title: Antibacterial activities and structure-activity relationships of a panel of 48 compounds from Kenyan plants against multidrug resistant phenotypes.
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.
authors.affiliation: 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.
authors.forename: Leonidah K
authors.initials: LK
authors.lastname: Omosa
authors.affiliation: Department of Chemistry, School of Physical Sciences, University of Nairobi, P. O. Box 30197-00100, Nairobi, Kenya.
authors.forename: Jacob O
authors.initials: JO
authors.lastname: Midiwo
authors.affiliation: Department of Biochemistry, Faculty of Science, University of Dschang, Dschang, Cameroon.
authors.forename: Armelle T
authors.initials: AT
authors.lastname: Mbaveng
authors.affiliation: Department of Biochemistry, Faculty of Science, University of Dschang, Dschang, Cameroon.
authors.forename: Simplice B
authors.initials: SB
authors.lastname: Tankeo
authors.affiliation: Department of Biochemistry, Faculty of Science, University of Dschang, Dschang, Cameroon.
authors.forename: Jackson A
authors.initials: JA
authors.lastname: Seukep
authors.affiliation: Department of Biochemistry, Faculty of Science, University of Dschang, Dschang, Cameroon.
authors.forename: Igor K
authors.initials: IK
authors.lastname: Voukeng
authors.affiliation: Department of Biochemistry, Faculty of Science, University of Dschang, Dschang, Cameroon.
authors.forename: Joachim K
authors.initials: JK
authors.lastname: Dzotam
authors.affiliation: Department of Chemistry, School of Physical Sciences, University of Nairobi, P. O. Box 30197-00100, Nairobi, Kenya.
authors.forename: John
authors.initials: J
authors.lastname: Isemeki
authors.affiliation: Department of Chemistry, School of Physical Sciences, University of Nairobi, P. O. Box 30197-00100, Nairobi, Kenya.
authors.forename: Solomon
authors.initials: S
authors.lastname: Derese
authors.affiliation: Department of Chemistry, School of Physical Sciences, University of Nairobi, P. O. Box 30197-00100, Nairobi, Kenya.
authors.forename: Ruth A
authors.initials: RA
authors.lastname: Omolle
authors.affiliation: Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Efferth
authors.affiliation: Department of Biochemistry, Faculty of Science, University of Dschang, Dschang, Cameroon.
authors.forename: Victor
authors.initials: V
authors.lastname: Kuete
keywords: Anthraquinones; Antibacterial activities; Benzoquinones; Chalcones; Efflux pump inhibitor; Multidrug resistance