Circadian and chemotherapy-related changes in urinary modified nucleosides excretion in patients with metastatic colorectal cancer

Urinary levels of modified nucleosides reflect nucleic acids turnover and can serve as non-invasive biomarkers for monitoring tumour circadian dynamics, and treatment responses in patients with metastatic colorectal cancer. In 39 patients, median overnight urinary excretion of LC-HRMS determinations of pseudouridine, was ~ tenfold as large as those of 1-methylguanosine, 1-methyladenosine, or 4-acetylcytidine, and ~ 100-fold as large as those of adenosine and cytidine. An increase in any nucleoside excretion after chemotherapy anticipated plasma carcinoembryonic antigen progression 1–2 months later and was associated with poor survival. Ten fractionated urines were collected over 2-days in 29 patients. The median value of the rhythm-adjusted mean of urinary nucleoside excretion varied from 64.3 for pseudouridine down to 0.61 for cytidine. The rhythm amplitudes relative to the 24-h mean of 6 nucleoside excretions were associated with rest duration, supporting a tight link between nucleosides turnover and the rest-activity rhythm. Moreover, the amplitude of the 1-methylguanosine rhythm was correlated with the rest-activity dichotomy index, a significant predictor of survival outcome in prior studies. In conclusion, urinary excretion dynamics of modified nucleosides appeared useful for the characterization of the circadian control of cellular proliferation and for tracking early responses to treatments in colorectal cancer patients

Breakthroughs in medicinal chemistry: New targets and mechanisms, new drugs, new hopes-6

Breakthroughs in Medicinal Chemistry: New Targets and Mechanisms, New Drugs, New Hopes is a series of Editorials that is published on a biannual basis by the Editorial Board of the Medicinal Chemistry section of the journal Molecules [...]

Association of a Love wave sensor to thin film molecularly imprinted polymers for nucleosides analogs detection

International audienceThe overall objective of this work is to develop and validate a quantitative, non-invasive therapeutic tool to detect selected urinary modified nucleosides as biomarkers of colorectal cancer chemotherapy and to monitor in fine the efficiency of the chemotherapy. Our methodology takes the advantage of high sensitivity of acoustic biosensor combined with high selectivity and robustness of thin molecularly imprinted polymer (MIP) film. In this paper we present a process based on a thin film of a MIP of adenosine 5'-monophosphate (AMP) coating on the sensor surface which is compatible with the acoustic wave propagation. Detection tests of AMP have been performed in aqueous media. The sensor response was recorded in terms of synchronous frequency and total insertion losses after both steps: extraction from, rebinding by the MIP layer. A frequency decrease of 6.875 Hz was recorded for 25μg/mL AMP concentration

Synthesis of L-cyclopentenyl nucleosides using ring-closing metathesis and palladium-mediated allylic alkylation methodologies

The enantiomeric synthesis of L-cyclopentenyl nucleosides is described. The key intermediate (+)-cyclopentenyl alcohol (8) was prepared from methyl-alpha-D-galactopyranoside 1 using a ring closing metathesis reaction. Transformation of the allylic alcohol 8 into the allylic acetate (9) or carbonate (10), allows their coupling with purine and pyrimidine bases under Pd(0)-catalyzed Tsuji-Trost allylic alkylation's to yield 12a-c. The Pd catalyzed reaction was found to require the use of AlEt3. (C) 2004 Elsevier Ltd. All rights reserved.</p

Study of copper(I) catalysts for the synthesis of carbanucleosides via azide-alkyne 1,3-dipolar cycloaddition

The activity of three copper(I)-based catalytic systems in the preparation of various 1,2,3 -triazolyl-carbanucleosides via the Huisgen azide-alkyne 1,3-dipolar cycloaddition is presented. The influence of the alkyne substituent, solvent, and heating mode were studied. The preparation of [1,2-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene]bromocopper [(IMes)CuBr] is discussed