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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.

BackgroundThe Quinine tree (Rauvolfia caffra) is used as a medicinal plant among traditional communities in many countries to manage tumors and other diseases associated with oxidative stress. To validate indigenous knowledge and possibly position this herb for technology uptake and utilization, we established the level of antioxidant activity in R. caffra, and probed for the presence of associated phytochemicals.MethodsAntioxidant activity was determined on 1,1-diphenyl-2-picrylhydrazyl (DPPH) while major phytochemicals were identified by multiple tests on methanol fractions.ResultsR. caffra showed promise as a cure, with antioxidant activity comparable to the commercially used drug quercetin (R. caffra = 79.7% ±1.9; quercetin = 82.6% ± 2.0). However, we found two phytochemicals with possible antagonistic effect: co-occurrence of alkaloids and saponins significantly reduced antioxidant activity (alkaloids only = 63%; alkaloids plus saponins = 15%; steroids, terpenoids and cardiac glycosides = 82%), thus alkaloids and saponins should be exclusive to each other in drug formulations.ConclusionsAntagonistic relationship among phytochemicals would affect the efficacy of crude extracts as used in traditional medicine. Unlike in herbal medicine, use of modern biotechnology in extraction, purification and design of optimal combinations will ensure efficient drug formulations with optimum bioactivity and minimum toxicity. Metabolic pathway engineering under a controlled environment may optimize availability of desired compounds.

BackgroundCancer is a major public health concern globally and chemotherapy remains the principal mode of the treatment of various malignant diseases.MethodsThis study was designed to investigate the cytotoxicity of 14 naturally occurring quinones including; 3 anthraquinones, 1 naphthoquinone and 10 benzoquinones against 6 human carcinoma cell lines and normal CRL2120 fibroblasts. The neutral red uptake (NR) assay was used to evaluate the cytotoxicity of the compounds, whilst caspase-Glo assay was used to detect caspases activation. Cell cycle and mitochondrial membrane potential (MMP) were all analyzed via flow cytometry meanwhile levels of reactive oxygen species (ROS) were measured by spectrophotometry.ResultsAnthraquinone: emodin (2), naphthoquinone: plumbagin (4), and benzoquinones: rapanone (9), 2,5-dihydroxy-3-pentadecyl-2,5-cyclohexadiene-1,4-dione (10), 5-O-methylembelin (11), 1,2,4,5-tetraacetate-3-methyl-6-(14-nonadecenyl)-cyclohexadi-2,5-diene (13), as well as doxorubicin displayed interesting activities with IC50 values below 100 μM in the six tested cancer cell lines. The IC50 values ranged from 37.57 μM (towards breast adenocarcinoma MCF-7 cells) to 99.31 μM (towards small cell lung cancer A549 cells) for 2, from 0.06 μM (MCF-7 cells) to 1.14 μM (A549 cells) for 4, from 2.27 μM (mesothelioma SPC212 cells) to 46.62 μM (colorectal adenocarcinoma DLD-1 cells) for 9, from 8.39 μM (SPC212 cells) to 48.35 μM (hepatocarinoma HepG2 cells) for 10, from 22.57 μM (MCF-7 cells) to 61.28 μM (HepG2 cells) for 11, from 9.25 μM (MCF-7 cells) to 47.53 μM (A549 cells) for 13, and from 0.07 μM (SPC212 cells) to 1.01 μM (A549 cells) for doxorubicin. Compounds 4 and 9 induced apoptosis in MCF-7 cells mediated by increased ROS production and MMP loss, respectively.ConclusionThe tested natural products and mostly 2, 4, 9, 10, 11 and 13 are potential cytotoxic compounds that deserve more investigations towards developing novel antiproliferative drugs against human carcinoma.