Nitrogen-containing derivatives of O-tetramethylquercetin: Synthesis and biological profiles in prostate cancer cell models |
| |
| Institution: | 1. Department of Chemistry, California State University, Fresno, 2555 E. San Ramon Avenue, M/S SB70, Fresno, CA 93740, USA;2. Department of Chemistry, Xavier University of Louisiana, 1 Drexel Drive, New Orleans, LA 70125, USA;3. RCMI Cancer Research Center, Xavier University of Louisiana, 1 Drexel Drive, New Orleans, LA 70125, USA;1. National Facility for High Field NMR, Tata Institute of Fundamental Research, Homi Bhabha Road, Mumbai 400005, India;2. Principal K M Kundnani College of Pharmacy, Cuffe Parade, Mumbai 400005, India;1. Department of Chemistry, California State University, Fresno, 2555 E. San Ramon Avenue, M/S SB70, Fresno, CA 93740, USA;2. RCMI Cancer Research Center Xavier University of Louisiana, 1 Drexel Drive, New Orleans, LA 70125, USA;3. Department of Chemistry, Xavier University of Louisiana, 1 Drexel Drive, New Orleans, LA 70125, USA;1. School of Chemistry, College of Science, University of Tehran, Tehran, Iran;2. Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran;3. Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran;4. Department of Medicinal Chemistry, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran;5. Medicinal Plants and Natural Products Research Center, Hamadan University of Medical Sciences, Hamadan, Iran;6. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran;1. State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Haihe Education Park, 38 Tongyan Road, Tianjin 300353, People’s Republic of China;2. College of Life Sciences, Nankai University, Tianjin 300353, People’s Republic of China;3. Accendatech Company, Ltd., Tianjin 300384, People’s Republic of China;1. Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal;2. Department of Medical Microbiology and Immunobiology, Faculty of Medicine, University of Szeged, Dóm tér 10, H-6720 Szeged, Hungary;3. LAQV@REQUIMTE/Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, Rua do Campo Alegre, 4169-007 Porto, Portugal |
| |
| Abstract: | Forty-eight nitrogen-containing quercetin derivatives were synthesized from readily available rutin or quercetin for the in vitro evaluation of their biological profiles. The WST-1 cell proliferation assay data indicate that thirty-nine out of the forty-eight derivatives possess significantly improved antiproliferative potency as compared with quercetin and fisetin, as well as the parent 3,3′,4′,7-O-tetramethylquercetin toward both androgen-sensitive (LNCaP) and androgen-insensitive (PC-3 and DU145) human prostate cancer cell lines. 5-O-Aminoalkyl-3,3′,4′,7-O-tetramethylquercetins were established as a better scaffold for further development as anti-prostate cancer agents. Among them, 5-O-(N,N-dibutylamino)propyl-3,3′,4′,7-O-tetramethylquercetin (44) was identified as the optimal derivative with IC50 values of 0.55–2.82 µM, being over 35–182 times more potent than quercetin. The flow cytometry-based assays further demonstrate that 44 effectively activates PC-3 cell apoptosis. |
| |
| Keywords: | Quercetin derivative Synthesis Antiproliferative activity Prostate cancer Cell apoptosis |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
