Novel enamine derivatives were synthesized from the reaction of lactone and chalcones and their antiproliferative and cytotoxic activities against six cancer cell lines (e. g., HeLa, HT29, A549, MCF7, PC3 and Hep3B) and one normal cell lines (e. g., FL) were investigated along with their mode of interactions with CT-DNA. Most of the enamine derivatives with IC values of 86-168 μM demonstrated much stronger antiproliferative activity than the starting molecules against the cancer cells. While, among the enamine derivatives, four compounds displayed higher cytotoxic potency than the control drugs (5-fluorouracil and cisplatin) against the Hep3B cell lines, these compounds did not exhibit any significant toxicity against normal cells, FL. The UV/VIS spectral data suggest that eight compounds cause hypochromism with a slight bathochromic shift (∼6 nm), indicating that they bind to the DNA by way of an intercalative or minor groove binding mode. The binding constants of the compounds are in the range of 0.1×103 M -2.3×104 M . The antiproliferative activity of studied enamine derivatives could possibly be due to their DNA binding as well as their cytotoxic properties. In addition to these assays, the chalcones and enamine derivatives were investigated by molecular docking to calculate the synergistic effect of antiproliferative activities against six human cancer cell lines.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1002/cbdv.202000139 | DOI Listing |
Org Lett
December 2024
School of Chemistry & Chemical Engineering, Yangzhou University, Yangzhou, Jiangsu 225002, China.
Using a SbCl/O mild oxidation system, a dual functionalization of the α,β-C-H bonds in alanine ester derivatives was achieved via enamine-imine tautomerism, and a series of quinoline-4-carboxylates were synthesized through a fragmentation-reassembly pathway. The investigation of the substrate scope revealed that various functional groups were easily tolerated, highlighting that this reaction provided an efficient path for the construction of the quinoline-4-carboxylate framework.
View Article and Find Full Text PDFACS Chem Neurosci
January 2025
Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama 35233, United States.
Proinflammatory TREM1 receptors expressed on myeloid-derived cells have recently been recognized as a new oncogenic target in cancer, including gliomas. They are established chemotherapeutic targets in neurodegenerative Parkinson's and Alzheimer's diseases, and they also contribute to stroke and sepsis severities. TREM1 activation requires the TREM1/DAP12 interaction for receptor clustering and signal transduction coordinated by TREM1 ligands.
View Article and Find Full Text PDFCell Chem Biol
November 2024
Institute of Biochemistry II, Medical Faculty, Goethe-University, Frankfurt am Main and Buchmann Institute for Molecular Life Sciences, Frankfurt am Main, Germany; Max Planck Institute of Biophysics, Max-von-Laue-Strasse 3, 60439 Frankfurt am Main, Germany. Electronic address:
J Med Chem
November 2024
Enamine Ltd., Winston Churchill Street 78, 02094 Kyiv, Ukraine.
Proline analogues are versatile chemical building blocks that enable modular construction of small-molecule drugs and pharmaceutical peptides. Over the past 15 years, the FDA has approved over 15 drugs containing proline analogues in their structures, five in the last three years alone (daridorexant, trofinetide, nirmatrelvir, rezafungin, danicopan). This perspective offers an analysis of the most common types of proline analogues currently trending in drug design.
View Article and Find Full Text PDFJ Org Chem
December 2024
Enamine Ltd., Winston Churchill Street 78, Kyïv 02094, Ukraine.
An expedient approach to the synthesis of 4-azaspiro[2.3]hexane derivatives is described. The synthetic scheme consists of Tebbe olefination of -Boc-protected 2-azetidinone (including the first use of the deuterated Petasis reagent CpTi(CD) in the building block preparation) and cyclopropanation of the resulting intermediate.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!