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

Terrazas, Paola LU ; Salamanca, Efrain ; Dávila, Marcelo ; Manner, Sophie LU ; Giménez, Alberto and Sterner, Olov LU (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
; ; ; ; and
organization
publishing date
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}},
}