Sophie Manner
Studierektor
SAR:s for the Antiparasitic Plant Metabolite Pulchrol. 1. The Benzyl Alcohol Functionality
Författare
Summary, in English
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-6H-benzo[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.
Avdelning/ar
- Centrum för analys och syntes
Publiceringsår
2020-07-04
Språk
Engelska
Publikation/Tidskrift/Serie
Molecules (Basel, Switzerland)
Volym
25
Issue
13
Dokumenttyp
Artikel i tidskrift
Förlag
MDPI AG
Ämne
- Biochemistry and Molecular Biology
Nyckelord
- benzo[c]chromenes
- Leishmania amazoniensis
- Leishmania brasiliensis
- pulchrol
- SAR.
- Trypanozoma cruzi
Status
Published
ISBN/ISSN/Övrigt
- ISSN: 1420-3049