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Richard K. Amewu BSc(Ghana), MSc,PhD(Chemistry)(UK)

Richard K. Amewu BSc(Ghana), MSc,PhD(Chemistry)(UK)
Senior Lecturer
ramewu@ug.edu.gh
8661

 

Richard’s research interest is in the development of novel therapeutic agents for neglected diseases. Richard is a synthetic organic chemist with special interest in drug-design, chemical biology and medicinal chemistry of antimalarial, antimycobacterial, and anticancer drugs as well as treatment of other neglected diseases.

Richard’s research also focuses on exploring the key pharmacophore in natural products and designing semi synthetic or purely synthetic analogues that mimic natural products as well as manipulation of undruglike chemical entities with therapeutic properties in to druglike compounds.

Richard’s research is part of a global drug discovery team consisting of medicinal chemists, computational chemists, natural product chemist structural biochemists and pharmacologists.

 

Current Projects

  • Synthesis and Antimalarial Evaluation of Derivatives of SFK78 (MMV902507) and SFG29 (MMV900330) chemical series.
  • Medicinal chemistry progression of MMV696444 identified from the MMV Pathogen Box for malaria and tuberculosis.
  • Control, elimination, and eradication of NTDs in Ghana (Buruli ulcer, leprosy, and yaws.
  • Better Health Outcomes for Buruli Ulcer Patients: Improved diagnostics coupled with better education.
  • Synthesis and Antimalarial Evaluation of Derivatives of MMV1794959 chemical series. 
  • Evaluation of fluorescent Thin Layer Chromatography and PCR for Diagnosis of Burili Ulcer.
  • Discovering new leads for innovative drugs against neglected tropical diseases from the pathogen box (MMV019721, MMV020136 and MMV676444).
  • Synthesis and antimycobacterial/antimalarial activities in vitro of isonicotinohydrizides.

Other Major Projects

  • Drug Development of Positive Allosteric Modulators (PAMS) of Strychnine-Sensitive Glycine Receptors - A New Concept in Treating Chronic Pain.
  • MMV Discovery Project: Identification of a Tetraoxane Drug Development Candidate for Uncomplicated Malaria.
  • MRC-funded TB drug development.
  • Wellcome Trust (Seeding Drug Discovery). Alternative complex I as a new drug target against malaria.
  • EU Sponsored Development of new treatment for malaria-AntiMal FP6 Malaria Drug Initiative.
  • Development of a new synthetic route to antimalarial 1,2,4-trioxanes, 1,2,4-trioxepanes and rational design of orally bio-available 1,2,4,5-tetraoxanes.

Patent, Publications and Book Chapter

Patents

  1. O’neill Paul, Biagini Giancarlo; Ward Stephen A.; Berry Neil Graham; Nixon Gemma; Amewu Richard K.; Pidathala Chandrakala; Hong Weiqian David; Gibbons Peter; Leung Suet Ching; Pacorel Benedicte; Sharma Raman;  Lawrenson Alexander; Shone Alison; Srivastava Abhishek; Warman Ashley. Antimalarial compounds, 2012, WO2012069856 (A1).
  2. Amewu Richard; Marti Francecs; Ward Stephen Andrew; O'neill Paul. Preparation of dispirocyclohexanyltetraoxanylcycloalkylphenol derivatives and analogs for use as antimalarials. 2010, WO2010109172 (A1).
  3. Richard Amewu; O'Neill, Paul Michael; Stachulski, Andrew; Ellis, Gemma; Ward, Stephen Andrew Preparation of dispiro-tetraoxane compounds for the treatment of malaria and/or cancer. 2008, WO2008038030 A2.
  4. O'Neill, Paul M.; Amewu, Richard; Mukhtar, Amira; Ward, Stephen A. 1,2,4-Trioxanes and 1,2,4-trioxepanes. 2005, US20050256184 A1.

    Publications

  1.  Patrick O Sakyi, Richard K Amewu, Robert NOA Devine, Alfred K Bienibuor, Whelton A Miller, Samuel K Kwofie, Unravelling the myth surrounding sterol biosynthesis as plausible target for drug design against leishmaniasis, Journal of Parasitic Diseases, 2021, https://doi.org/10.1007/s12639-021-01390-1
  2. Patrick O Sakyi, Richard K Amewu, Robert NOA Devine, Emahi Ismaila, Whelton A Miller, Samuel K Kwofie, The Search for Putative Hits in Combating Leishmaniasis: The Contributions of Natural Products Over the Last  Decade, Natural Products and Bioprospecting, 2021, 11(5):489-544. doi: 10.1007/s13659-021-00311-2
  3. Affo Dermane, Kafui Kpegba, Kodjo Eloh, Dorcas Osei-Safo, Richard K. Amewu, Pierluigi Caboni 2020, Differential constituents in roots, stems and leaves of Newbouldia laevis Thunb. screened by LC/ESI-Q-TOF-MS    Results in Chemistry, 2 (2020) 100052 https://doi.org/10.1016/j.rechem.2020.100052
  4. De Rycker M, Horn D, Aldridge B, Amewu RK, Barry CE 3rd, Buckner FS, Cook S, Ferguson MAJ, Gobeau N, Herrmann J, Herrling P, Hope W, Keiser J, Lafuente-Monasterio MJ, Leeson PD, Leroy D, Manjunatha UH, McCarthy J, Miles TJ, Mizrahi V, Moshynets O, Niles J, Overington JP, Pottage J, Rao SPS, Read KD, Ribeiro I, Silver LL, Southern J, Spangenberg T, Sundar S, Taylor C, Van Voorhis W, White NJ, Wyllie S, Wyatt PG, Gilbert    IH, Setting Our Sights on Infectious Diseases. 2020 ACS Infect Dis. 6, 1, 3-13. doi: 10.1021/acsinfecdis.9b00371.
  5. Paul M. O’ Neill, Paul A. Stocks, Sunil Sabbani, Natalie L. Roberts, Richard K. Amewu, Emma R. Shore, Ghaith Aljayyoussi, Iñigo Angulo-Barturén, María Belén, Jiménez-Díaz, Santiago Ferrer Bazaga, María Santos Martínez, Brice Campo, Raman Sharma, Susan A. Charman, Eileen Ryan, Gong Chen, David M. Shackleford, Jill Davies, Gemma L. Nixon, Giancarlo A. Biagini, Stephen A. Ward. Synthesis and profiling of                            benzylmorpholine 1,2,4,5-tetraoxane analogue N205: Towards tetraoxane scaffolds with potential for single dose cure of malaria Bioorganic & Medicinal Chemistry 2018, 26, 11, 2996-3005. doi.org/10.1016/j.bmc.2018.05.006
  6. Paul O'Neill, Richard Amewu, Susan Charman, Sunil Sabbani, Nina Gnädig, Judith Straimer, David Fidock, Emma Shore, Natalie Roberts, Michael Wong, W. David Hong, Chandra Pidathala, Chris Riley, Ben Murphy, Ghaith Aljayyoussi, Francisco-Javier Gamo, Laura Maria Sanz, Janneth Rodrigues, Carolina Gonzalez Cortes, Esperanza Herreros, Inigo Angulo-Barturen, Maria Jimenez-Diaz, Santiago Ferrer, Maria Santos Martinez, Brice Campo, Raman Sharma, Eileen Ryan, David Shackleford, Simon Campbell, Denis Smith, Grennady Wirjanata, Rintis Noviyanti, Ric Price, Jutta Marfurt, Michael Palmer, Ian Copple, Amy Mercer, Andrea Ruecker, Michael Delves, Robert Sinden, Peter Siegl, Jill Davies, Rosemary Rocheford, Clemens Kocken, Anne-Marie Zeeman, Gemma Nixon, Giancarlo Biagini, and Stephen Ward. A tetraoxane-based antimalarial drug candidate that overcomes PfK13-C580Y dependent artemisinin resistance. Nature Communication, 2017, 8, 15159 DOI: 10.1038/ncomms15159
  7. Dorcas Osei-Safo, Godwin Akpeko Dziwornu, Regina Appiah-Opong, Mary Anti Chama, Isaac Tuffour, Reiner Waibel, Richard Amewu, Ivan Addae-Mensah Constituents of the Roots of Dichapetalum pallidum and Their Anti-Proliferative Activity Molecules, 2017, 22, 4, 532/1-532/11 doi:10.3390/molecules22040532
  8. Hong Weiqian David, Gibbons Peter, Leung Sue, Amewu Richard, Stocks Paul, Stachulski Andrew, Horta Pedro, Cristiano Maria Lurdes, Shone Alison, Moss Darren, Ardrey Alison, Sharma Raman, Warman Ashley, Bedingfield Paul, Fisher Nicholas, Aljayyoussi Ghaith, Mead Sally, Caws Maxine, Berry Neil, Ward Stephen, Biagini Giancarlo, O'Neill Paul M.,  Nixon Gemma. Rational Design, Synthesis and Biological Evaluation of            Heterocyclic Quinolones Targeting the respiratory chain of Mycobacterium tuberculosis.  Journal of Medicinal Chemistry, 2017, 60, 9, 3703-3726 DOI: 10.1021/acs.jmedchem.6b01718
  9. Paul M. O' Neill , Sunil Sabbani, Gemma L. Nixon, Matthew Schnaderbeck, Natalie L. Roberts, Emma R. Shore, Christopher Riley, Ben Murphy, Paul McGillan, Stephen A. Ward, Jill Davies, Richard K. Amewu Optimisation  of the synthesis of second generation 1,2,4,5 tetraoxane antimalarials. Tetrahedron, 2016, 72, 40, 6118-6126. dx.doi.org/10.1016/j.tet.2016.08.043
  10. Antoine, Thomas, Fisher, Nicholas, Amewu, Richard, O'Neill, Paul, Ward, Steve, Biagini, Giancarlo Rapid kill of malaria parasites by artemisinin and semi-synthetic endoperoxides involves ROS-dependent depolarization of membrane potential. Journal of Antimicrobial Chemotherapy, 2014, 69, 4, 1005-1016. doi:10.1093/jac/dkt486
  11. Miranda Daniela, Capela Rita, Albuquerque Inês, Paiva Isa, Nogueira Fátima, Amewu, Richard, Gut, Jiri, Rosenthal, Philip, Oliveira, Rudi Mota Maria, Moreira Rui, Marti Francesc, Prudêncio Miguel, O’Neill Paul, Lopes      Francisca, Novel endoperoxide-based transmission-blocking, antimalarials with liver- and blood-schizontocidal activities. Medicinal Chemistry Letters, 2014, 5, 2, 108-112. doi.org/10.1021/ml4002985
  12. Richard Kwamla Amewu, James Chadwick; Afthab Hussain; Somnath Panda; Rinki Rinki; Omar Janneh; Stephen A Ward; Candel Miguel; Hollie Burrel-Saward; Livia Vivas; Paul M O'Neill Synthesis and Evaluation of the    Antimalarial, Anticancer, and Caspase 3 Activities of Tetraoxane Dimers. Bioorganic & Medicinal Chemistry 21, 23, 2013, 7392-7397. http://dx.doi.org/10.1016/j.bmc.2013.09.047
  13. Rudi Oliveira, Ana S. Newton, Rita C. Guedes, Daniela Miranda, Richard K. Amewu, Abhishek Srivastava, Jiri Gut, Philip J. Rosenthal, Paul M. O’Neill, Stephen A. Ward, Francisca Lopes, and Rui Moreira An Endoperoxide-Based Hybrid Approach to Deliver Falcipain Inhibitors Inside Malaria Parasites. ChemMedChem 2013, 8, 1528 – 1536. DOI: 10.1002/cmdc.201300202
  14. Giancarlo A. Biagini, Nicholas Fisher, Alison E. Shone, Murad A. Mubaraki, Abhishek Srivastava, Alisdair Hill, Thomas Antoine, Ashley J. Warman, Jill Davies, Chandrakala Pidathala, Richard K. Amewu, Suet C. Leung,      Raman Sharma, Peter Gibbons, David W. Hong, Bénédicte Pacorel, Alexandre S. Lawrenson, Sitthivut Charoensutthivarakul, Lee Taylor, Olivier Berger, Alison Mbekeani, Paul A. Stocks, Gemma L. Nixon, James                  Chadwick, Janet Hemingway,, Michael J. Delves, Robert E. Sinden, Anne-Marie Zeeman, Clemens H. M. Kocken, Neil G. Berry, Paul M. O’Neill, and Stephen A. Ward. Generation of quinolone antimalarials targeting the      Plasmodium falciparum mitochondrial respiratory chain for the treatment and prophylaxis of malaria. Proceedings of the National Academy of Sciences of the United States of America   2012, 109, 21, 8298-8303.        doi/10.1073/pnas.1205651109
  15. Raman Sharma, Alexandre S. Lawrenson, Nicholas E. Fisher, Ashley J. Warman, Alison E. Shone, Alasdair Hill, Alison Mbekeani, Chandrakala Pidathala, Richard K. Amewu, Suet Leung, Peter Gibbons, David W. Hong, Paul Stocks, Gemma L. Nixon, James Chadwick, Joanne Shearer, Ian Gowers, David Cronk, Serge P. Parel, Paul M. O'Neill, Stephen A. Ward, Giancarlo A. Biagini,and Neil G. Berry. Identification of Novel Antimalarial          Chemotypes via Chemoinformatic Compound Selection Methods for a High-Throughput Screening Program against the Novel Malarial Target, PfNDH2: Increasing Hit Rate via Virtual Screening Methods. Journal of        Medicinal Chemistry 2012, 55, 7, 3144-3154 dx.doi.org/10.1021/jm3001482
  16. Chandrakala Pidathala, Richard Amewu, Bénédicte Pacorel, Gemma L. Nixon, Peter Gibbons, W. David Hong, Suet C. Leung, Neil G. Berry, Raman Sharma, Paul A. Stocks, Abhishek Srivastava, Alison E. Shone, Sitthivut    Charoensutthivarakul, Lee Taylor, Olivier Berger, Alison Mbekeani, Alasdair Hill, Nicholas E. Fisher, Ashley J. Warman, Giancarlo A. Biagini, Stephen A. Ward,and Paul M. O’Neill. Identification, Design and Biological        Evaluation of Bisaryl Quinolones Targeting Plasmodium falciparum Type II NADH:Quinone Oxidoreductase (PfNDH2). Journal of Medicinal Chemistry 2012, 55, 5, 1831-1843. dx.doi.org/10.1021/jm201179h
  17. Suet C. Leung, Peter Gibbons, Richard Amewu, Gemma L. Nixon, Chandrakala Pidathala,W. David Hong, Bénédicte Pacorel, Neil G. Berry, Raman Sharma, Paul A. Stocks, Abhishek Srivastava, Alison E. Shone, Sitthivut    Charoensutthivarakul, Lee Taylor,Olivier Berger, Alison Mbekeani, Alasdair Hill, Nicholas E. Fisher, Ashley J. Warman,Giancarlo A. Biagini, Stephen A. Ward, and Paul M. O’Neill.  Identification, Design and Biological        Evaluation of Heterocyclic Quinolones Targeting Plasmodium falciparum Type II NADH:Quinone Oxidoreductase (PfNDH2). Journal of Medicinal Chemistry 2012, 55, 5, 1844 - 1857 dx.doi.org/10.1021/jm201184h
  18. Fatima Bousejra-El Garah, Michael He-Long Wong, Richard K. Amewu, Sant Muangnoicharoen, James L. Maggs, Jean-Luc Stigliani, B. Kevin Park, James Chadwick, Stephen A. Ward, and Paul M. O’Neill Comparison of    the Reactivity of Antimalarial 1,2,4,5-Tetraoxanes with 1,2,4-Trioxolanes in the Presence of Ferrous Iron Salts, Heme, andFerrous Iron Salts/Phosphatidylcholine. Journal of Medicinal Chemistry 2011, 54, 19, 6443-    6455 dx.doi.org/10.1021/jm200768h
  19. Francesc Marti, James Chadwick, Richard K. Amewu, Hollie Burrell-Saward,b Abhishek Srivastava, Stephen A. Ward, Raman Sharma, Neil Berry and Paul M. O’Neill. Second generation analogues of RKA182: synthetic      tetraoxanes with outstanding in vitro and in vivo antimalarial activities. Medicinal Chemistry Communication, 2011, 2, 661-665. DOI: 10.1039/c1md00102g
  20. James Chadwick, Richard K. Amewu, Francesc Marti, Fatima Bousejra-El Garah, Raman Sharma, Neil G. Berry, Paul A. Stocks, Hollie Burrell-Saward, Sergio Wittlin, Matthias Rottmann, Reto Brun, Donatella Taramelli,      Silvia Parapini, Stephen A. Ward, Paul M. O'Neil. Antimalarial Mannoxanes: Hybrid Antimalarial Drugs with Outstanding Oral Activity Profiles and A Potential Dual Mechanism of Action. ChemMedChem, 2011, 6, 1357–  1361. DOI: 10.1002/cmdc.201100196
  21. Peter Gibbons, Edite Verissimo, Nuna C. Araujo, Victoria Barton, Gemma L. Nixon, Richard K. Amewu, James Chadwick, Paul A. Stocks, Giancarlo A. Biagini, Abhishek Srivastava, Philip J. Rosenthal, Jiri Gut, Rita C.          Guedes, RuiMoreira, Raman Sharma, Neil Berry, M. Lurdes S. Cristiano, Alison E. Shone, Stephen A.Ward, and PaulM. O’Neill. Endoperoxide Carbonyl Falcipain 2/3 Inhibitor Hybrids: Toward Combination Chemotherapy  of Malaria through a Single Chemical Entity. Journal of Medicinal Chemistry, 2010, 53, 8202–8206. DOI: 10.1021/jm1009567
  22. Paul M. O'Neill, Richard K. Amewu, Gemma L. Nixon, Fatima Bousejra ElGarah, Mathirut Mungthin, James Chadwick, Alison E. Shone, Livia Vivas, Hollie Lander, Victoria Barton, Sant Muangnoicharoen, Patrick G. Bray,    Jill Davies, B. Kevin Park, Sergio Wittlin, Reto Brun, Michael Preschel, Kesheng Zhang, Stephen A. Ward. Identification of a 1,2,4,5-Tetraoxane Antimalarial Drug-Development Candidate (RKA 182) with Superior Properties to the Semisynthetic Artemisinins.  Angewandte Chemie International Edition, 2010, 49, 33,  5693–5697. DOI: 10.1002/anie.201001026
  23. Richard Amewu, Peter Gibbons, Amira Mukhtar, Andrew V. Stachulski, Stephen A. Ward, Charlotte Hall, Karen Rimmer, Jill Davies, Livia Vivas, John Bacsa, Amy E. Mercer, Gemma Nixon, Paul A. Stocks and Paul M.          O’Neill. Synthesis, in vitro and in vivo antimalarial assessment of sulfide, sulfone and vinyl amide-substituted 1,2,4-trioxanes prepared via thiol-olefin co-oxygenation (TOCO) of allylic alcohols. Organic and                 Biomolecular Chemistry, 2010, 8, 2068–2077. DOI: 10.1039/b924319d
  24. Nicholas Fisher, Alasdair Hill, Alison Mbekeani, Alison Shone, Gemma Nixon, Paul Stocks, Peter Gibbons, Richard Amewu, W. David Hong, Victoria Barton, Chandra Pidathala, James Chadwick, Louise Le Pensee, Ashley  Warman, Raman Sharma, Neil G. Berry, Paul M. O’Neill, Steve A. Ward, Giancarlo A. Biagini. Biochimica et Biophysica Acta (BBA) - Bioenergetics, 2010, 1797, S, 80-80 DOI:10.1016/j.bbabio.2010.04.241
  25. Steve A Ward, Nicholas Fisher, Alasdair Hill, Alison Mbekeani, Alison Shone, Gemma Nixon, Paul Stocks, Peter Gibbons, Richard Amewu, David W Hong, Victoria Barton, Chandra Pidathala, James Chadwick, Louise Le    Pensee, Ashley Warman, Raman Sharma, Neil G Berry, Paul M O'Neill, and Giancarlo A Biagini. A novel drug for uncomplicated malaria: targeted high throughput screening (HTS) against the type II NADH:ubiquinone      oxidoreductase (PfNdh2) of Plasmodium falciparum Malar J. 2010; 9, I14. doi: 10.1186/1475-2875-9-S2-I14
  26. Gemma L. Ellis, Richard Amewu, Sunil Sabbani, Paul A. Stocks, Alison Shone, Deborah Stanford, Peter Gibbons, Jill Davies, Livia Vivas, Sarah Charnaud, Emily Bongard, Charlotte Hall, Karen Rimmer, Sonia Lozanom,      María Jesús, Domingo Gargallo, Stephen A. Ward, and Paul M. O’Neill. Two-Step Synthesis of Achiral Dispiro-1,2,4,5-tetraoxanes with Outstanding Antimalarial Activity, Low Toxicity, and High-Stability Profiles. Journal of Medicinal Chemistry, 2008, 51, 2170–2177. DOI:10.1021/jm701435h
  27. Gemma L. Ellis, Richard Amewu, Charlotte Hall, Karen Rimmer, Steven A. Ward, Paul M. O’Neill. An efficient route into synthetically challenging bridged achiral 1,2,4,5-tetraoxanes with antimalarial activity. Bioorganic  & Medicinal Chemistry Letters, 2008, 18, 1720–1724. doi:10.1016/j.bmcl.2008.01.053
  28. Paul A. Stocks, Patrick G. Bray, Victoria E. Barton, Mohammed Al-Helal, Michael Jones, Nuna C. Araujo, Peter Gibbons, Stephen A. Ward, Ruth H. Hughes, Giancarlo A. Biagini, Jill Davies, Richard Amewu, Amy E. Mercer,  Gemma Ellis, and Paul M. O’Neill. Evidence for a Common Non-Heme Chelatable-Iron-Dependent Activation Mechanism for Semisynthetic and Synthetic Endoperoxide Antimalarial Drugs. Angewandte Chemie              International Edition 2007, 46, 6278 –6283 DOI: 10.1002/anie.200604697
  29. Richard Amewu, Andrew V. Stachulski, Stephen A. Ward, Neil G. Berry, Patrick G. Bray, Jill Davies, Gael Labat, Livia Vivas and Paul M. O’Neill Design and synthesis of orally active dispiro 1,2,4,5-tetraoxanes; synthetic    antimalarials with superior activity to artemisinin.  Organic and Biomolecular Chemistry, 2006, 4, 4431–4436. DOI:10.1039/b613565j
  30. Richard Amewu, Andrew V. Stachulski, Neil G. Berry, Stephen A. Ward, Jill Davies, Gael Labat, Jean-Francois Rossignol, and Paul M. O’Neill. Synthesis of 1,2,4-trioxepanes via application of thiol-olefin Co-oxygenation methodology. Bioorganic & Medicinal Chemistry Letters 2006, 16, 6124–6130. doi:10.1016/j.bmcl.2006.08.098

Book Chapters

  1. Amewu R.K., Spangenberg T. (2021) Detection of Mycolactone by Thin Layer Chromatography. In: Pluschke G., Röltgen K. (eds) Mycobacterium ulcerans. Methods in Molecular Biology, vol 2387. Humana, New York, NY. Springer Protocols. https://doi.org/10.1007/978-1-0716-1779-3_14
  2. Kwaku Kyeremeh, Adrian Flint, Marcel Jaspars, Suthananda Naidu Sunassee, Richard Amewu, Godwin Akpeko Dziwornu, Kojo Sekyi Acquah, Adwoa Nartey Padiki, Rui Krause, Dorcas Osei-Safo, 2020, Making North–      South Collaborations Work: Facilitating Natural Product Drug Discovery in Africa. In: Ramutsindela M., Mickler D. (eds) Africa and the Sustainable Development Goals. Sustainable Development Goals Series. Springer,    Cham DOI: 10.1007/978-3-030-14857-7_24.