SAR:s for the Antiparasitic Plant Metabolite Pulchrol. 1. The Benzyl Alcohol Functionality
(2020) In Molecules (Basel, Switzerland) 25(13).- 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-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... (More)
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.
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- author
- Terrazas, Paola LU ; Salamanca, Efrain ; Dávila, Marcelo ; Manner, Sophie LU ; Giménez, Alberto and Sterner, Olov LU
- organization
- publishing date
- 2020-07-04
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- benzo[c]chromenes, Leishmania amazoniensis, Leishmania brasiliensis, pulchrol, SAR., Trypanozoma cruzi
- in
- Molecules (Basel, Switzerland)
- volume
- 25
- issue
- 13
- article number
- 3058
- publisher
- MDPI AG
- external identifiers
-
- scopus:85087668376
- pmid:32635469
- ISSN
- 1420-3049
- DOI
- 10.3390/molecules25133058
- language
- English
- LU publication?
- yes
- id
- fbb51695-c54c-4e7f-999b-2406f567aa22
- date added to LUP
- 2020-07-22 08:56:02
- date last changed
- 2024-05-29 17:05:08
@article{fbb51695-c54c-4e7f-999b-2406f567aa22, abstract = {{<p>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.</p>}}, author = {{Terrazas, Paola and Salamanca, Efrain and Dávila, Marcelo and Manner, Sophie and Giménez, Alberto and Sterner, Olov}}, issn = {{1420-3049}}, keywords = {{benzo[c]chromenes; Leishmania amazoniensis; Leishmania brasiliensis; pulchrol; SAR.; Trypanozoma cruzi}}, language = {{eng}}, month = {{07}}, number = {{13}}, publisher = {{MDPI AG}}, series = {{Molecules (Basel, Switzerland)}}, title = {{SAR:s for the Antiparasitic Plant Metabolite Pulchrol. 1. The Benzyl Alcohol Functionality}}, url = {{http://dx.doi.org/10.3390/molecules25133058}}, doi = {{10.3390/molecules25133058}}, volume = {{25}}, year = {{2020}}, }