Design and synthesis of 1,2,3-triazolo-phenanthrene hybrids as cytotoxic agents |
| |
| Institution: | 1. Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India;2. Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India;1. Department of Medicinal Chemisry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan 255012, China;2. Shandong Qidu Pharmaceutical Co. Ltd., Shandong Provincial Key Laboratory of Neuroprotective Drugs, Zibo 255400, China;1. Idenix SARL, an MSD Company, Medicinal Chemistry Laboratory, Cap Gamma, 1682 rue de la Valsière, BP50001, 34189 Montpellier Cedex 4, France;2. Former Idenix employee;1. Institute of Organic Chemistry, Johannes Gutenberg University Mainz, Duesbergweg 10-14, 55128, Mainz, Germany;2. MAterial Science IN MainZ (MAINZ), Graduate School of Excellence, Staudingerweg 9, 55128, Mainz, Germany;1. Institute of Drug Discovery and Development, East China Normal University, Shanghai 200062, PR China;2. Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, East China Normal University, Shanghai 200062, PR China;3. State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China;4. National Center for Drug Screening, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China;1. Department of Organic Chemistry, Chemistry Institute, UNAM, Circuito exterior S.N., Ciudad Universitaria, Coyoacán, México DF 04510, Mexico;2. Universidad Tecnológica de México-UNITEC MÉXICO – Campus Marina-Cuitláhuac, Norte 67 No. 2346, San Salvador Xochimanca, Azcapotzalco, DF 02870, Mexico |
| |
| Abstract: | A series of new 1,2,3-triazolo-phenanthrene hybrids has been synthesized by employing Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. These compounds were evaluated for their in vitro cytotoxic potential against various human cancer cell lines viz. lung (A549), prostate (PC-3 and DU145), gastric (HGC-27), cervical (HeLa), triple negative breast (MDA-MB-231, MDA-MB-453) and breast (BT-549, 4T1) cells. Among the tested compounds, 7d displayed highest cytotoxicity against DU145 cells with IC50 value of 1.5 ± 0.09 µM. Further, the cell cycle analysis shown that it blocks G0/G1 phase of the cell cycle in a dose dependent manner. In order to determine the effect of compound on cell viability, phase contrast microscopy, AO/EB, DAPI, DCFDA and JC-1 staining studies were performed. These studies clearly indicated that the compound 7d inhibited the cell proliferation of DU145 cells. Relative viscosity measurements and molecular docking studies indicated that these compounds bind to DNA by intercalation. |
| |
| Keywords: | 1 2 3-Triazoles Phenanthrene Cytotoxicity Click reaction DNA interaction |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
