Background: New aryl substituted cyclohepta[b]pyridine and cyclohepta[d]pyrimidine derivatives were synthesized. The sugar hydrazones of the synthesized pyridine and pyrimidine compounds were also prepared.
Method: In addition, the 1,3,4-oxadiazolyl acyclic C-nucleoside analogs of the pyridine system were prepared. The hemolytic, prebiotic, anticancer and antimicrobial activities of some of the synthesized compounds were also studied. Compounds 10 and 12 showed high activity against MCF-7, HEPG-2 and HCT-116 cell lines with IC50 at range 3.56-8.55 µg/mL. In addition, the synthesized condensed thiopyrimidine derivative 10 exhibited more potent bactericidal activity while compound 7 demonstrated potent antifungal activity against Aspergillus niger. Furthermore, the synthetic compounds of the pyrimidine base promoted the growth of lactic acid bacteria.
Results: The predicted binding patterns of three of the prepared derivatives as possible antagonists against ERα were investigated which showed good binding patterns.
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http://dx.doi.org/10.2174/1389557518666180820125210 | DOI Listing |
Oncologist
January 2025
Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Thoracic Oncology, 1066 CX Amsterdam, The Netherlands.
Introduction: We describe the safety of sotorasib monotherapy in patients with KRAS G12C-mutated advanced non-small cell lung cancer (NSCLC) and discuss practical recommendations for managing key risks.
Methods: Incidence rates of treatment-related adverse events (TRAEs) were pooled from 4 clinical trials: CodeBreaK 100 (NCT03600883), CodeBreaK 101 (NCT04185883), CodeBreaK 105 (NCT04380753), and CodeBreaK 200 (NCT04303780) and graded according to CTCAE v5.0.
RSC Adv
January 2025
Department of Chemistry, Universidad de Los Andes Carrera 1 No. 18A-10 Bogotá 111711 Colombia
An isomerization reaction of 7-aryl-3-formylpyrazolo[1,5-]pyrimidines to 5-aroyl-NH-pyrazolo[3,4-]pyridines proceeding with high yields in aqueous NaOH under microwave conditions is reported. This unprecedented transformation occurs by adding and eliminating a water molecule an ANRORC mechanism (adding the nucleophile, ring-opening, and ring-closing) studied using DFT calculations. The product's utility was proved as they have aroyl and NH groups that simple methods and readily available reagents easily modified; likewise, their optical properties were studied, highlighting their high potential as highly emissive modular dyes ( up to 99%).
View Article and Find Full Text PDFBMC Infect Dis
January 2025
Clinical and Biomedical Science Department (DIBIC), Infectious Diseases Unit, University of Milan, Legnano General Hospital, ASST Ovest Milanese, Italy, Legnano, 20025, MI, Italy.
Background: Long-acting Cabotegravir and Rilpivirine (LA CAB + RPV) shows potential advantages in heavily comorbid and even in viremic people with HIV (PWH). We assessed LA CAB + RPV durability in a cohort of PWH with a high comorbidity burden and adherence issues.
Methods: Retrospective observational study in two Italian outpatient settings enrolling PWH who switched to LA CAB + RPV from February 2021 to January 2024 in presence of exclusion criteria enlisted in registrational trials or with other worrisome clinical risks.
Pharmacoepidemiol Drug Saf
February 2025
Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
Purpose: The p.G12C mutation in KRAS is commonly found in many cancers and was previously untreatable until drugs like sotorasib were developed. However, up to 15% of patients treated with sotorasib have experienced hepatobiliary adverse events.
View Article and Find Full Text PDFSwiss Med Wkly
January 2025
Cancer Center und Research Center, Cantonal Hospital Graubünden, Chur, Switzerland.
Background And Objective: Because of the lack of effective targeted treatment options, docetaxel has long been the standard second-line therapy for patients with advanced non-small cell lung cancer, including the Kirsten rat sarcoma virus (KRAS) G12C mutation. The CodeBreak 200 trial demonstrated that sotorasib, a new drug targeting the G12C-mutated KRAS protein, modestly improved progression-free survival compared with docetaxel in patients whose cancer had progressed after receiving platinum chemotherapy and programmed cell death protein 1 (PD-1) / programmed death ligand 1 (PD-L1) inhibitors as first-line treatment. Consequently, sotorasib received temporary approval in Switzerland.
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