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Sophie Manner

Studierektor

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

Författare

  • 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.

Avdelning/ar

  • Centrum för analys och syntes

Publiceringsår

2021-07-01

Språk

Engelska

Publikation/Tidskrift/Serie

Molecules

Volym

26

Issue

13

Dokumenttyp

Artikel i tidskrift

Förlag

MDPI AG

Ämne

  • Organic Chemistry
  • Biochemistry and Molecular Biology

Nyckelord

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

Status

Published

ISBN/ISSN/Övrigt

  • ISSN: 1420-3049