A series of tacrine-rhein hybrid compounds have been designed and synthesized as novel multifunctional potent ChE inhibitors. Most of the compounds inhibited ChEs in the nanomolar range in vitro effectively. Compound 10b was one of the most potent inhibitors and was 5-fold more active than tacrine toward AChE, and it also showed a moderate BuChE inhibition with an IC50 value of 200 nM. Kinetic and molecular modeling studies of 10b also indicated that it was a mixed-type inhibitor binding simultaneously to the active and peripheral sites of AChE. In inhibition of the AChE-induced Aβ aggregation assay, compound 10b (70.2% at 100 μM) showed the greatest inhibitory activity. In addition, 10b showed metal-chelating property and low hepatotoxicity. These results suggested that 10b might be an excellent multifunctional agent for AD treatment.
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http://dx.doi.org/10.1039/c3ob42010h | DOI Listing |
Chem Biodivers
December 2024
Department of Pathology and Cancer Screening, Chittaranjan National Cancer Institute, Kolkata, West Bengal, India.
Arch Pharm (Weinheim)
November 2024
Department of Medicinal Chemistry and Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
Radioprotectors are synthetic compounds, natural products, or biological agents that are administered before irradiation to protect normal cells against ionizing radiation (IR)-induced injuries. We have designed novel hybrid (E)-kojyl-styryl-sulfones 10a-n by applying the pharmacophore hybridization strategy to combine key structural motifs of the natural antioxidant kojic acid and the emerging radioprotector Ex-RAD (recilisib sodium). These hybrids were successfully synthesized and characterized with (E)-geometry.
View Article and Find Full Text PDFFitoterapia
November 2024
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China. Electronic address:
Two undescribed diterpenoids (1-2) and three lignans (3a/3b, 4a), together with sixteen known compounds (4b, 5-9, 10a/10b-14a/14b) were obtained from the stems of Tripterygium wilfordii (T. wilfordii). The structures of these new compounds were elucidated by detailed spectroscopic analyses, and their absolute configurations were estabished by ECD calculations.
View Article and Find Full Text PDFEur J Med Chem
January 2025
Pharmaceutical and Medicinal Chemistry, Saarland University, Campus C2.3, 66123, Saarbrücken, Germany. Electronic address:
Bioorg Chem
December 2024
Department of Science, Institute for Information Technologies Kragujevac, University of Kragujevac, Kragujevac 34000, Serbia. Electronic address:
The aim of the presented research was to explore anticancer potential of eleven newly synthesized tetrahydropyrimidine derivatives. The compounds were synthesized via Biginelli multicomponent one-pot reaction using different derivatives of vanillin, ethyl 4-chloroacetoacetate and (N-methyl)urea. The cytotoxic effects of the compounds were examined on three human malignant cell lines (HeLa, K562, and MCF7), and normal lung fibroblasts MRC-5.
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