The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

Default user image.

Sophie Manner

Director of studies

Default user image.

SARs for the antiparasitic plant metabolite pulchrol. : 3. Combinations of new substituents in A/B-rings and A/C-rings

Author

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

Summary, in English

The natural products pulchrol and pulchral, isolated from the roots of the Mexican plant Bourreria pulchra, have previously been shown to possess an antiparasitic activity toward Trypanosoma cruzi, Leishmania braziliensis and L. amazonensis, protozoa responsible for the Chagas disease and leishmaniasis. These infections have been classified as neglected diseases, and still require the development of safer and more efficient alternatives to their current treatments. Recent SAR stud-ies, based on the pulchrol scaffold, showed which effect the exchanges of its substituents have on the antileishmanial and antitrypanosomal activity. Many of the analogues prepared were shown to be more potent in vitro than pulchrol and the current drugs used to treat Leishmaniasis and the Chagas disease (Miltefosine and Benznidazole respectively). Moreover, indications of some of the possible interactions that may take place in the binding sites were also identified. In this study, 12 analogues with modifications at two or three different positions in two of the three rings were prepared by synthetic and semi-synthetic procedures. The molecules were assayed in vitro to-ward T. cruzi epimastigotes, L. braziliensis promastigotes and L. amazonensis promastigotes. Some compounds had higher antiparasitic activity than the parent compound pulchrol, and in some cases even Benznidazole and Miltefosine. The best combinations in this subset are with carbonyl functionalities in the A-ring and isopropyl groups in the C-ring, as well as with alkyl substituents in both the A- and C-rings combined with a hydroxyl group in position 1 (C-ring). The latter corresponds to cannabinol, which was shown to be potent toward all parasites.

Department/s

  • Centre for Analysis and Synthesis

Publishing year

2021-07-01

Language

English

Publication/Series

Molecules

Volume

26

Issue

13

Document type

Journal article

Publisher

MDPI AG

Topic

  • Organic Chemistry
  • Biochemistry and Molecular Biology

Keywords

  • Trypanosoma cruzi
  • Leishmania braziliensis
  • Leishmania amazonensis
  • pulchrol
  • pulchral
  • cannabinol
  • SARs

Status

Published

ISBN/ISSN/Other

  • ISSN: 1420-3049