SAR:s for the antiparasitic plant metabolite pulchrol. 1. The benzyl alcohol functionality.

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

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Pulchrol (1) is a natural benzochromene isolated from the roots of Bourreria pulchra, shown to possess potent antiparasitic activity towards both Leishmania and Trypanozoma species. As it is not understood which molecular features of 1 are important for the antiparasitic activity, several analogues were synthesized and assayed. The ultimate goal is to understand the structure-activity relationships (SAR:s) and create a QSAR model that can be used for the development of clinically useful antiparasitic agents. In this study, we have synthesized 25 2-methoxy-6,6-dimethyl-6Hbenzo[ c]chromen analogues of 1 and its co-metabolite pulchral (5a), by semi-synthetic procedures starting from the natural product pulchrol (1) itself. All 27 compounds, including the two natural products 1 and 5a, were subsequently assayed in vitro for antiparasitic activity against Trypanozoma cruzi, Leishmania brasiliensis and Leishmania amazoniensis. In addition, the cytotoxicity in RAW cells was assayed, and a selectivity index (SI) for each compound and each parasite was calculated. Several compounds are more potent or equi-potent compared with the positive controls Benznidazole (Trypanozoma) and Miltefosine (Leishmania). The compounds with the highest potencies as well as SI-values are esters of 1 with various carboxylic acids.

Original languageEnglish
Article number3058
JournalMolecules
Volume25
Issue number13
DOIs
StatePublished - Jul 2020

Bibliographical note

Funding Information:
Funding: This research was funded by the Swedish International Development Cooperation Agency (SIDA), including a Ph.D. scholarship for PT is gratefully acknowledged.

Publisher Copyright:
© 2020 by the authors.

Keywords

  • Benzo[c]chromenes
  • Leishmania amazoniensis
  • Leishmania brasiliensis
  • Pulchrol
  • SAR
  • Trypanozoma cruzi

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