Methoxychalcones: Effect of methoxyl group on the antifungal, antibac-terial and antiproliferative activities
Autor(a) principal: | |
---|---|
Data de Publicação: | 2020 |
Outros Autores: | , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.2174/1573406415666190724145158 http://hdl.handle.net/11449/202015 |
Resumo: | Background: Chalcones substituted by methoxyl groups have presented a broad spec-trum of bioactivities, including antifungal, antibacterial and antiproliferative effects. However, a clear and unambiguous investigation about the relevance of this substituent on the chalcone framework has not been described. Objective: The purpose of this work is to assess the antibacterial, antifungal and antiproliferative activities of the two series of seventeen synthesized regioisomeric methoxychalcones. Series I and II were constituted by chalcones substituted by methoxyl groups on rings A (5–12) and B (13–21), respectively. In addition, the library of methoxychalcones was submitted to in silico drug-likeness and pharmacokinetics properties predictions. Methods: Methoxychalcones were synthesized and their structures were confirmed by NMR spectral data analyses. Evaluations of antimicrobial activity were performed against five species of Candida, two Gram-negative and five Gram-positive species. For antiproliferative activity, methoxychalcones were evaluated against four human tumorigenic cell lines, as well as human non-tumorigenic keratinocytes. Drug-likeness and pharmacokinetics properties were predicted using Molinspiration and PreADMET toolkits. Results: In general, chalcones of series I are the most potent antifungal, antibacterial and antipro-liferative agents. 3’, 4’, 5’-Trimethoxychalcone (12) demonstrated potent antifungal activity against Candida krusei (MIC = 3.9 µg/mL), eight times more potent than fluconazole (reference antifungal drug). 3’-Methoxychalcone (6) displayed anti-Pseudomonas activity (MIC = 7.8 µg/mL). 2’,5’-Dimethoxychalcone (9) displayed potent antiproliferative effect against C-33A (cervix), A-431 (skin) and MCF-7 (breast), with IC50 values ranging from 7.7 to 9.2 µM. Its potency was superior to curcumin (reference antiproliferative compound), which exhibited IC50 values ranging from 10.4 to 19.0 µM. Conclusion: Our studies corroborated the relevance of methoxychalcones as antifungal, antibacte-rial and antiproliferative agents. In addition, we elucidated influence of the position and number of methoxyl groups toward bioactivity. In silico predictions indicated good drug-likeness and phar-macokinetics properties to the library of methoxychalcones. |
id |
UNSP_adbb31e1135a558453259575d8d10ce8 |
---|---|
oai_identifier_str |
oai:repositorio.unesp.br:11449/202015 |
network_acronym_str |
UNSP |
network_name_str |
Repositório Institucional da UNESP |
repository_id_str |
2946 |
spelling |
Methoxychalcones: Effect of methoxyl group on the antifungal, antibac-terial and antiproliferative activitiesAntibacterialAntifungalAntiproliferativeChalconeDrug-likenessMethoxylBackground: Chalcones substituted by methoxyl groups have presented a broad spec-trum of bioactivities, including antifungal, antibacterial and antiproliferative effects. However, a clear and unambiguous investigation about the relevance of this substituent on the chalcone framework has not been described. Objective: The purpose of this work is to assess the antibacterial, antifungal and antiproliferative activities of the two series of seventeen synthesized regioisomeric methoxychalcones. Series I and II were constituted by chalcones substituted by methoxyl groups on rings A (5–12) and B (13–21), respectively. In addition, the library of methoxychalcones was submitted to in silico drug-likeness and pharmacokinetics properties predictions. Methods: Methoxychalcones were synthesized and their structures were confirmed by NMR spectral data analyses. Evaluations of antimicrobial activity were performed against five species of Candida, two Gram-negative and five Gram-positive species. For antiproliferative activity, methoxychalcones were evaluated against four human tumorigenic cell lines, as well as human non-tumorigenic keratinocytes. Drug-likeness and pharmacokinetics properties were predicted using Molinspiration and PreADMET toolkits. Results: In general, chalcones of series I are the most potent antifungal, antibacterial and antipro-liferative agents. 3’, 4’, 5’-Trimethoxychalcone (12) demonstrated potent antifungal activity against Candida krusei (MIC = 3.9 µg/mL), eight times more potent than fluconazole (reference antifungal drug). 3’-Methoxychalcone (6) displayed anti-Pseudomonas activity (MIC = 7.8 µg/mL). 2’,5’-Dimethoxychalcone (9) displayed potent antiproliferative effect against C-33A (cervix), A-431 (skin) and MCF-7 (breast), with IC50 values ranging from 7.7 to 9.2 µM. Its potency was superior to curcumin (reference antiproliferative compound), which exhibited IC50 values ranging from 10.4 to 19.0 µM. Conclusion: Our studies corroborated the relevance of methoxychalcones as antifungal, antibacte-rial and antiproliferative agents. In addition, we elucidated influence of the position and number of methoxyl groups toward bioactivity. In silico predictions indicated good drug-likeness and phar-macokinetics properties to the library of methoxychalcones.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Department of Chemistry and Environmental Sciences Institute of Biosciences Humanities and Exact Sciences São Paulo State University (Unesp)Department of Biology Institute of Bio-sciences Humanities and Exact Sciences São Paulo State University (Unesp)Department of Physiological Sciences Piracicaba Dental School University of Campinas (Unicamp)Department of Chemistry and Environmental Sciences Institute of Biosciences Humanities and Exact Sciences São Paulo State University (Unesp)Department of Biology Institute of Bio-sciences Humanities and Exact Sciences São Paulo State University (Unesp)CAPES: 001FAPESP: 2009/53989-4FAPESP: 2014/18330-0FAPESP: 2014/18577-5FAPESP: 2014/50926-0FAPESP: 2016/08084-7FAPESP: 2017/09245-7FAPESP: 2018/ 15083-2CNPq: 309957/2019-2 306251/ 2016-7CNPq: 429322/2018-6CNPq: 465637/2014-0CNPq: 471129/2013-5Universidade Estadual Paulista (Unesp)Universidade Estadual de Campinas (UNICAMP)Marques, Beatriz C. [UNESP]Santos, Mariana B. [UNESP]Anselmo, Daiane B. [UNESP]Monteiro, Diego A. [UNESP]Gomes, Eleni [UNESP]Saiki, Marilia F. C. [UNESP]Rahal, Paula [UNESP]Rosalen, Pedro L.Sardi, Janaina C. O.Regasini, Luis O. [UNESP]2020-12-12T02:47:42Z2020-12-12T02:47:42Z2020-01-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article881-891http://dx.doi.org/10.2174/1573406415666190724145158Medicinal Chemistry, v. 16, n. 7, p. 881-891, 2020.1875-66381573-4064http://hdl.handle.net/11449/20201510.2174/15734064156661907241451582-s2.0-8508939278179910823626712120000-0001-5693-6148Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengMedicinal Chemistryinfo:eu-repo/semantics/openAccess2021-10-23T10:11:29Zoai:repositorio.unesp.br:11449/202015Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462021-10-23T10:11:29Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Methoxychalcones: Effect of methoxyl group on the antifungal, antibac-terial and antiproliferative activities |
title |
Methoxychalcones: Effect of methoxyl group on the antifungal, antibac-terial and antiproliferative activities |
spellingShingle |
Methoxychalcones: Effect of methoxyl group on the antifungal, antibac-terial and antiproliferative activities Marques, Beatriz C. [UNESP] Antibacterial Antifungal Antiproliferative Chalcone Drug-likeness Methoxyl |
title_short |
Methoxychalcones: Effect of methoxyl group on the antifungal, antibac-terial and antiproliferative activities |
title_full |
Methoxychalcones: Effect of methoxyl group on the antifungal, antibac-terial and antiproliferative activities |
title_fullStr |
Methoxychalcones: Effect of methoxyl group on the antifungal, antibac-terial and antiproliferative activities |
title_full_unstemmed |
Methoxychalcones: Effect of methoxyl group on the antifungal, antibac-terial and antiproliferative activities |
title_sort |
Methoxychalcones: Effect of methoxyl group on the antifungal, antibac-terial and antiproliferative activities |
author |
Marques, Beatriz C. [UNESP] |
author_facet |
Marques, Beatriz C. [UNESP] Santos, Mariana B. [UNESP] Anselmo, Daiane B. [UNESP] Monteiro, Diego A. [UNESP] Gomes, Eleni [UNESP] Saiki, Marilia F. C. [UNESP] Rahal, Paula [UNESP] Rosalen, Pedro L. Sardi, Janaina C. O. Regasini, Luis O. [UNESP] |
author_role |
author |
author2 |
Santos, Mariana B. [UNESP] Anselmo, Daiane B. [UNESP] Monteiro, Diego A. [UNESP] Gomes, Eleni [UNESP] Saiki, Marilia F. C. [UNESP] Rahal, Paula [UNESP] Rosalen, Pedro L. Sardi, Janaina C. O. Regasini, Luis O. [UNESP] |
author2_role |
author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (Unesp) Universidade Estadual de Campinas (UNICAMP) |
dc.contributor.author.fl_str_mv |
Marques, Beatriz C. [UNESP] Santos, Mariana B. [UNESP] Anselmo, Daiane B. [UNESP] Monteiro, Diego A. [UNESP] Gomes, Eleni [UNESP] Saiki, Marilia F. C. [UNESP] Rahal, Paula [UNESP] Rosalen, Pedro L. Sardi, Janaina C. O. Regasini, Luis O. [UNESP] |
dc.subject.por.fl_str_mv |
Antibacterial Antifungal Antiproliferative Chalcone Drug-likeness Methoxyl |
topic |
Antibacterial Antifungal Antiproliferative Chalcone Drug-likeness Methoxyl |
description |
Background: Chalcones substituted by methoxyl groups have presented a broad spec-trum of bioactivities, including antifungal, antibacterial and antiproliferative effects. However, a clear and unambiguous investigation about the relevance of this substituent on the chalcone framework has not been described. Objective: The purpose of this work is to assess the antibacterial, antifungal and antiproliferative activities of the two series of seventeen synthesized regioisomeric methoxychalcones. Series I and II were constituted by chalcones substituted by methoxyl groups on rings A (5–12) and B (13–21), respectively. In addition, the library of methoxychalcones was submitted to in silico drug-likeness and pharmacokinetics properties predictions. Methods: Methoxychalcones were synthesized and their structures were confirmed by NMR spectral data analyses. Evaluations of antimicrobial activity were performed against five species of Candida, two Gram-negative and five Gram-positive species. For antiproliferative activity, methoxychalcones were evaluated against four human tumorigenic cell lines, as well as human non-tumorigenic keratinocytes. Drug-likeness and pharmacokinetics properties were predicted using Molinspiration and PreADMET toolkits. Results: In general, chalcones of series I are the most potent antifungal, antibacterial and antipro-liferative agents. 3’, 4’, 5’-Trimethoxychalcone (12) demonstrated potent antifungal activity against Candida krusei (MIC = 3.9 µg/mL), eight times more potent than fluconazole (reference antifungal drug). 3’-Methoxychalcone (6) displayed anti-Pseudomonas activity (MIC = 7.8 µg/mL). 2’,5’-Dimethoxychalcone (9) displayed potent antiproliferative effect against C-33A (cervix), A-431 (skin) and MCF-7 (breast), with IC50 values ranging from 7.7 to 9.2 µM. Its potency was superior to curcumin (reference antiproliferative compound), which exhibited IC50 values ranging from 10.4 to 19.0 µM. Conclusion: Our studies corroborated the relevance of methoxychalcones as antifungal, antibacte-rial and antiproliferative agents. In addition, we elucidated influence of the position and number of methoxyl groups toward bioactivity. In silico predictions indicated good drug-likeness and phar-macokinetics properties to the library of methoxychalcones. |
publishDate |
2020 |
dc.date.none.fl_str_mv |
2020-12-12T02:47:42Z 2020-12-12T02:47:42Z 2020-01-01 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.2174/1573406415666190724145158 Medicinal Chemistry, v. 16, n. 7, p. 881-891, 2020. 1875-6638 1573-4064 http://hdl.handle.net/11449/202015 10.2174/1573406415666190724145158 2-s2.0-85089392781 7991082362671212 0000-0001-5693-6148 |
url |
http://dx.doi.org/10.2174/1573406415666190724145158 http://hdl.handle.net/11449/202015 |
identifier_str_mv |
Medicinal Chemistry, v. 16, n. 7, p. 881-891, 2020. 1875-6638 1573-4064 10.2174/1573406415666190724145158 2-s2.0-85089392781 7991082362671212 0000-0001-5693-6148 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Medicinal Chemistry |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
881-891 |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
_version_ |
1799965486119649280 |