5-Thioxoimidazolidine-2-one derivatives: Synthesis,anti-inflammatory activity,analgesic activity,COX inhibition assay and molecular modelling study |
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| Affiliation: | 1. Applied Organic Chemistry Department, National Research Centre, Cairo, Egypt;2. Faculty of Science and Arts, Mohail Asser, King Khalid University, Saudi Arabia;3. Organometallic and Organometalloid Chemistry Department, National Research Centre, Cairo, Egypt;4. Chemistry Department, Faculty of Science, Al-Azhar University (Boys), Cairo, Egypt;5. Department of Chemistry, College of Science, United Arab Emirates University, P.O. Box 15551, Al-Ain, United Arab Emirates;6. Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt;7. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt;8. Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt;1. Department of Chemistry, Aligarh Muslim University, Aligarh 202 002, India;2. Department of Chemistry, Govt Degree College Kulgam, Kashmir 192231, India;3. Department of Chemistry, Indian Institute of Technology Powai, Mumbai 400076, India;4. Department of Chemistry, OPJS University, Churu 331001, Rajasthan, India;5. Department of Biochemistry JNMC, Aligarh Muslim University, Aligarh 202 002, India;6. Department of Chemistry, Govt Degree College Anantnag, Kashmir 192101, India;1. Department of Chemistry, Bangalore University, Central College Campus, Palace Road, Bangalore 560001, India;2. Department of Studies in Molecular Biology, University of Mysore, Manasagangotri, Mysore 570006, India;3. Tsinghua Berkeley Shenzhen Institute, Tsinghua University, Shenzhen, Guangdong, PR China;4. Adichunchanagiri Institute for Molecular Medicine, BG Nagara-571448, Nagamangala Taluk, Mandya District, India;5. Department of Studies in Physics, University of Mysore, Manasagangotri, Mysore 570006, India;6. Centre for Molecular Informatics, Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, United Kingdom;7. Department of Studies and Research in Biochemistry, Tumkur University, Tumkur 572101, India;8. Institution of Excellence, Vijnana Bhavan, University of Mysore, Manasagangotri, Mysore 570006, India;9. Department of Studies in Organic Chemistry, University of Mysore, Manasagangotri, Mysore 570006, India;1. Division of Bio-Function Dynamics Imaging, RIKEN Center for Life Science Technologies (CLST), 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan;2. PET Medical Application Group, Central Research Laboratory, Hamamatsu Photonics K.K., 5000 Hirakuchi, Hamakita-ku, Hamamatsu 434-8601, Japan;3. Department of Lipid Signaling, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan;4. Division of Regeneration and Advanced Medical Science, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu 501-1194, Japan;5. Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062, Japan;6. Department of Immunology, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan;7. PET Center, Central Research Laboratory, Hamamatsu Photonics K.K., 5000 Hirakuchi, Hamakita-ku, Hamamatsu 434-8601, Japan;8. Department of Chemistry, Columbia University, 3000 Broadway, New York, NY 10027, USA;9. Department of Clinical and Experimental Neuroimaging, National Center for Geriatrics and Gerontology, Obu, Aichi 474-8511, Japan;1. WuXi AppTec (Shanghai) Co. Ltd., 288 Fute Zhong Road, Shanghai 200131, China;2. Chia Tai Tianqing Pharmaceutical Group Co. Ltd., Building 9, No. 699-8, Xuanwu Road, Nanjing, Jiangsu 210023, China;1. Research Center for Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, People’s Republic of China;2. Guangdong Province Engineering Technology Research Institute of T. C. M., Guangdong Provincial Key Laboratory of Research and Development in Traditional Chinese Medicine, Guangzhou 510095, People’s Republic of China;3. School of Biotechnology and Health Sciences, Wuyi University, 99 Yingbin Road, Jiangmen 529020, People’s Republic of China;4. Guangzhou University of Chinese Medicine, Guangdong Second Traditional Chinese Medicine Hospital, Guangzhou 510095, People’s Republic of China;5. Molecular Laboratory, School of Biomedical Science, University of Western Australia, Perth, Western Australia, Australia |
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| Abstract: | A series of 5-imino-4-thioxo-2-imidazolidinone derivatives with different substituents at N1 and N3 was synthesized with high yield and excellent purity by the reaction of different N-arylcyanothioformamide derivatives with isocyanate derivatives. Treatment 5-imino-4-thioxo-2-imidazolidinone derivatives with acidic medium afforded 4-thioxoimidazolidin-2,5-dione derivatives. The structures of the obtained products were established based on spectroscopic IR, 1H NMR, 13C NMR, 1H, 1H-COSY, HSQC and elemental analyses. The anti-inflammatory activity of the synthesized compounds through the carrageenan-paw edema model as well as in vitro COX-1 and COX-2 inhibition assay were evaluated where most of the synthesized compounds showed significant anti-inflammatory activity. Mostly, all of our synthesized compounds have greater activity more than celecoxib toward both cyclooxygenase enzymes. All of the tested compounds (except one compound) exhibited IC50 valves for COX-2 ranged from 0.001 × 10−3 to 0.827 × 10−3 µM while the reference drug has IC50 40.0 × 10−3 µM. Furthermore, the analgesic activity of such compounds was also determined. Molecular modeling study was also conducted to rationalize the potential as anti-inflammatory agents of our synthesized compounds by predicting their binding modes, binding affinities and optimal orientation at the active site of the COX enzymes. |
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| Keywords: | Imidazolidineiminothiones Imidazolidin-2,5-diones Anti-inflammatory activity Analgesic activity COX inhibition assay |
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