Antibacterial activities and structure-activity relationships of a panel of 48 compounds from Kenyan plants against multidrug resistant phenotypes

Autoren

Leonidah K Omosa
Jacob O Midiwo
Armelle T Mbaveng
Simplice B Tankeo
Jackson A Seukep
Igor K Voukeng
Joachim K Dzotam
John Isemeki
Solomon Derese
Ruth A Omolle
Thomas Efferth
Victor Kuete

DOI

10.1186/s40064-016-2599-1

eISSN

2193-1801

Ausgabe der Veröffentlichung

1

Zeitschrift

SpringerPlus

Sprache

en

Artikelnummer

901

Online publication date

2016

Datum der Veröffentlichung

2016

Status

Published

Herausgeber

Springer Science and Business Media LLC

Herausgeber URL

http://dx.doi.org/10.1186/s40064-016-2599-1

Datum der Datenerfassung

2017

Titel

Antibacterial activities and structure–activity relationships of a panel of 48 compounds from Kenyan plants against multidrug resistant phenotypes

Ausgabe der Zeitschrift

5

Data source: Crossref

Abstract

In the current study forty eight compounds belonging to anthraquinones, naphthoquinones, benzoquinones, flavonoids (chalcones and polymethoxylated flavones) and diterpenoids (clerodanes and kauranes) were explored for their antimicrobial potential against a panel of sensitive and multi-drug resistant Gram-negative and Gram-positive bacteria. The minimal inhibitory concentration (MIC) determinations on the tested bacteria were conducted using modified rapid INT colorimetric assay. To evaluate the role of efflux pumps in the susceptibility of Gram-negative bacteria to the most active compounds, they were tested in the presence of phenylalanine arginine β-naphthylamide (PAβN) (at 30 µg/mL) against selected multidrug resistance (MDR) bacteria. The anthraquinone, emodin, naphthaquinone, plumbagin and the benzoquinone, rapanone were active against methicillin resistant Staphylococcus aureus (MRSA) strains of bacteria with MIC values ranging from 2 to 128 μg/mL. The structure activity relationships of benzoquinones against the MDR Gram-negative phenotype showed antibacterial activities increasing with increase in side chain length. In the chalcone series the presence of a hydroxyl group at C3' together with a methoxy group and a second hydroxyl group in meta orientation in ring B of the chalcone skeleton appeared to be necessary for minimal activities against MRSA. In most cases, the optimal potential of the active compounds were not attained as they were extruded by bacterial efflux pumps. However, the presence of the PAβN significantly increased the antibacterial activities of emodin against Gram-negative MDR E. coli AG102, 100ATet; K. pneumoniae KP55 and KP63 by >4-64 g/mL. The antibacterial activities were substantially enhanced and were higher than those of the standard drug, chloramphenicol. These data clearly demonstrate that the active compounds, having the necessary pharmacophores for antibacterial activities, including some quinones and chalcones are substrates of bacterial efflux pumps and therefore should be combined to efflux pump inhibitors in the fight against MDR bacterial infections.

Addresses

Department of Chemistry, School of Physical Sciences, University of Nairobi, P. O. Box 30197-00100, Nairobi, Kenya ; Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany.

Autoren

Leonidah K Omosa
Jacob O Midiwo
Armelle T Mbaveng
Simplice B Tankeo
Jackson A Seukep
Igor K Voukeng
Joachim K Dzotam
John Isemeki
Solomon Derese
Ruth A Omolle
Thomas Efferth
Thomas Efferth
Victor Kuete

DOI

10.1186/s40064-016-2599-1

eISSN

2193-1801

Externe Identifier

PubMed Identifier: 27386347
PubMed Central ID: PMC4923020

Funding acknowledgements

International Science Programme, Uppsala University, Sweden (ISP): KEN-02 project
International Science Programme, Uppsala University, Sweden (ISP)-: KEN-02 project
German Academic Exchange Service (DAAD):
Deutsche Forschungsgemeinschaft, Germany: Grant No. Pe 264/ 14-5
Bundesministerium für Zusammenarbeit: Grant No. Pe-254/14-6.

Open access

true

ISSN

2193-1801

Ausgabe der Veröffentlichung

1

Zeitschrift

SpringerPlus

Sprache

eng

Medium

Electronic-eCollection

Online publication date

2016

Open access status

Open Access

Paginierung

901

Datum der Veröffentlichung

2016

Status

Published

Publisher licence

CC BY

Datum der Datenerfassung

2016

Titel

Antibacterial activities and structure-activity relationships of a panel of 48 compounds from Kenyan plants against multidrug resistant phenotypes.

Sub types

research-article
Journal Article

Ausgabe der Zeitschrift

5

Files

https://springerplus.springeropen.com/track/pdf/10.1186/s40064-016-2599-1 https://europepmc.org/articles/PMC4923020?pdf=render

Data source: Europe PubMed Central

Abstract

In the current study forty eight compounds belonging to anthraquinones, naphthoquinones, benzoquinones, flavonoids (chalcones and polymethoxylated flavones) and diterpenoids (clerodanes and kauranes) were explored for their antimicrobial potential against a panel of sensitive and multi-drug resistant Gram-negative and Gram-positive bacteria. The minimal inhibitory concentration (MIC) determinations on the tested bacteria were conducted using modified rapid INT colorimetric assay. To evaluate the role of efflux pumps in the susceptibility of Gram-negative bacteria to the most active compounds, they were tested in the presence of phenylalanine arginine β-naphthylamide (PAβN) (at 30 µg/mL) against selected multidrug resistance (MDR) bacteria. The anthraquinone, emodin, naphthaquinone, plumbagin and the benzoquinone, rapanone were active against methicillin resistant Staphylococcus aureus (MRSA) strains of bacteria with MIC values ranging from 2 to 128 μg/mL. The structure activity relationships of benzoquinones against the MDR Gram-negative phenotype showed antibacterial activities increasing with increase in side chain length. In the chalcone series the presence of a hydroxyl group at C3' together with a methoxy group and a second hydroxyl group in meta orientation in ring B of the chalcone skeleton appeared to be necessary for minimal activities against MRSA. In most cases, the optimal potential of the active compounds were not attained as they were extruded by bacterial efflux pumps. However, the presence of the PAβN significantly increased the antibacterial activities of emodin against Gram-negative MDR E. coli AG102, 100ATet; K. pneumoniae KP55 and KP63 by >4-64 g/mL. The antibacterial activities were substantially enhanced and were higher than those of the standard drug, chloramphenicol. These data clearly demonstrate that the active compounds, having the necessary pharmacophores for antibacterial activities, including some quinones and chalcones are substrates of bacterial efflux pumps and therefore should be combined to efflux pump inhibitors in the fight against MDR bacterial infections.

Date of acceptance

2016

Autoren

Leonidah K Omosa
Jacob O Midiwo
Armelle T Mbaveng
Simplice B Tankeo
Jackson A Seukep
Igor K Voukeng
Joachim K Dzotam
John Isemeki
Solomon Derese
Ruth A Omolle
Thomas Efferth
Victor Kuete

Autoren-URL

https://www.ncbi.nlm.nih.gov/pubmed/27386347

DOI

10.1186/s40064-016-2599-1

Externe Identifier

PubMed Central ID: PMC4923020

ISSN

2193-1801

Ausgabe der Veröffentlichung

1

Zeitschrift

Springerplus

Schlüsselwörter

Anthraquinones
Antibacterial activities
Benzoquinones
Chalcones
Efflux pump inhibitor
Multidrug resistance

Sprache

eng

Country

Switzerland

Paginierung

901

PII

2599

Datum der Veröffentlichung

2016

Status

Published online

Datum, an dem der Datensatz öffentlich gemacht wurde

2016

Titel

Antibacterial activities and structure-activity relationships of a panel of 48 compounds from Kenyan plants against multidrug resistant phenotypes.

Sub types

Journal Article

Ausgabe der Zeitschrift

5

Data source: PubMed

Antibacterial activities and structure-activity relationships of a panel of 48 compounds from Kenyan plants against multidrug resistant phenotypes

Files

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