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.

Cytotoxicity of Plumbagin, Rapanone and 12 other naturally occurring Quinones from Kenyan Flora towards human carcinoma cells

“…The fourteen investigated compounds included three anthraquinones; chrysophanol C 15 H 10 O 4 ( 1 ; m / z : 254.0579), emodin C 15 H 10 O 5 ( 2 ; m / z : 270.0528), 3,6,8-trihydroxy-1-methylanthraquinone-2-carboxylic acid methyl ester C 17 H 12 O 7 ( 3 ; m / z : 328.0583), one naphthaquinone; 5-hydroxy-2-methyl-1,4-naphthalenedione or plumbagin C 11 H 8 O 3 ( 4 ; m / z : 188.0473), and benzoquinones; 2,5-dihydroxy-3-ethyl-2,5-cyclohexadiene-1,4-dione C 8 H 8 O 4 ( 5 ; m / z : 168.0423), 2,5-dihydroxy-3-propyl-2,5-cyclohexadiene-1,4-dione C 9 H 10 O 4 ( 6 ; m / z : 182.0579), 2,5-dihydroxy-3-butyl-2,5-cyclohexadiene-1,4-dione C 10 H 12 O 4 ( 7 ; m / z : 196.0736), 2,5-dihydroxy-3-heptyl-2,5-cyclohexadiene-1,4-dione C 13 H 18 O 4 ( 8 ; m / z : 238.1205), 2,5-dihydroxy-3-tridecyl-2,5-cyclohexadiene-1,4-dione or rapanone C 19 H 30 O 4 ( 9 ; m / z : 332.4450), 2,5-dihydroxy-3-pentadecyl-2,5-cyclohexadiene-1,4-dione C 21 H 34 O 4 ( 10 ; m / z : 350.2457), 2-hydroxy-5-methoxy-3-undecyl-1,4-benzoquinone, 5- O -methylembelin C 18 H 28 O 4 ( 11 ; m / z : 308.1988), 2,5 dimethoxy-6-(14-nonadecenyl)-1,4-benzoquinone C 27 H 44 O 4 ( 12 ; m / z : 432.3240), 1,2,4,5-tetraacetate-3-methyl-6-(14-nonadecenyl)-cyclohexadi-2,5-diene C 34 H 54 O 8 ( 13 ; m / z : 590.3819), ardisiaquinone B C 30 H 40 O 8 ( 14 ; m / z : 528.2723) [10]. These compounds are available in the Chemical bank of the Department of Chemistry, University of Nairobi, Kenya.…”

“…1) used in this study were obtained from the chemical bank of the natural products research laboratory of the Chemistry Department, University of Nairobi, Kenya. Their isolation and identification were previously reported from the following plants: Rumex dentatus , R. abyssinicus , R. usambarensis , R. bequaertii , R. ruwenzoriensis , R. crispus ; Plumbago zeylanica , Myrsine Africana , Maesa lanceolata , Rapanea melanphloes , Aloe saponaria [10]. They include anthraquinones: chrysophanol ( 1 ), emodin ( 2 ), 3,6,8-trihydroxy-1-methylanthraquinone-2-carboxylic acid methyl ester ( 3 ), a naphthaquinone: 5-hydroxy-2-methyl-1,4-naphthalenedione or plumbagin ( 4 ), benzoquinones; 2,5-dihydroxy-3-ethyl-2,5-cyclohexadiene-1,4-dione ( 5 ), 2,5-dihydroxy-3-propyl-2,5-cyclohexadiene-1,4-dione ( 6 ), 2,5-dihydroxy-3-butyl-2,5-cyclohexadiene-1,4-dione ( 7 ), 2,5-dihydroxy-3-heptyl-2,5-cyclohexadiene-1,4-dione ( 8 ), 2,5-dihydroxy-3-tridecyl-2,5-cyclohexadiene-1,4-dione or rapanone ( 9 ), 2,5-dihydroxy-3-pentadecyl-2,5-cyclohexadiene-1,4-dione ( 10 ), 2-hydroxy-5-methoxy-3-undecyl-1,4-benzoquinone or 5- O -methylembelin ( 11 ), 2,5 dimethoxy-6-(14-nonadecenyl)-1,4-benzoquinone ( 12 ), 1,2,4,5-tetraacetate-3-methyl-6-(14-nonadecenyl)-cyclohexadi-2,5-diene ( 13 ) and ardisiaquinone B ( 14 ) [10].…”

Plumbagin, a natural naphthoquinone, inhibits the growth of esophageal squamous cell carcinoma cells through inactivation of STAT3

“…1A) is a natural naphthoquinone that is widely distributed in the family of Plumbaginaceae. Plumbagin exhibits multiple biological properties, including antibacterial (5), antimalarial (6), anti-inflammatory (7), and antitumor (8) activities. It has been documented that plumbagin inhibits the invasion of breast cancer cells by inactivating signal transducer and activator of transcription 3 (STAT3) signaling (8).…”

Crystal structure of 2-(3,5-dimethoxyphenylamino)-3-chloronaphthalene-1,4-dione

“…Dyes are also very important materials [5,6] that most quinones found themselves in [7]. They also display reach biological activities [8] like antifungal [9], antibacterial [10], anticancer [11], antimalarial [12], hypoglycemic [13], analgesic [14], anti-inflammatory [15], and HIV inhibitory [16]. The redox polymers based on quinones owing to their redox ability have been investigated to develop batteries and biosensors [17,18].…”