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Sophie Manner

Director of studies

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Sars for the antiparasitic plant metabolite pulchrol. part 2 : B- And c-ring substituents

Author

  • Paola Terrazas
  • Sophie Manner
  • Olov Sterner
  • Marcelo Dávila
  • Alberto Giménez
  • Efrain Salamanca

Summary, in English

Neglected tropical diseases affect most of the underprivileged populations in tropical countries. Among these are chagas and leishmaniasis, present mainly in South and Central America, Africa and East Asia. Current treatments are long and have severe adverse effects, therefore there is a strong need to develop alternatives. In this study, we base our research on the plant metabolite pulchrol, a natural benzochromene which has been shown to possess antiparasitic activity against Trypanosoma and Leishmania species. In a recent study, we investigated how changes in the benzyl alcohol functionality affected the antiparasitic activity, but the importance of B- and C-ring substituents is not understood. Fifteen derivatives of pulchrol with different substituents in positions 1, 2, 3, and 6 while leaving the A-ring intact, were therefore prepared by total synthesis, assayed, and compared with pulchrol and positive controls. The generated series and parental molecule were tested in vitro for antiparasitic activity against Trypanosoma cruzi, Leishmania braziliensis, and L. amazonensis, and cytotoxicity using RAW cells. Substantial differences in the activity of the compounds synthesized were observed, of which some were more potent towards Trypanosoma cruzi than the positive control benznidazole. A general tendency is that alkyl substituents improve the potency, especially when positioned on C-2.

Department/s

  • Centre for Analysis and Synthesis

Publishing year

2020-10

Language

English

Publication/Series

Molecules

Volume

25

Issue

19

Document type

Journal article

Publisher

MDPI AG

Topic

  • Organic Chemistry

Keywords

  • Benzo[c]chromenes
  • Leishmania amazonensis
  • Leishmania braziliensis
  • Pulchrol
  • Structure-Activity Relationships (SARs)
  • Trypanosoma cruzi

Status

Published

ISBN/ISSN/Other

  • ISSN: 1420-3049