Synthesis of novel chalcones through palladium-catalyzed CO cross-coupling reaction of bromo-chalcones with ethyl acetohydroxamate and their antiplasmodial evaluation against Plasmodium falcipuram in vitro |
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| Affiliation: | 1. Fluoroorganic Laboratory, Centre for Fire, Explosive and Environment Safety, DRDO, Delhi, India;2. Department of Chemistry, University of Delhi, Delhi, India;3. Department of Biochemistry, University of Delhi South Campus, Benito Juarez Road, New Delhi, India;4. Department of Chemistry, Sri Venkateswara College, University of Delhi, New Delhi, India;5. Department of Chemistry, Shivaji College, University of Delhi, New Delhi, India;1. Department of Chemistry and Virginia Tech Center for Drug Discovery, M/C 0212, Virginia Tech, Blacksburg, VA 24061, United States;2. College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju 500-757, Republic of Korea;3. Department of Biochemistry and Molecular Biology, and Center for Tropical and Emerging Global Diseases (CTEGD), University of Georgia, Athens, GA 30602, United States;4. Natural Products Discovery Institute, 2805 Old Easton Road, Doylestown, PA 18902, United States;1. Medicinal & Process Chemistry Division, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India;2. Department of Chemistry, Banasthali University, Banasthali Newai 304022, Rajasthan, India;3. Department of Chemistry, Mohanlal Sukhadia University, Udaipur 313001, India;4. Parasitology Division, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India;5. Department of Chemistry, Manipal University Jaipur, VPO-DehmiKalan, off Jaipur-Ajmer Express Way, Jaipur, Rajasthan, India;1. Department of Chemistry, Guru Nanak Dev University, Amritsar 143005, Punjab, India;2. Department of Medicine, University of California, San Francisco, CA, USA;1. Bose Institute, Division of Molecular Medicine, P-1/12, C.I.T. Scheme VII M, Kolkata 700054, India;1. Centre for Therapeutics Discovery, LifeArc, Accelerator Building, Open Innovation Campus, Stevenage SG1 2FX, UK;2. Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, Keppel Street, London WC1E 7HT, UK;1. College of Pharmacy, Ewha Womans University, Seoul 120-750, Republic of Korea;2. College of Pharmacy, CHA University, Pocheon 487-010, Republic of Korea |
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| Abstract: | An efficient method for palladium-catalyzed C O cross-coupling of ethyl acetohydroxamate (EAcHO) with 4-bromo-chalcones has been developed to synthesize novel chalcones. The two supporting ligands, namely tBuXPhos (L7), and cataCXium®PIntB (L16) were found to be effective ligands towards the Pd-catalyzed CO cross-coupling reaction to afford the desired product in moderate to excellent yields (50–99%). The coupled products were screened for in vitro blood stage antiplasmodial activity against Plasmodium falciparum (3D7) using the [3H] hypoxanthine incorporation inhibition assay. Of the twenty two compounds screened, eleven showed good antiplasmodial activity with IC50 values ranging from 6–16 μg/mL. The selected active molecules 11, 16, 22, (IC50 12 μg/mL) and 19 (IC50 6 μg/mL) were studied for their cytotoxic effect against HepG2 Cells (human hepatocellular liver carcinoma cell lines), showing the selectivity index (SI) values are greater than 4 except chalcone 22. Our result demonstrates a methodology for synthesizing novel chalcones as a new class of antiplasmodial agent. |
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| Keywords: | Pd-catalyzed methodology cataCXium® and PIntB ligands Novel chalcones Ethyl acetohydroxamate Antiplasmodial activity |
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