Synthesis and biological evaluation of Vinpocetine derivatives |
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| Affiliation: | 1. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China;2. School of Pharmaceutical Sciences, Guizhou University of Traditional Chinese Medicine, Guiyang 550002, China;3. Department of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Shenyang 110016, China;1. School of Pharmacy, Fujian University of Traditional Chinese Medicine, 1 Qiuyang Road, Fuzhou, Fujian 350122, People’s Republic of China;2. Department of Medicinal Chemistry, School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, People’s Republic of China;3. Department of Clinical Nutrition, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai 200433, People’s Republic of China;1. Laboratory of Chemical Biology, Department of Studies in Organic Chemistry, University of Mysore, Manasagangotri, Mysore 570006, India;2. Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 117600, Singapore;3. Adichunchanagiri Institute for Molecular Medicine, BG Nagara-571448, NagamangalaTaluk, Mandya District, India;4. Department of Studies in Chemistry, University of Mysore, Manasagangotri, Mysore 570006, India;1. Jiangsu Key Laboratory for Functional Substance of Chinese Medicine, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Stake Key Laboratory Cultivation Base for TCM Quality and Efficacy, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, PR China;2. State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, PR China;3. University of Chinese Academy of Sciences, Beijing, 100049, PR China;1. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Science, Peking University, Beijing, 100191, PR China;2. Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100193, PR China;3. Department of Chemistry, University of Warwick, Coventry, CV4 7AL, United Kingdom;4. College of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Shenyang, 110016, PR China;5. Guangdong-Macau Traditional Chinese Medicine Technology Industrial Park Development Co., Ltd, Zhuhai, 519000, PR China |
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| Abstract: | A new series of Vinpocetine derivatives were synthesized and evaluated for their inhibitory activity on PDE1A in vitro. Seven compounds with higher inhibitory activity were selected for surface plasmon resonance (SPR) binding experiments. Compared with Vinpocetine, these high potency compounds presented a higher binding affinity with PDE1A, which was consistent with inhibitory activity. After further screening, compounds 5, 7, 21, 34 and Vinpocetine were selected to examine the vasorelaxant effects on endothelium-intact rat thoracic aortic rings. The study suggested that the effects of compounds 7 and 21 were the most significant with the maximum value of 93.46 ± 0.77% and 92.90 ± 0.78% (n = 5) at a concentration of 100 μM respectively. Based on these studies, compounds 7 and 21 were considered for further development as hit compounds. |
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| Keywords: | Vinpocetine Structural modification PDE1A |
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