Literature DB >> 24900843

Plasmepsin inhibitory activity and structure-guided optimization of a potent hydroxyethylamine-based antimalarial hit.

Kristaps Jaudzems1, Kaspars Tars2, Gundars Maurops1, Natalija Ivdra1, Martins Otikovs1, Janis Leitans2, Iveta Kanepe-Lapsa1, Ilona Domraceva1, Ilze Mutule1, Peteris Trapencieris1, Michael J Blackman3, Aigars Jirgensons1.   

Abstract

Antimalarial hit 1 SR (TCMDC-134674) identified in a GlaxoSmithKline cell based screening campaign was evaluated for inhibitory activity against the digestive vacuole plasmepsins (Plm I, II, and IV). It was found to be a potent Plm IV inhibitor with no selectivity over Cathepsin D. A cocrystal structure of 1 SR bound to Plm II was solved, providing structural insight for the design of more potent and selective analogues. Structure-guided optimization led to the identification of structurally simplified analogues 17 and 18 as low nanomolar inhibitors of both, plasmepsin Plm IV activity and P. falciparum growth in erythrocytes.

Entities:  

Keywords:  Cathepsin D; Malaria; Plasmodium falciparum; hydroxyethylamine; inhibition; plasmepsins; structure-guided optimization

Year:  2014        PMID： 24900843      PMCID： PMC4027636          DOI： 10.1021/ml4004952

Source DB:  PubMed          Journal:  ACS Med Chem Lett        ISSN： 1948-5875            Impact factor:   4.345


  19 in total

1.  Potent, low-molecular-weight non-peptide inhibitors of malarial aspartyl protease plasmepsin II.

Authors:  T S Haque; A G Skillman; C E Lee; H Habashita; I Y Gluzman; T J Ewing; D E Goldberg; I D Kuntz; J A Ellman
Journal:  J Med Chem       Date:  1999-04-22       Impact factor: 7.446

2.  Design and synthesis of plasmepsin I and plasmepsin II inhibitors with activity in Plasmodium falciparum-infected cultured human erythrocytes.

Authors:  Daniel Nöteberg; Elizabeth Hamelink; Johan Hultén; Mats Wahlgren; Lotta Vrang; Bertil Samuelsson; Anders Hallberg
Journal:  J Med Chem       Date:  2003-02-27       Impact factor: 7.446

Review 3.  Recent advances in plasmepsin medicinal chemistry and implications for future antimalarial drug discovery efforts.

Authors:  Marvin J Meyers; Daniel E Goldberg
Journal:  Curr Top Med Chem       Date:  2012       Impact factor: 3.295

4.  Synthesis, biological evaluation, and modeling studies of inhibitors aimed at the malarial proteases plasmepsins I and II.

Authors:  Daniel Muthas; Daniel Nöteberg; Yogesh A Sabnis; Elizabeth Hamelink; Lotta Vrang; Bertil Samuelsson; Anders Karlén; Anders Hallberg
Journal:  Bioorg Med Chem       Date:  2005-09-15       Impact factor: 3.641

5.  Effects on growth, hemoglobin metabolism and paralogous gene expression resulting from disruption of genes encoding the digestive vacuole plasmepsins of Plasmodium falciparum.

Authors:  J Alfredo Bonilla; Pedro A Moura; Tonya D Bonilla; Charles A Yowell; David A Fidock; John B Dame
Journal:  Int J Parasitol       Date:  2006-12-15       Impact factor: 3.981

6.  An Invitation to Open Innovation in Malaria Drug Discovery: 47 Quality Starting Points from the TCAMS.

Authors:  Félix Calderón; David Barros; José María Bueno; José Miguel Coterón; Esther Fernández; Francisco Javier Gamo; José Luís Lavandera; María Luisa León; Simon J F Macdonald; Araceli Mallo; Pilar Manzano; Esther Porras; José María Fiandor; Julia Castro
Journal:  ACS Med Chem Lett       Date:  2011-08-03       Impact factor: 4.345

Review 7.  Plasmepsins as potential targets for new antimalarial therapy.

Authors:  Karolina Ersmark; Bertil Samuelsson; Anders Hallberg
Journal:  Med Res Rev       Date:  2006-09       Impact factor: 12.944

8.  Novel uncomplexed and complexed structures of plasmepsin II, an aspartic protease from Plasmodium falciparum.

Authors:  Oluwatoyin A Asojo; Sergei V Gulnik; Elena Afonina; Betty Yu; Jonathan A Ellman; Tasir S Haque; Abelardo M Silva
Journal:  J Mol Biol       Date:  2003-03-14       Impact factor: 5.469

Review 9.  New medicines to improve control and contribute to the eradication of malaria.

Authors:  Timothy N C Wells; Pedro L Alonso; Winston E Gutteridge
Journal:  Nat Rev Drug Discov       Date:  2009-10-16       Impact factor: 84.694

10.  Recombinant plasmepsin 1 from the human malaria parasite plasmodium falciparum: enzymatic characterization, active site inhibitor design, and structural analysis.

Authors:  Peng Liu; Melissa R Marzahn; Arthur H Robbins; Hugo Gutiérrez-de-Terán; David Rodríguez; Scott H McClung; Stanley M Stevens; Charles A Yowell; John B Dame; Robert McKenna; Ben M Dunn
Journal:  Biochemistry       Date:  2009-05-19       Impact factor: 3.162
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  12 in total

Review 1.  Malaria medicines: a glass half full?

Authors:  Timothy N C Wells; Rob Hooft van Huijsduijnen; Wesley C Van Voorhis
Journal:  Nat Rev Drug Discov       Date:  2015-05-22       Impact factor: 84.694

2.  Modeling and resistant alleles explain the selectivity of antimalarial compound 49c towards apicomplexan aspartyl proteases.

Authors:  Budhaditya Mukherjee; Francesca Tessaro; Juha Vahokoski; Inari Kursula; Jean-Baptiste Marq; Leonardo Scapozza; Dominique Soldati-Favre
Journal:  EMBO J       Date:  2018-03-08       Impact factor: 11.598

3.  4-Aryl Pyrrolidines as a Novel Class of Orally Efficacious Antimalarial Agents. Part 1: Evaluation of 4-Aryl- N-benzylpyrrolidine-3-carboxamides.

Authors:  Marvin J Meyers; Jianguang Liu; Jing Xu; Fang Leng; Jiantong Guan; Zhijun Liu; Sarah A McNitt; Limei Qin; Linglin Dai; Hongwei Ma; Dickson Adah; Siting Zhao; Xiaofen Li; Alex J Polino; Armiyaw S Nasamu; Daniel E Goldberg; Xiaorong Liu; Yongzhi Lu; Zhengchao Tu; Xiaoping Chen; Micky D Tortorella
Journal:  J Med Chem       Date:  2019-03-22       Impact factor: 7.446

4.  In vivo anti-malarial activity of the hydroalcoholic extract of rhizomes of Kniphofia foliosa and its constituents.

Authors:  Yonatan Alebachew; Daniel Bisrat; Solomon Tadesse; Kaleab Asres
Journal:  Malar J       Date:  2021-01-01       Impact factor: 2.979

5.  Structures of plasmepsin II from Plasmodium falciparum in complex with two hydroxyethylamine-based inhibitors.

Authors:  Rosario Recacha; Janis Leitans; Inara Akopjana; Lilija Aprupe; Peteris Trapencieris; Kristaps Jaudzems; Aigars Jirgensons; Kaspars Tars
Journal:  Acta Crystallogr F Struct Biol Commun       Date:  2015-11-27       Impact factor: 1.056

6.  Crystal structure of Plasmodium falciparum proplasmepsin IV: the plasticity of proplasmepsins.

Authors:  Rosario Recacha; Kristaps Jaudzems; Inara Akopjana; Aigars Jirgensons; Kaspars Tars
Journal:  Acta Crystallogr F Struct Biol Commun       Date:  2016-08-09       Impact factor: 1.056

7.  In pursuit of new anti-malarial candidates: novel synthesized and characterized pyrano-benzodioxepin analogues attenuated Plasmodium berghei replication in malaria-infected mice.

Authors:  Olubunmi Atolani; Faoziyat Adenike Sulaiman; Abdulmumeen Amao Hamid; Azeezat Alayo; Abraham Cornelius Akina; Simbiat Oloriegbe; Basheer Ajibola Balogun; Gabriel Ademola Olatunji; Learnmore Kambizi
Journal:  Heliyon       Date:  2021-12-02

8.  Study of the antimalarial properties of hydroxyethylamine derivatives using green fluorescent protein transformed Plasmodium berghei.

Authors:  Mariana Conceição Souza; Tatiana Almeida Padua; Natalia Domingos Torres; Maria Fernanda de Souza Costa; Victor Facchinetti; Claudia Regina Brandão Gomes; Marcus Vinícius Nora Souza; Maria das Graças Henriques
Journal:  Mem Inst Oswaldo Cruz       Date:  2015-05-26       Impact factor: 2.743

9.  Oral effectiveness of PMIC4, a novel hydroxyethylpiperazine analogue, in Leishmania amazonensis.

Authors:  Mariela Ferreira de Vasconcelos; Edézio Ferreira da Cunha-Júnior; Valter Viana de Andrade-Neto; Larissa Moreira Siqueira; Cláudia Masini d'Avila-Levy; Marcele Moreth; Wilson Cunico; Marcus Vinícius Nora de Souza; Cláudia Regina Brandão Gomes; Eduardo Caio Torres-Santos
Journal:  Int J Parasitol Drugs Drug Resist       Date:  2014-11-08       Impact factor: 4.077

10.  Hydroxyethylamine Based Phthalimides as New Class of Plasmepsin Hits: Design, Synthesis and Antimalarial Evaluation.

Authors:  Anil K Singh; Sumit Rathore; Yan Tang; Nathan E Goldfarb; Ben M Dunn; Vinoth Rajendran; Prahlad C Ghosh; Neelu Singh; N Latha; Brajendra K Singh; Manmeet Rawat; Brijesh Rathi
Journal:  PLoS One       Date:  2015-10-26       Impact factor: 3.240
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