Synthesis and evaluation of new 3-phenylcoumarin derivatives as potential antidepressant agents |
| |
| Institution: | 1. Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute (CSIR-CDRI), BS-10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India;2. Pharmacology Division, CSIR-Central Drug Research Institute (CSIR-CDRI), BS-10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India;3. Pharmacokinetics and Metabolism Division, CSIR-Central Drug Research Institute (CSIR-CDRI), BS-10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226 031, India;1. Department of Medical Research, SRM Medical College Hospital Research Centre, SRM University, Kattankulathur, 603203, Kancheepuram District, Tamil Nadu, India;2. Department of Animal House, SRM Medical College Hospital Research Centre, SRM University, Kattankulathur, 603203, Kancheepuram District, Tamil Nadu, India;3. Department of Veterinary Pathology, Tamil Nadu Veterinary Animal Sciences University, Tamil Nadu, India;1. Department of Orthopedic Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan;2. Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan;3. Department of Clinical Laboratory, National Center for Geriatrics and Gerontology, Obu, Aichi 474-8511, Japan;1. Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 4, 770 Sumneytown Pike, West Point, PA 19486, United States;2. Department of In Vitro Pharmacology, Merck Research Laboratories, PO Box 4, 770 Sumneytown Pike, West Point, PA 19486, United States;3. Department of Neuroscience, Merck Research Laboratories, PO Box 4, 770 Sumneytown Pike, West Point, PA 19486, United States;4. Department of In Vivo Pharmacology, Merck Research Laboratories, PO Box 4, 770 Sumneytown Pike, West Point, PA 19486, United States;5. Department of Drug Metabolism, Merck Research Laboratories, PO Box 4, 770 Sumneytown Pike, West Point, PA 19486, United States;6. Department of Basic Pharmaceutical Sciences, Merck Research Laboratories, PO Box 4, 770 Sumneytown Pike, West Point, PA 19486, United States;1. Laboratory of Pharmacology of Natural and Synthetic Products, Institute of Biological Sciences, Federal University of Goiás, Campus Samambaia, Goiânia, GO, Brazil;2. Laboratory of Medicinal Pharmaceutical Chemistry, Faculty of Pharmacy, Federal University of Goiás, Goiânia, GO, Brazil;3. Chemistry Institute, Federal University of Goiás, Campus Samambaia, Goiânia, GO, Brazil;4. Department of Physiological Sciences, Institute of Biology, Federal Rural University of Rio de Janeiro, Seropédica, RJ, Brazil;5. Center of Biotechnology, Federal University of Rio Grande do Sul, RS, Brazil |
| |
| Abstract: | A series of amine substituted 3-phenyl coumarin derivatives were designed and synthesized as potential antidepressant agents. In preliminary screening, all compounds were evaluated in forced swimming test (FST), a model to screen antidepressant activity in rodents. Among the series, compounds 5c and 6a potentially decreased the immobility time by 73.4% and 79.7% at a low dose of 0.5 mg/kg as compared to standard drug fluoxetine (FXT) which reduced the immobility time by 74% at a dose of 20 mg/kg, ip. Additionally, these active compounds also exhibited significant efficacy in tail suspension test (TST) (another model to screen antidepressant compounds). Interestingly, rotarod and locomotor activity tests confirmed that these two compounds do not have any motor impairment effect and neurotoxicity in mice. Our studies demonstrate that the new 3-phenylcoumarin derivatives may serve as a promising antidepressant lead and hence pave the way for further investigation around this chemical space. |
| |
| Keywords: | Forced swim test Tail suspension test Depression Coumarin |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
