Synthesis,and anti-proliferative,Pim-1 kinase inhibitors and molecular docking of thiophenes derived from estrone |
| |
| Institution: | 1. Department of Chemistry, Faculty of Science, Cairo University, Giza, Egypt;2. National Organization for Drug Control & Research, P.O. 29, Cairo, Egypt;3. Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt;1. Amakem Therapeutics N.V., Agoralaan Abis, 3590 Diepenbeek, Belgium;2. Laboratory of Ophthalmology, KU Leuven, 3000 Leuven, Belgium;1. Department of Pharmacology, University of Illinois at Chicago College of Medicine, Chicago, IL;2. Faculty of Health Sciences, Curtin University, Perth, Australia;3. Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China;1. EA GICC - ERL 7001 CNRS « Groupe Innovation et Ciblage Cellulaire », Team Innovation Moléculaire et Thérapeutique, University of Tours, F-37200, Tours, France;2. CNRS ERL7001 LNOx « Leukemic Niche and RedOx Metabolism » - EA GICC, University of Tours, F-37000, Tours, France;3. CHRU de Tours, Service d’Hématologie Biologique, F-37044, Tours, France;4. Université de Nantes, Nantes Atlantique Universités, Département de Chimie Thérapeutique, Cibles et Médicaments des Infections et du Cancer, IICIMED- EA1155, Institut de Recherche en Santé 2, F-44200, Nantes, France;5. UMR University of Orléans-CNRS 7311, Institut de Chimie Organique et Analytique (ICOA), University of Orléans, F-45067, Orléans, France;6. Sorbonne Universités, USR3151 CNRS/UPMC, Plateforme de criblage KISSf (Kinase Inhibitor Specialized Screening Facility), Station Biologique, Place Georges Teissier, F-29688, Roscoff, France;7. UMR-S 1172 - JPArc - Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer, University of Lille, Inserm, CHU Lille, F-59000, Lille, France;1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt;2. Department of Pharmaceutical Chemistry, Faculty of Pharmacy & Drug Manufacturing, Pharos University in Alexandria, Alexandria, Egypt;3. Medical Biotechnology Department, Genetic Engineering and Biotechnology Research Institute, City of Scientific Research and Technological Applications (SRTA-City), Egypt;1. Department of Pharmaceutical Sciences, Faculty of Pharmacy, Zarqa University, Azzarqa, Jordan;2. Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Hashemite University, Az-zarqa, Jordan;3. Department of Pharmaceutical Sciences, Faculty of Pharmacy, University of Jordan, Amman, Jordan;4. Department of Pharmacology, Faculty of Medicine, University of Jordan, Amman, Jordan |
| |
| Abstract: | Heterocyclization of steroids were reported to give biologically active products where ring D modification occured. Estrone (1) was used as a template to develop new heterocyclic compounds. Ring D modification of 1 through its reaction with cyanoacetylhydrazine and elemental sulfur gave the thiophene derivative 3. The latter compound reacted with acetophenone derivatives 4a-c to give the hydrazide-hydrazone derivatives 5a-c, respectively. In addition, compound 3 formed thiazole derivatives through its first reaction with phenylisothiocyanate to give the thiourea derivative 9 followed by the reaction of the later with α-halocarbonyl compounds. In the present work a series of novel estrone derivatives were designed, synthesized and evaluated for their in vitro biological activities against c-Met kinase, and six typical cancer cell lines (A549, H460, HT-29, MKN-45, U87MG and SMMC-7721). The most promising compounds 5b, 5c, 11a, 13c, 15b, 15c, 15d, 17a and 17b were further investigated against the five tyrosine kinases c-Kit, Flt-3, VEGFR-2, EGFR, and PDGFR. Compounds 5b, 15d, 17a and 17b were selected to examine their Pim-1 kinase inhibition activity where compounds 15d and 17b showed high activities. Molecular docking of some of the most potent compounds was demonstrated. |
| |
| Keywords: | Estrone Thiophene Thiazole Pyridine Anti-proliferative Pim-1 kinase inhibitors |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
