramolecular olefin metathesis. All of the synthesized compounds were evaluated for inhibitory activity against α-glucosidase. The derivatives 18 (IC50 = 0.65 ± 0.03 mM) and 19 (IC50 = 0.26 ± 0.01 mM) were identified to be more potent than well-known α-glucosidase inhibitor acarbose (IC50 = 1.05 ± 0.17 mM) as a positive control.

Quantitative detection of telomerase activity by real-time TRAP assay in the body fluids of cancer patients.

Real-time TRAP assay was developed to improve the sensitivity and quantitative detection of telomerase activity in the body fluids of cancer patients. The sensitivity and clinical significance of the real-time TRAP assay was investigated. Real-time PCR protocol was modified by using ACX primer and SYBR green mixture from the process of TS primer extension. Real-time TRAP showed high correlation (r2=0.843, p=0.001) and sensitivity (25 times higher) compared to conventional TRAP. Of 164 samples, there were 8 positives in cytology (4.9%), 7 (4.3%) using the conventional TRAP, and 41 (25%) using real-time TRAP. In cytology positive samples, real-time TRAP showed a higher positivity than conventional TRAP (75% vs 63%) suggesting a higher sensitivity in the body fluids. There was a tendency towards a longer progression-free duration in telomerase negative patients than in positive patients, as determined by conventional and real-time TRAP. The diagnostic interval between the first positivity documentation and clinical progression was short in the order of real-time TRAP, conventional TRAP and cytology. In conclusion, real-time TRAP assay can detect telomerase activity at an earlier phase of cancer progression and can replace conventional TRAP assay for detecting the telomerase activity in body fluids.