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| http://dx.doi.org/10.1042/bj1010039c | DOI Listing |
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Rational design, synthesis, biological evaluation, molecular docking, and molecular dynamics of substituted uracil derivatives as potent anti-cancer agents.
Bioorg Chem
January 2025
Department of Photochemistry (Synthetic Unit), Chemical Industries Research Institute, National Research Centre, Cairo 12622, Egypt. Electronic address:
An efficient synthesis of a series of uracil analogous was performed to obtain new potential anticancer agents. The cytotoxic effect of the synthesized derivatives was assessed in vitro against three cancer cell lines, namely hepatic cancer (HepG-2), colon cancer (HCT-116), and breast cancer (MCF-7). Among the tested compounds, 5, 11 and 15 stood as potent uracil derivatives with pan cytotoxicity against the 3 cell lines out-performing the reference compound 5-FU.
View Article and Find Full Text PDFPhase I study of neoadjuvant chemoradiotherapy with S-1 for clinically resectable type 4 or large type 3 gastric cancer in elderly patients aged 75 years and older (OGSG1303).
Med Oncol
December 2024
Department of Surgery, Faculty of Medicine, Kindai University, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka, 589-8511, Japan.
Purpose The prognosis for type 4 and large type 3 gastric cancer (GC) is extremely poor, especially in elderly patients (≥ 75 years). To improve the prognosis of these types of GC, we performed a phase I study to determine the recommended dose (RD) of S-1 combined with neoadjuvant radiotherapy. Methods Patients with clinically resectable type 4 and large type 3 GC were enrolled to successive cohorts in a conventional 3 + 3 design.
View Article and Find Full Text PDFA simple method for estimating time-irreversible nucleotide substitution rates in the SARS-CoV-2 genome.
NAR Genom Bioinform
March 2024
Department of Natural Sciences, Faculty of Arts and Sciences, 1-23-1 Komazawa, Setagaya-ku, Tokyo 154-8525, Japan.
SARS-CoV-2 is the cause of the current worldwide pandemic of severe acute respiratory syndrome. The change of nucleotide composition of the SARS-CoV-2 genome is crucial for understanding the spread and transmission dynamics of the virus because viral nucleotide sequences are essential in identifying viral strains. Recent studies have shown that cytosine (C) to uracil (U) substitutions are overrepresented in SARS-CoV-2 genome sequences.
View Article and Find Full Text PDFOne-Step Regioselective Synthesis of N-1-Substituted Dihydrouracils: A Motif of Growing Popularity in the Targeted Protein Degradation Field.
J Org Chem
December 2024
Medicinal Chemistry, Oncology R&D, AstraZeneca, The Discovery Centre, 1 Francis Crick Avenue, Cambridge CB2 0AA, United Kingdom.
The increasing popularity of the dihydrouracil motif in cereblon (CRBN) recruiting proteolysis-targeting chimeras (PROTACs) has necessitated the development of a facile, cost-effective, and high-yielding method for its introduction into molecules. To that end, we disclose herein an N-1 selective Pd-catalyzed cross-coupling of dihydrouracil with aryl electrophiles to provide access to medicinally relevant scaffolds in a single step. This approach exhibits excellent functional group tolerance and broad applicability to an abundance of (hetero)aryl halides and phenol derivatives and utilizes readily available catalyst/ligand systems.
View Article and Find Full Text PDFInduction chemotherapy for locally advanced nasopharyngeal carcinoma: Efficacy and safety of the TPC regimen compared to GP and TPF.
Oral Oncol
January 2025
Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi 530021, China; Department of Oncology, Wuming Hospital of Guangxi Medical University, Nanning, Guangxi 530199, China. Electronic address:
Background And Objectives: Gemcitabine plus cisplatin (GP) and docetaxel plus cisplatin plus fluorouracil (TPF) are induction chemotherapy (IC) regimens for locally advanced nasopharyngeal carcinoma (LA-NPC). The oral convenience of capecitabine presents its potential as a fluorouracil substitute in the TPF regimen, which has yet to be thoroughly investigated. This study aims to compare the efficacy and safety of the docetaxel, cisplatin, and capecitabine (TPC) with GP and TPF in LA-NPC.
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