2. Academic Validation
  3. Synthesis of quinones with highlighted biological applications: A critical update on the strategies towards bioactive compounds with emphasis on lapachones

Synthesis of quinones with highlighted biological applications: A critical update on the strategies towards bioactive compounds with emphasis on lapachones

  • Eur J Med Chem. 2019 Oct 1:179:863-915. doi: 10.1016/j.ejmech.2019.06.056.
Eufrânio N da Silva Júnior 1,  Guilherme A M Jardim 2,  Claus Jacob 3,  Uttam Dhawa 4,  Lutz Ackermann 4,  Solange L de Castro 5
Affiliations

Affiliations

  • 1 Laboratory of Synthetic and Heterocyclic Chemistry, Institute of Exact Sciences, Department of Chemistry, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, 31270-901, Brazil; Institut für Organische und Biomolekulare Chemie, Georg-August-Universität Göttingen, Tammannstraße 2, 37077, Göttingen, Germany. Electronic address: eufranio@ufmg.br.
  • 2 Laboratory of Synthetic and Heterocyclic Chemistry, Institute of Exact Sciences, Department of Chemistry, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, 31270-901, Brazil; Federal University of Santa Catarina, Florianópolis, Santa Catarina, 88040-900, Brazil.
  • 3 Division of Bioorganic Chemistry, School of Pharmacy, Saarland University, Campus B2 1, D-66123, Saarbruecken, Germany.
  • 4 Institut für Organische und Biomolekulare Chemie, Georg-August-Universität Göttingen, Tammannstraße 2, 37077, Göttingen, Germany.
  • 5 Laboratory of Cell Biology, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro, Rio de Janeiro, 21045-900, Brazil.
PMID: 31306817 DOI: 10.1016/j.ejmech.2019.06.056
Abstract

Naphthoquinones are of key importance in organic synthesis and medicinal chemistry. In the last few years, various synthetic routes have been developed to prepare bioactive compounds derived or based on lapachones. In this sense, this review is mainly focused on the synthetic aspects and strategies used for the design of these compounds on the basis of their biological activities for the development of drugs against the neglected diseases leishmaniases and Chagas disease and also Cancer. Three strategies used to develop bioactive Quinones are discussed and categorized: (i) C-ring modification, (ii) redox centre modification and (iii) A-ring modification. Framed within these strategies for the development of naphthoquinoidal compounds against T. cruzi. Leishmania and Cancer, reactions including copper-catalyzed azide-alkyne cycloaddition (Click Chemistry), palladium-catalysed cross couplings, C-H activation reactions, Ullmann couplings and heterocyclisations reported up to July 2019 will be discussed. The aim of derivatisation is the generation of novel molecules that can potentially inhibit cellular organelles/processes, generate Reactive Oxygen Species and increase lipophilicity to enhance penetration through the plasma membrane. Modified lapachones have emerged as promising prototypes for the development of drugs against leishmaniases, Chagas disease and Cancer.

Keywords

Anticancer activity; Chagas disease; Leishmaniasis; Naphthoquinones; Synthetic strategies; β-Lapachone.

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