A small library of 30 dihydropyrimidines was synthesized and evaluated for their in vitro antitubercular activity against Mycobacterium tuberculosis H(37)Rv. Two compounds, ethyl 4-[3-(4-fluorophenyl)-1-phenyl-1H-pyrazol-4-yl]-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5 carboxylate 4a and ethyl 4-[3-(4-nitrophenyl)-1-phenyl-1H-pyrazol-4-yl]-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate 4d were found to be the most active compounds in vitro with MIC of 0.02 μg/mL against MTB and were more potent than isoniazid.
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http://dx.doi.org/10.1016/j.bmcl.2010.08.046 | DOI Listing |
Eur J Pharmacol
January 2025
School of Biotechnology, KIIT Deemed to be University, Bhubaneswar - 751024, Odisha, India. Electronic address:
Colorectal cancer (CRC) remains a significant global health challenge, demanding continuous advancements in treatment strategies. This review explores the complexities of targeting colorectal cancer stem cells (CSCs) and the mechanisms contributing to resistance to 5-fluorouracil (5-FU). The efficacy of 5-FU is enhanced by combination therapies such as FOLFOXIRI and targeted treatments like bevacizumab, cetuximab, and panitumumab, particularly in KRAS wild-type tumors, despite associated toxicity.
View Article and Find Full Text PDFJ Adv Res
January 2025
Pharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing, China; Joint Laboratory for Research & Treatment of Spinal Cord Injury in Spinal Deformity, Capital Medical University, Beijing, China. Electronic address:
Introduction: Dihydropyrimidine dehydrogenase (DPD) is a major determinant of cancer 5-fluorouracyl (5-FU) resistance via its direct degradation. However, the mechanisms of tumoral DPD upregulation have not been fully understood.
Objectives: This study aimed to explore the role of S1PR2 in the regulation of tumoral DPD expression, identifying S1PR2 as the potential target for reversing 5-FU resistance.
Curr Pharm Des
January 2025
Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt.
The pyrimidine nucleus is a fundamental component of human DNA and RNA, as well as the backbone of many therapeutic agents. Its significance in medicinal chemistry is well-established, with pyrimidine derivatives receiving considerable attention due to their potent anticancer properties across various cancer cell lines. Numerous derivatives have been synthesized, drawing structural inspiration from known anticancer agents like dihydropyrimidine compounds, which include the active cores of drugs such as 5-fluorouracil and monastrol, both of which have demonstrated strong anticancer efficacy.
View Article and Find Full Text PDFCurr Top Med Chem
January 2025
Department of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS Academy of Higher Education & Research (JSS AHER), Mysuru, Karnataka, India.
Background: Several chemical studies described the physiological efficacy of 1,4- dihydropyridines (DHPs). DHPs bind to specific sites on the α1 subunit of L-type calcium channels, where they demonstrate a more pronounced inhibition of Ca2+ influx in vascular smooth muscle compared to myocardial tissue. This selective inhibition is the basis for their preferential vasodilatory action on peripheral and coronary arteries, a characteristic that underlies their therapeutic utility in managing hypertension and angina.
View Article and Find Full Text PDFJ Chromatogr A
January 2025
Department of Medicinal and Applied Chemistry, Kaohsiung Medical University (KMU), Kaohsiung City-807, Taiwan; Research Center for Precision Environmental Medicine, College of Medicine, Kaohsiung Medical University (KMU), Kaohsiung City-807, Taiwan; PhD Program in Environmental and Occupational Medicine, College of Medicine, Kaohsiung Medical University (KMU), Kaohsiung City-807, Taiwan; Department of Medical Research, Kaohsiung Medical University Hospital (KMUH), Kaohsiung Medical University, Kaohsiung, City-807, Taiwan; Department of Chemistry, National Sun Yat-sen University (NSYSU), Kaohsiung City, 804, Taiwan. Electronic address:
Patients with dihydropyrimidine dehydrogenase (DPD) deficiency in peripheral mononuclear cells are at higher risk of severe toxicity due to the improper dose of fluorouracil-based chemotherapy drugs, which has become an essential aspect for consideration in clinical studies. 5-fluorouracil (5-FU) is a first-line and second-line chemotherapy drug in adjuvant, neoadjuvant, or palliative therapy settings to treat solid tumors and cancers. In this work, a novel in-syringe-based fast drug extraction (IS-FaDEx) technique followed by UHPLC-MS/MS detection was developed for rapid biomonitoring of 5-FU and its biometabolites in human blood samples.
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