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
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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-6
H-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.
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