Kenneth O. Eyong

Antibacterial activity of some natural products against bacteria expressing a multidrug-resistant phenotype

The present study assessed the antimicrobial activities of various natural products belonging to the terpenoids, alkaloids and phenolics against a collection of Gram-negative multidrug-resistant (MDR) bacteria. The results demonstrated that most of the compounds were extruded by bacterial efflux pumps. In the presence of the efflux pump inhibitor phenylalanine arginine β-naphthylamide (PAβN), the activities of laurentixanthone B (xanthone), plumbagin (naphthoquinone), 4-hydroxylonchocarpin (flavonoid) and MAB3 (coumarin) increased significantly against all studied MDR bacteria. Laurentixanthone B, 4-hydroxylonchocarpin and MAB3 contained the same pharmacophoric moiety as plumbagin. This study indicates that the AcrAB-TolC (Enterobacteriaceae) and MexAB-OprM (Pseudomonas aeruginosa) efflux pumps are involved in resistance of Gram-negative bacteria to most of the natural products.

Anticancer Activities of Six Selected Natural Compounds of Some Cameroonian Medicinal Plants

Background Natural products are well recognized as sources of drugs in several human ailments. In the present work, we carried out a preliminary screening of six natural compounds, xanthone V1 (1); 2-acetylfuro-1,4-naphthoquinone (2); physcion (3); bisvismiaquinone (4); vismiaquinone (5); 1,8-dihydroxy-3-geranyloxy-6-methylanthraquinone (6) against MiaPaCa-2 pancreatic and CCRF-CEM leukemia cells and their multidrug-resistant subline, CEM/ADR5000. Compounds 1 and 2 were then tested in several other cancer cells and their possible mode of action were investigated. Methodology/Findings The tested compounds were previously isolated from the Cameroonian medicinal plants Vismia laurentii (1, 3, 4, 5 and 6) and Newbouldia laevis (2). The preliminary cytotoxicity results allowed the selection of xanthone V1 and 2-acetylfuro-1,4-naphthoquinone, which were then tested on a panel of cancer cell lines. The study was also extended to the analysis of cell cycle distribution, apoptosis induction, caspase 3/7 activation and the anti-angiogenic properties of xanthone V1 and 2-acetylfuro-1,4-naphthoquinone. IC50 values around or below 4 µg/ml were obtained on 64.29% and 78.57% of the tested cancer cell lines for xanthone V1 and 2-acetylfuro-1,4-naphthoquinone, respectively. The most sensitive cell lines (IC50<1 µg/ml) were breast MCF-7 (to xanthone V1), cervix HeLa and Caski (to xanthone V1 and 2-acetylfuro-1,4-naphthoquinone), leukemia PF-382 and melanoma colo-38 (to 2-acetylfuro-1,4-naphthoquinone). The two compounds showed respectively, 65.8% and 59.6% inhibition of the growth of blood capillaries on the chorioallantoic membrane of quail eggs in the anti-angiogenic assay. Upon treatment with two fold IC50 and after 72 h, the two compounds induced cell cycle arrest in S-phase, and also significant apoptosis in CCRF-CEM leukemia cells. Caspase 3/7 was activated by xanthone V1. Conclusions/Significance The overall results of the present study provided evidence for the cytotoxicity of compounds xanthone V1 and 2-acetylfuro-1,4-naphthoquinone, and bring supportive data for future investigations that will lead to their use in cancer therapy.

Semisynthesis and antitumoral activity of 2-acetylfuranonaphthoquinone and other naphthoquinone derivatives from lapachol.

Ozonolysis of lapachol (1), resulting in an unusual formation of a potent antitumor agent 2-acetylfuranonaphthoquinone (3) along with the expected aldehyde 6, is described. The reaction of lapachol (1) with CAN in dry acetonitrile leading to biologically active furanonaphthoquinones is also reported. The antitumoral activity of the tested compounds on human DU-145 prostate carcinoma cells was evaluated following XTT assay. The results revealed that 2-(1-methylethenyl)-2,3-dihydronaphtho[2,3-b]furan-4,9-dione (5), beta-lapachone (10) and dehydro-beta-lapachone diacetate (11) showed 100% inhibition at 25 microg/ml. All the tested samples showed dose-dependent activity.

Quinones and Benzophenones from the Medicinal Plants of Africa

In this chapter, we discuss the chemistry of quinones and benzophenones: classification, nomenclature, biosynthesis, biological activity, and their distribution in nature. Genera such as Newbouldia, Kigelia, Aloe, Euclea, Diospyros, Bulbine, Rumex, and Kniphofia are rich sources of quinines, while the Guttiferae are rich in polyprenylated benzophenones. Most of these African species offer novel derivatives with interesting biological activities, suggesting that these species are potential sources of new drug candidates if properly investigated.

Cobalt mediated ring contraction reaction of lapachol and initial antibacterial evaluation of naphthoquinones derived from lapachol

The synthesis of 2-hydroxy-2-(3-methylbut-2-enyl)-2H-indene-1,3-dione 3, from lapachol which involves a ring contraction via the Hooker intermediate 1,2-dihydroxy-2-(3-methylbut-2-en-1-yl)-3-oxo-2,3-dihydro-1H-indene-1-carboxylic acid 2 is described. Different pyranonaphthoquinone derivatives, obtained in our previous synthetic work, were screened for antimycobacterial (Mycobacterium tuberculosis) activity and against resistant strains of Gram-positive (Bacillus cereus and Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria. The results indicated significant activity of all the tested samples against M. tuberculosis and only moderate activity against the Gram-positive and Gram-negative bacteria.

A new ursane triterpenoic acid and other potential anti-inflammatory and anti-arthritic constituents from EtOAc extracts of Vitellaria paradoxa stem bark.

OBJECTIVE Vitellaria paradoxa (shea tree) is used in traditional medicine for the treatment of various ailments, including, inflammation and fever. Therefore the present research investigates the anti-inflammatory and anti-rheumatic effects of V. paradoxa stem bark extracts in rats and the isolation and characterization of its active constituents. METHODS The anti-inflammatory activity of ethyl acetate extract of V. Paradoxa (VPEE) was evaluated by use of the carrageenan-induced paw oedema model in rats. Moreover, rheumatoid arthritis (RA) was induced by injection of Freunds Completed Adjuvant (FCA) into the subplantar surface of the hind paw of the male Wistar rats. Paw volume was measured plethysmometrically. Joint swelling was measured using electronic vernier caliper. Hot plate test was used to assess the effect of VPEE on hyperalgesia while open field was used to assess the locomotors activity. The relative weight of spleen, liver and thymus was obtained as well as some haematological parameters. Tibiotarsal joint was extracted for histopathology under light microscope. Chemical analysis was carried out by high resolution mass spectrometry and one and two-dimensional NMR techniques. RESULTS LC-MS analysis of the EtOAc extract revealed the presence of a new triterpenoid and several known compounds. The structure of the novel compound was elucidated by means of LC-MS and selected 1D and 2D-NMR experiments. The biological effects of ethyl acetate (VPEE), methanol (VPME) and water extracts (VPAE) of V. paradoxa were tested on carrageenan model of acute inflammation and FCA-induced rheumatoid arthritis animal model. In the carrageenan-induced inflammation, VPEE (150 mg/kg) significant (66.67%) inhibited the first (after 1h) and the second phase (4-6h) of edema formation. On the Complete Freunds adjuvant-induced rheumatoid arthritis, VPEE at the same dose showed a significantly protective effect. On days 19-28th of treatment, the maximum inflammatory percentage was between 9.60 and 8.91% for the VPEE compared to 30.91-24.29% for the controls. All the extracts significantly reduced the score of arthritis but the maximal reduction was obtained with the VPEE on day 24th of the experimentation. The altered haematological parameters in the arthritic rats were significantly recovered to near normal by the treatment with VPEE at the dose of 150 mg/kg. Further histological studies revealed the anti-arthritic activity by preventing cartilage destruction of the arthritic joints of adjuvant arthritic rats. The spleen hypertrophy induced by the FCA was also significantly inhibited. CONCLUSION These findings provide pharmacological basis for the application of the VPEE in inflammatory disorders.

Conversion of lapachol to lomatiol: synthesis of novel naphthoquinone derivatives

Lapachol (1), a naphthoquinone isolated mostly from the plants of the bignoniaceae family has a broad spectrum of biological activities and as a consequence it has been the object of different chemical transformations. Lomatiol (3), another naturally occurring naphthoquinone having structural similarities to lapachol, has been obtained from chemical and microbial transformations of lapachol in very low yields. In the present study, an easy approach for the synthesis of lomatiol (3) from lapachol (1) has been developed using SeO2 oxidation in 90% yield. Lomatiol, under epoxidation conditions afforded novel furano- and pyrano-naphthoquinone derivatives, which are analogues of anticancer agents, 2-acetylfuronaphthoquinone and β-lapachone. Most of the structures were unambiguously confirmed by single crystal X-ray analysis.