SAR:s for the Antiparasitic Plant Metabolite Pulchrol. 1. The Benzyl Alcohol Functionality

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.

• Author: Paola Terrazas; Efrain Salamanca; Marcelo Dávila; Sophie Manner; Alberto Giménez; Olov Sterner
• Department/s: Centre for Analysis and Synthesis
• Publishing year: 2020-07-04
• Language: English
• Publication/Series: Molecules (Basel, Switzerland)
• Volume: 25
• Issue: 13
• Links: http://dx.doi.org/10.3390/molecules25133058
• Document type: Journal article
• Publisher: MDPI AG
• Topic: Biochemistry and Molecular Biology
• Keywords: benzo[c]chromenes; Leishmania amazoniensis; Leishmania brasiliensis; pulchrol; SAR.; Trypanozoma cruzi
• Status: Published
• ISBN/ISSN/Other: ISSN: 1420-3049