Synthesis of 5-enamine-4-thiazolidinone derivatives with trypanocidal and anticancer activity |
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| Institution: | 1. Department of Pharmaceutical, Organic and Bioorganic Chemistry, Danylo Halytsky Lviv National Medical University, 69 Pekarska, Lviv 79010, Ukraine;2. Department of Chemistry, Ivano-Frankivsk National Medical University, 2 Halytska, Ivano-Frankivsk 76018, Ukraine;3. Department of Organic Chemistry, Poznan University of Medical Sciences, Grunwaldzka 6, 60-780 Poznan, Poland;4. National Museum of Natural History, UMR 7245 CNRS-MNHN, Team APE, CP 52, 57 Rue Cuvier, Paris 75005, France;5. Department of Public Health, Dietetics and Lifestyle Disorders, Faculty of Medicine, University of Information Technology and Management in Rzeszow, Sucharskiego 2, 35-225 Rzeszow, Poland;6. Department of Organic Chemistry and Pharmacy, Lesya Ukrainka Eastern European National University, Volya Avenue 13, 43025 Lutsk, Ukraine;1. Science and Technology Unit (STU), Umm Al-Qura University, Makkah, 21955, Saudi Arabia;2. Department of Pharmaceutics, Faculty of Pharmacy, Umm Al-Qura University, Makkah, 21955, Saudi Arabia;3. Department of Pharmaceutics, Faculty of Pharmacy, Minia University, Minia, 61519, Egypt;4. Department of Pharmacology, Faculty of Pharmacy, Umm Al-Qura University, Makkah, 21955, Saudi Arabia;5. Department of Pharmacology, Medicinal and Aromatic Plants Research Institute, National Center for Research, Khartoum, 2404, Sudan;6. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Umm Al-Qura University, Makkah, 21955, Saudi Arabia;7. Medicinal Chemistry Department, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, 62514, Egypt;1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt;2. Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Drug Manufacturing, Pharos University in Alexandria, Alexandria, Egypt;3. Genetic Engineering and Biotechnology Research Institute (GEBRI), City of Scientific Research and Technological Applications (SRTA-City), Alexandria, Egypt;1. Institute of Pharmacology and Toxicology, Antona Tsedika 14, 03057, Kyiv, Ukraine;2. Department of Pharmaceutical, Organic and Bioorganic Chemistry, Danylo Halytsky Lviv National Medical University, Pekarska 69, 79010, Lviv-10, Ukraine;3. Department of Public Health, Dietetics and Lifestyle Disorders, Faculty of Medicine, University of Information Technology and Management in Rzeszow, Sucharskiego 2, 35-225, Rzeszow, Poland;4. The Community for Open Antimicrobial Drug Discovery (CO-ADD), Centre for Superbug Solutions, Institute for Molecular Bioscience, The University of Queensland, Brisbane, 4072, Australia;5. Nizhyn Mykola Gogol State University, Grafska 2, Nizhyn, Ukraine;1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Babu Banarasi Das Northern India Institute of Technology, BBD City, Faizabad Road, Lucknow 226028, U.P., India;2. Pharmacy Department, Faculty of Technology and Engineering, The M.S. University of Baroda, Kala Bhavan, Vadodara 390001, Gujarat, India;1. Department of Pharmaceutical, Organic and Bioorganic Chemistry, Danylo Halytsky Lviv National Medical University, 69 Pekarska, Lviv, 79010, Ukraine;2. Enamine Ltd, 23 Alexandra Matrosova, Kiev, 01103, Ukraine;3. Department of Organic Chemistry, Poznan University of Medical Sciences, Grunwaldzka 6, Poznan, 60-780, Poland |
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| Abstract: | A series of novel 2-(5-aminomethylene-4-oxo-2-thioxothiazolidin-3-yl)-3-phenylpropionic acid ethyl esters has been synthesized. Target compounds were evaluated for their trypanocidal activity towards Trypanosoma brucei brucei and Trypanosoma brucei gambiense. Several hit-compounds (8, 10, 12) inhibited growth of the parasites at sub-micromolar concentrations (IC50 0.027–1.936 µM) and showed significant selectivity indices (SI = 108–1396.2) being non-toxic towards the human primary fibroblasts. The screening of anticancer activity in vitro within NCI DTP protocol allowed to identify active 2-(5-{5-(2,4-dichlorobenzyl)-thiazol-2-ylamino]-methylene}-4-oxo-2-thioxothiazolidin-3-yl)-3-phenylpropionic acid ethyl ester 14 that demonstrated inhibition against all 59 human tumor cell lines with the average GI50 value of 2.57 μM. It was established that the activity type (antitrypanosomal or anticancer) as well as its level depends on the character of enamine fragment in the C5 position of thiazolidinone core. |
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| Keywords: | 5-ene-4-thiazolidinones Antitrypanosomal activity Anticancer activity X-ray |
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