Cargando…

Quantifying synergy in the bioassay-guided fractionation of natural product extracts

Mixtures of drugs often have greater therapeutic value than any of their constituent drugs alone, and such combination therapies are widely used to treat diseases such as cancer, malaria, and viral infections. However, developing useful drug mixtures is challenging due to complex interactions betwee...

Descripción completa

Detalles Bibliográficos
Autores principales: Dettweiler, Micah, Marquez, Lewis, Bao, Max, Quave, Cassandra L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7428089/
https://www.ncbi.nlm.nih.gov/pubmed/32797045
http://dx.doi.org/10.1371/journal.pone.0235723
_version_ 1783571004805611520
author Dettweiler, Micah
Marquez, Lewis
Bao, Max
Quave, Cassandra L.
author_facet Dettweiler, Micah
Marquez, Lewis
Bao, Max
Quave, Cassandra L.
author_sort Dettweiler, Micah
collection PubMed
description Mixtures of drugs often have greater therapeutic value than any of their constituent drugs alone, and such combination therapies are widely used to treat diseases such as cancer, malaria, and viral infections. However, developing useful drug mixtures is challenging due to complex interactions between drugs. Natural substances can be fruitful sources of useful drug mixtures because secondary metabolites produced by living organisms do not often act in isolation in vivo. In order to facilitate the study of interactions within natural substances, a new analytical method to quantify interactions using data generated in the process of bioassay-guided fractionation is presented here: the extract fractional inhibitory concentration index (EFICI). The EFICI method uses the framework of Loewe additivity to calculate fractional inhibitory concentration values by which interactions can be determined for any combination of fractions that make up a parent extract. The EFICI method was applied to data on the bioassay-guided fractionation of Lechea mucronata and Schinus terebinthifolia for growth inhibition of the pathogenic bacterium Acinetobacter baumannii. The L. mucronata extract contained synergistic interactions (EFICI = 0.4181) and the S. terebinthifolia extract was non-interactive overall (EFICI = 0.9129). Quantifying interactions in the bioassay-guided fractionation of natural substances does not require additional experiments and can be useful to guide the experimental process and to support the development of standardized extracts as botanical drugs.
format Online
Article
Text
id pubmed-7428089
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-74280892020-08-20 Quantifying synergy in the bioassay-guided fractionation of natural product extracts Dettweiler, Micah Marquez, Lewis Bao, Max Quave, Cassandra L. PLoS One Research Article Mixtures of drugs often have greater therapeutic value than any of their constituent drugs alone, and such combination therapies are widely used to treat diseases such as cancer, malaria, and viral infections. However, developing useful drug mixtures is challenging due to complex interactions between drugs. Natural substances can be fruitful sources of useful drug mixtures because secondary metabolites produced by living organisms do not often act in isolation in vivo. In order to facilitate the study of interactions within natural substances, a new analytical method to quantify interactions using data generated in the process of bioassay-guided fractionation is presented here: the extract fractional inhibitory concentration index (EFICI). The EFICI method uses the framework of Loewe additivity to calculate fractional inhibitory concentration values by which interactions can be determined for any combination of fractions that make up a parent extract. The EFICI method was applied to data on the bioassay-guided fractionation of Lechea mucronata and Schinus terebinthifolia for growth inhibition of the pathogenic bacterium Acinetobacter baumannii. The L. mucronata extract contained synergistic interactions (EFICI = 0.4181) and the S. terebinthifolia extract was non-interactive overall (EFICI = 0.9129). Quantifying interactions in the bioassay-guided fractionation of natural substances does not require additional experiments and can be useful to guide the experimental process and to support the development of standardized extracts as botanical drugs. Public Library of Science 2020-08-14 /pmc/articles/PMC7428089/ /pubmed/32797045 http://dx.doi.org/10.1371/journal.pone.0235723 Text en © 2020 Dettweiler et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Dettweiler, Micah
Marquez, Lewis
Bao, Max
Quave, Cassandra L.
Quantifying synergy in the bioassay-guided fractionation of natural product extracts
title Quantifying synergy in the bioassay-guided fractionation of natural product extracts
title_full Quantifying synergy in the bioassay-guided fractionation of natural product extracts
title_fullStr Quantifying synergy in the bioassay-guided fractionation of natural product extracts
title_full_unstemmed Quantifying synergy in the bioassay-guided fractionation of natural product extracts
title_short Quantifying synergy in the bioassay-guided fractionation of natural product extracts
title_sort quantifying synergy in the bioassay-guided fractionation of natural product extracts
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7428089/
https://www.ncbi.nlm.nih.gov/pubmed/32797045
http://dx.doi.org/10.1371/journal.pone.0235723
work_keys_str_mv AT dettweilermicah quantifyingsynergyinthebioassayguidedfractionationofnaturalproductextracts
AT marquezlewis quantifyingsynergyinthebioassayguidedfractionationofnaturalproductextracts
AT baomax quantifyingsynergyinthebioassayguidedfractionationofnaturalproductextracts
AT quavecassandral quantifyingsynergyinthebioassayguidedfractionationofnaturalproductextracts