Sars for the antiparasitic plant metabolite pulchrol. part 2 : B- And c-ring substituents
(2020) In Molecules 25(19).- Abstract
Neglected tropical diseases affect most of the underprivileged populations in tropical countries. Among these are chagas and leishmaniasis, present mainly in South and Central America, Africa and East Asia. Current treatments are long and have severe adverse effects, therefore there is a strong need to develop alternatives. In this study, we base our research on the plant metabolite pulchrol, a natural benzochromene which has been shown to possess antiparasitic activity against Trypanosoma and Leishmania species. In a recent study, we investigated how changes in the benzyl alcohol functionality affected the antiparasitic activity, but the importance of B- and C-ring substituents is not understood. Fifteen derivatives of pulchrol with... (More)
Neglected tropical diseases affect most of the underprivileged populations in tropical countries. Among these are chagas and leishmaniasis, present mainly in South and Central America, Africa and East Asia. Current treatments are long and have severe adverse effects, therefore there is a strong need to develop alternatives. In this study, we base our research on the plant metabolite pulchrol, a natural benzochromene which has been shown to possess antiparasitic activity against Trypanosoma and Leishmania species. In a recent study, we investigated how changes in the benzyl alcohol functionality affected the antiparasitic activity, but the importance of B- and C-ring substituents is not understood. Fifteen derivatives of pulchrol with different substituents in positions 1, 2, 3, and 6 while leaving the A-ring intact, were therefore prepared by total synthesis, assayed, and compared with pulchrol and positive controls. The generated series and parental molecule were tested in vitro for antiparasitic activity against Trypanosoma cruzi, Leishmania braziliensis, and L. amazonensis, and cytotoxicity using RAW cells. Substantial differences in the activity of the compounds synthesized were observed, of which some were more potent towards Trypanosoma cruzi than the positive control benznidazole. A general tendency is that alkyl substituents improve the potency, especially when positioned on C-2.
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- author
- Terrazas, Paola LU ; Manner, Sophie LU ; Sterner, Olov LU ; Dávila, Marcelo ; Giménez, Alberto and Salamanca, Efrain
- organization
- publishing date
- 2020-10
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Benzo[c]chromenes, Leishmania amazonensis, Leishmania braziliensis, Pulchrol, Structure-Activity Relationships (SARs), Trypanosoma cruzi
- in
- Molecules
- volume
- 25
- issue
- 19
- article number
- 4510
- publisher
- MDPI AG
- external identifiers
-
- pmid:33019678
- scopus:85092559250
- ISSN
- 1420-3049
- DOI
- 10.3390/molecules25194510
- language
- English
- LU publication?
- yes
- id
- db32be42-f63f-40c5-91e8-2ffc1eaa49a1
- date added to LUP
- 2020-11-09 10:21:54
- date last changed
- 2024-10-03 12:18:07
@article{db32be42-f63f-40c5-91e8-2ffc1eaa49a1,
abstract = {{<p>Neglected tropical diseases affect most of the underprivileged populations in tropical countries. Among these are chagas and leishmaniasis, present mainly in South and Central America, Africa and East Asia. Current treatments are long and have severe adverse effects, therefore there is a strong need to develop alternatives. In this study, we base our research on the plant metabolite pulchrol, a natural benzochromene which has been shown to possess antiparasitic activity against Trypanosoma and Leishmania species. In a recent study, we investigated how changes in the benzyl alcohol functionality affected the antiparasitic activity, but the importance of B- and C-ring substituents is not understood. Fifteen derivatives of pulchrol with different substituents in positions 1, 2, 3, and 6 while leaving the A-ring intact, were therefore prepared by total synthesis, assayed, and compared with pulchrol and positive controls. The generated series and parental molecule were tested in vitro for antiparasitic activity against Trypanosoma cruzi, Leishmania braziliensis, and L. amazonensis, and cytotoxicity using RAW cells. Substantial differences in the activity of the compounds synthesized were observed, of which some were more potent towards Trypanosoma cruzi than the positive control benznidazole. A general tendency is that alkyl substituents improve the potency, especially when positioned on C-2.</p>}},
author = {{Terrazas, Paola and Manner, Sophie and Sterner, Olov and Dávila, Marcelo and Giménez, Alberto and Salamanca, Efrain}},
issn = {{1420-3049}},
keywords = {{Benzo[c]chromenes; Leishmania amazonensis; Leishmania braziliensis; Pulchrol; Structure-Activity Relationships (SARs); Trypanosoma cruzi}},
language = {{eng}},
number = {{19}},
publisher = {{MDPI AG}},
series = {{Molecules}},
title = {{Sars for the antiparasitic plant metabolite pulchrol. part 2 : B- And c-ring substituents}},
url = {{http://dx.doi.org/10.3390/molecules25194510}},
doi = {{10.3390/molecules25194510}},
volume = {{25}},
year = {{2020}},
}