| PROF. YENESEW ABIY

Natural products and Drug development

Bio

PROF. YENESEW ABIY

Name: Abiy Yenesew

Nationality: Ethiopian

Date of Birth: November 17th, 1963

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Publications

A new triterpenoid, 3-oxo-12β-hydroxy-oleanan-28,13β-olide (1), and six known
triterpenoids 2–7 were isolated from the root bark of Ekebergia capensis, an African
medicinal plant. A limonoid 8 and two glycoflavonoids 9–10 were found in its leaves. The
metabolites were identified by NMR and MS analyses, and their cytotoxicity was evaluated
against the mammalian African monkey kidney (vero), mouse breast cancer (4T1), human
larynx carcinoma (HEp2) and human breast cancer (MDA-MB-231) cell lines. Out of the
isolates, oleanonic acid (2) showed the highest cytotoxicity, i.e., IC50’s of 1.4 and 13.3 μM
against the HEp2 and 4T1 cells, respectively. Motivated by the higher cytotoxicity of the
crude bark extract as compared to the isolates, the interactions of oleanonic acid (2) with five triterpenoids 3–7 were evaluated on vero cells. In an antiplasmodial assay, seven
of the metabolites were observed to possess moderate activity against the D6 and W2
strains of P. falciparum (IC50 27.1–97.1 μM), however with a low selectivity index
(IC50(vero)/IC50(P. falciparum-D6) < 10). The observed moderate antiplasmodial activity
may be due to general cytotoxicity of the isolated triterpenoids.

Keywords: Ekebergia capensis; tritepenoid; antiplasmodial; cytotoxicity; Vero; 4T1;
HEp2; MDA-MB-231; 3-oxo-12β-hydroxy-oleanan-28,13β-olide

Yenesew, A, Muiva-Mutisya L, Macharia B, Heydenreich M, Andreas Koch, Hoseah M. Akala SDLOK. 2014. 6α-Hydroxy-α-toxicarol and (+)-Tephrodin with antiplasmodial activities from Tephrosia species. Phytochemistry Letters . Abstractpaper_75_muiva_et_al_phyto_2014.pdf

The CH2Cl2/MeOH (1:1) extract of the roots of Tephrosia villosa showed good antiplasmodial activity against the chloroquine-sensitive (D6) and chloroquine-resistant (W2) strains of Plasmodium falciparum with IC50 values of 3.1 ± 0.4 and 1.3 ± 0.3 μg/mL, respectively. Chromatographic separation of the extract yielded a new rotenoid, 6α-hydroxy-α-toxicarol, along with five known rotenoids, (rotenone, deguelin, sumatrol, 12a-hydroxy-α-toxicarol and villosinol). Similar treatment of the extract of the stem of Tephrosia purpurea (IC50 = 4.1 ± 0.4 and 1.9 ± 0.2 μg/mL against D6 and W2 strains of P. falciparum, respectively) yielded a new flavone having a unique substituent at C-7/C-8 [trivial name (+)-tephrodin], along with the known flavonoids tachrosin, obovatin methyl ether and derrone. The relative configuration and the most stable conformation in (+)-tephrodin was determined by NMR and theoretical energy calculations. The rotenoids and flavones tested showed good to moderate antiplasmodial activities (IC50 = 9 − 23 μМ). Whereas the cytotoxicity of rotenoids is known, the flavones (+)-tephrodin and tachrosin did not show significant cytotoxicity (IC50 > 100 μМ) against mammalian African monkey kidney (vero) and human larynx carcinoma (HEp2) cell lines.

Yenesew, A, Gumula I, Erdélyi M, Patrick. A, J Isaiah Omolo Ndiege PS, Omolo, N, Sunnerhagen P. 2014. Cytotoxic and Antioxidant Flemingins G-P from the Leaves of Flemingia grahamiana. Journal of Natural Products . Abstractpaper_76_ivan_et_al_jnp_2014_77_2060_2067.pdf

The known flemingins A-C (1-3) and nine new chalcones, named flemingins G-O (4-12), along with deoxyhomoflemingin (13) and emodin (14) were isolated from a leaf extract of Flemingia grahamiana. The isolated chalcones were found to have a geranyl substituent modified into a chromene ring possessing a residual chain, as shown by spectroscopic methods. The leaf extract showed an IC50 value of 5.9 μg/mL in a DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging assay. The chalcones flemingins A, B, C, G, and H were active in the DPPH radical scavenging assay (ED50 4.4-8.9 μM), while flemingins A and C showed cytotoxicity against MCF-7 human breast cancer cells (IC50 8.9 and 7.6 μM, respectively).

Yenesew, A, Atilaw Y, Heydenreich, Ndakala A, Hoseah M, Akala, M Kamau E. 2014. 3-Oxo-14α,15α-epoxyschizozygine: A new schizozygane indoline alkaloid from Schizozygia coffaeoides. Phytochemistry Letters . 10:28-31. Abstractpaper_73_atilaw_et_al_phyto_2014.pdf

The stem bark extract of Schizozygia coffaeoides (Apocynaceae) showed moderate antiplasmodial activity (IC50 = 8–12 μg/mL) against the chloroquine-sensitive (D6) and chloroquine-resistant (W2) strains of Plasmodium falciparum. Chromatographic separation of the extract led to the isolation of a new schizozygane indoline alkaloid, named 3-oxo-14α,15α-epoxyschizozygine. In addition, two dimeric anthraquinones, cassiamin A and cassiamin B, were identified for the first time in the family Apocynaceae. The structures of the isolated compounds were deduced on the basis of spectroscopic evidence. The schizozygane indole alkaloids showed good to moderate antiplasmodial activities (IC50 = 13–52 μМ).

Yenesew, A, Judith O, Saffudin D, Catherine L. 2014. Phytochemical screening of Dierama cupuliflorum Klatt. (Iridaceae). Journal of Pharmacy Research. 8:589-592. Abstractpaper_72_judith_et_al_jou_of_pharma._res._2014.pdf

Background: Plants continue to play a vital role in their therapeutic value. This is because of the vast secondary metabolites that many of them produce. These natural products have been utilised as single or in combination with other compounds for utilization as source of drugs for many ailments in form of antibacterials, antifungals, antivirals, antihelminthes, and antimalarials among others. Plants evaluated phytochemically in most cases have previous reports on biological activity, ethnomedicinal or traditional medicine usage. However, many other plants with no such previous reports may be as important with variety of natural products with potential significance in pharmaceuticals for drug development. Dierama cupuliflorum is one such plant. The aim of the present study was to investigate the presence of phytochemicals in this plant. Method : The organic solvent extracts from Methanol: Dichloromethane (1:1) along with dry powder/ground portions from corms and aerial parts were screened for the presence of selected phytochemicals using standard chemical procedures. Results: Phytochemical screening revealed the presence of terpenoids, alkaloids, saponins, tannins, flavanoids, glycosides and anthraquinones. More phytochemicals were detected in corms than in the aerial parts. Conclusion: Although there is no available report on the use of this plant for medicinal purposes, the phytochemical data presented here has demonstrated that this plant has the potential to be used significantly for therapeutic purposes in many health challenges. This study has therefore laid down a good foundation for future studies on this plant whose bioactivity studies are currently underway.

Yenesew, A, L. K., Omosa, Beatrice, Amugune, Ndunda B, Milugo TKTK, Heydenreich M, Midiwo JO. 2014. Antimicrobial flavonoids and diterpenoids from Dodonaea angustifolia. South African Journal of Botany. . 91, :58-62.. Abstractpaper_67_omosa_et_al_south_africa_jou..2014.pdf

The surface exudates of the leaves of Dodonaea angustifolia from Ngong forest population (6 km from Nairobi city center, Kenya) demonstrated antimicrobial activity against Gram-negative (Escherichia coli), Gram-positive (Staphylococcus aureus and Bacillus pumilus) bacteria and the fungus Sacchromyces cerevisiae. Chromatographic separation of the exudates yielded eight methylated flavonoids; 5-hydroxy-3, 4′,7-trimethoxyflavone (1), 3,5-dihydroxy-4′,7-dimethoxyflavone (2), santin (3), kumatakenin (4), rhamnocitrin (5), isokaempferide (6), 3,4′,5,7, tetrahydroxy-6-methoxyflavone (7), pinocembrin (8); two clerodanes, dodonic acid (9) and 2β-hydroxyhardwickiic acid (10) and one labdane; (ent-3β,8α)-15,16-epoxy-13(16),14-labdadiene-3,8-diol (11) diterpenoids. The flavonoid aglycones; 6, 7 and the clerodane diterpenoids; 9 and 10 and labdane diterpenoid, 11 were isolated for the first time from this plant species. The structures of the isolated compounds were identified using ultraviolet (UV), mass spectroscopy (MS), one dimension (1D) and two dimension (2D) nuclear magnetic resonance (NMR) spectroscopy and by comparison of the spectral data with literature. The quercetin derivative, 3,4′,5-trihydroxy-3′,7-dimethoxyflavone (12) showed broad spectrum antibacterial activities against E. coli and B. pumilus with minimum inhibition concentration (MIC) values less than 31.25 μg/well and against S. aureus with MIC below 62.5 μg/well. This compound showed poor antifungal activity against S. cerevisiae (MIC < 500 μg/well). Good antifungal activities were observed for 5,4′-dihydroxy-7-methoxyflavanone (13) and hautriwaic acid lactone (14) against S. cerevisiae with MIC values less than 7.8 μg/well. The most active antifungal compound was 5,7-dihydro-3,4′,6-trimethoxyflavone (3, santin) with an MIC value less than 3.9 μg/well against S. cerevisiae. The rest of the compounds exhibited weak to moderate activities. For comprehensive structure activity relationship studies (SAR), hautriwaic acid lactone (14), hautriwaic acid (15), penduletin (16) isolated from the surface exudates of D. angustifolia from Voi (200 km from Mombasa city center, Kenya) and 12 and 13 from Senecio roseiflorus isolated earlier were included in the bioassays.

Yenesew, A, Derese, S., Barasa, L., Akala HM, Yusuf, A.O., Kamau E, Heydenreich. 2014. 4'-Prenyloxyderrone from the stem bark of Millettia oblata ssp. teitensis and the antiplasmodial activities of isoflavones from some Millettia species.. Phytochemistry Letters ,. 8:69-72. Abstractpaper_68_derese_et_al_phyto_2014.pdf

The CH2Cl2/MeOH (1:1) extract of the stem bark of Millettia oblata ssp. teitensis showed antiplasmodial activity (IC50 = 10–12 μg/mL) against the chloroquine-sensitive (D6) and chloroquine-resistant (W2) strains of Plasmodium falciparum. Chromatographic separation of the extract led to the isolation of a new isoflavone, 4′-prenyloxyderrone (1), together with known isoflavones (8-O-methylretusin, durmillone, maximaisoflavone B, maximaisoflavone H and maximaisoflavone J), a rotenoid (tephrosin) and a triterpene (lupeol). Similar investigation of Millettia leucantha resulted in the identification of the isoflavones afrormosin and wistin, and the flavone chrysin. The identification of these compounds was based on their spectroscopic data. Five of the isoflavones isolated from these plants as well as 11 previously reported compounds from Millettia dura were tested and showed good to moderate antiplasmodial activities (IC50 = 13–53 μM), with the new compound, 4′-prenyloxyderrone, being the most active (IC50 = 13–15 μM).

Yenesew, A, Sunnerhagen, P., Erdelyi M, Abdissa N, Induli, M., Fitzpatrick P, Alao JP, Landberg G. 2014. Cytotoxic Quinones from the Roots of Aloe dawei.. Molecules. 19,:3264-3273. Abstractpaper_69_abdissa_et_al_molecules_2014.pdf

Seven naphthoquinones and nine anthraquinones were isolated from the roots of Aloe dawei by chromatographic separation. The purified metabolites were identified by NMR and MS analyses. Out of the sixteen quinones, 6-hydroxy-3,5-dimethoxy-2-methyl-1,4-naphthoquinone is a new compound. Two of the isolates, 5,8-dihydroxy-3-methoxy-2-methylnaphthalene-1,4-dione and 1-hydroxy-8-methoxy-3-methylanthraquinone showed high cytotoxic activity (IC₅₀ 1.15 and 4.85 µM) on MCF-7 breast cancer cells, whereas the others showed moderate to low cytotoxic activity against MDA-MB-231 (ER Negative) and MCF-7 (ER Positive) cancer cells.

Yenesew, A, N A, Heydenreich M, Midiwo JO, Ndakala A, Majer Z, Neumann B, Stammler H-G, Sewald N. 2014. 8-Hydroxy-6-methylxanthone-1-carboxylic acid and 6',8-O-dimethylknipholone from the roots of Bulbine frutescens.. Phytochemistry Letters . 9:67-73. Abstractpaper_70_abdissa_et_al_phyto_2014.pdf

Phytochemical investigation of the dichloromethane/methanol (1:1) extract of the roots of Bulbine frutescens led to the isolation of a new xanthone, 8-hydroxy-6-methylxanthone-1-carboxylic acid (1) and a new phenylanthraquinone, 6′,8-O-dimethylknipholone (2) along with six known compounds. The structures were elucidated on the basis of NMR and MS spectral data analyses. The structure of compound 1 was confirmed through X-ray crystallography which was then used as a reference to propose the revision of the structures of six seco-anthraquinones into xanthones. The isolated compounds were evaluated for cytotoxicity against human cervix carcinoma KB-3-1 cells with the phenylanthraquinone knipholone being the most active (IC50 = 0.43 μM). Two semi-synthetic knipholone derivatives, knipholone Mannich base and knipholone-1,3-oxazine, were prepared and tested for cytotoxic activity; both showed moderate activities (IC50 value of 1.89 and 2.50 μM, respectively).

Yenesew, A, Bosire CM, Deyou T, Kabaru JM, Kimata DM. 2014. Larvicidal activities of extracts and rotenoids from Millettia usaramensis subspecies usaramensis on Aedes aegypti (Linnaeus, 1762) (Diptera: Culicidae).. Journal of Asia-Pacific Entomology . 17(3):531-535. Abstractpaper_71_bosire_et_al__asia-2014.pdf

The dichloromethane/methanol (1:1) extract of the stem bark of Millettia usaramensis subspecies usaramensis was tested for its larvicidal activity against the 4th instar Aedes aegypti larvae and demonstrated activity with LC50 value of 50.8 ± 0.06 μg/mL at 48 h. Compounds isolated from the extract were also tested for their larvicidal activities, and the rotenoid usararotenoid-A (LC50 4.3 ± 0.8 μg/mL at 48 h) was identified as the most active principle. This compound appears to be the first rotenoid having a trans-B/C ring junction and methylenedioxy group at C-2/C-3 with high larvicidal activity. Related rotenoids with the same configuration at the B/C-ring junction did not show significant activity at 100 μg/mL.

2013

Yenesew, A, Abdissa, N., Ndakala A, Induli, M., Akala, H.M., Heydenrich, M., Midiwo, J.O.. 2013. Knipholone Cyclooxanthrone and an Anthraquinone Dimer with Antiplasmodial Activities from the Roots of Kniphofia foliosa.. Phytochemistry Letters . 6:241-245. Abstractpaper_62_abdissa_phytol-2013.pdf

A new phenylanthrone, named knipholone cyclooxanthrone and a dimeric anthraquinone, 10-methoxy-
10,70-(chrysophanol anthrone)-chrysophanol were isolated from the roots of Kniphofia foliosa together
with the rare naphthalene glycoside, dianellin. The structures were determined by NMR and mass
spectroscopic techniques. The compounds showed antiplasmodial activities against the chloroquineresistant (W2) and chloroquine-sensitive (D6) strains of Plasmodium falciparum with 10-methoxy-10,70-(chrysophanol anthrone)-chrysophanol being the most active with IC50 values of 1.17 0.12 and 4.07 1.54 mg/ml, respectively.

Yenesew, A, Endale M, M., Erdelyi, Ekberg A, HM A, Ndakala A, A., Sunnerhagen. 2013. Anthraquinonesof the roots of Pentas micrantha.. Molecules . 18,:311-321.. Abstractpaper_61_endale_et_al_molecules-2013-18-00311.pdf

Pentas micrantha is used in the East African indigenous medicine to treat malaria. In the first investigation of this plant, the crude methanol root extract showed moderate antiplasmodial activity against the W2- (3.37 μg/mL) and D6-strains (4.00 μg/mL) of Plasmodium falciparum and low cytotoxicity (>450 μg/mL, MCF-7 cell line). Chromatographic separation of the extract yielded nine anthraquinones, of which 5,6-dihydroxylucidin-11-Omethyl ether is new. Isolation of a munjistin derivative from the genus Pentas is reported
here for the first time. The isolated constituents were identified by NMR and mass spectrometric techniques and showed low antiplasmodial activities.

Keywords: anthraquinone; malaria; Pentas micrantha; Rubiaceae; 5,6-dihydroxylucidin-11-O-methyl ether 1.

Yenesew A., Peggoty Mutai, Matthias Heydenreich GTGMKC. 2013. 3-Hydroxyisoflavanones from the stem bark of Dalbergia melanoxylon: Isolation, antimycobacterial evaluation and molecular docking studies. Phytochemistry Letters . 6 :671-675.. Abstractpaper_65_mutai_et_al_phyto_2013.pdf

Two new 3-hydroxyisoflavanones, (S)-3,4′,5-trihydroxy-2′,7-dimethoxy-3′-prenylisoflavanone (trivial name kenusanone F 7-methyl ether) and (S)-3,5-dihydroxy-2′,7-dimethoxy-2″,2″-dimethylpyrano[5″,6″:3′,4′]isoflavanone (trivial name sophoronol-7-methyl ether) along with two known compounds (dalbergin and formononetin) were isolated from the stem bark of Dalbergia melanoxylon. The structures were elucidated using spectroscopic techniques. Kenusanone F 7-methyl ether showed activity against Mycobacterium tuberculosis, whereas both of the new compounds were inactive against the malaria parasite Plasmodium falciparum at 10 μg/ml. Docking studies showed that the new compounds kenusanone F 7-methyl ether and sophoronol-7-methyl ether have high affinity for the M. tuberculosis drug target INHA.

Yenesew A., Martha Induli, Meron Gebru NAHAIWRBMHSM. 2013. Antiplasmodial Quinones from the Rhizomes of Kniphofia foliosa. Natural Products Comunications . 8:1261-1264. Abstractpaper_64_induli_et_al-npc-2013.pdf

Extracts of the rhizomes of Kniphofia foliosa exhibited antiplasmodial activities against the chloroquine-sensitive (D6) and chloroquine-resistant (W2) strains of Plasmodium falciparum with IC50 values of 3-5 microg/mL. A phenyloxanthrone, named 10-acetonylknipholone cyclooxanthrone (1) and an anthraquinone-anthrone dimer, chryslandicin 10-methyl ether (2), were isolated from the rhizomes, along with known quinones, including the rare phenylanthraquinone dimers, joziknipholones A and B. The structures of these compounds were determined based on spectroscopic data. This is the second report on the occurrence of the dimeric phenylanthraquinones in nature. In an in vitro antiplasmodial assay of the isolated compounds, activity was observed for phenylanthraquinones, anthraquinone-anthrone dimers and dimeric phenylanthraquinones, with joziknipholone A being the most active. The new compound, 10-acetonylknipholone cyclooxanthrone, also showed anti-plasmodial activity. In an in vivo assay, knipholone anthrone displayed marginal antimalarial activity.

Yensew, A. 2013. Limitations to Use of Infrared Spectroscopy for Rapid Determination of Carbon-Nitrogen and Wood Density for Tropical Species. Advances in Analytical Chemistry. Advances in Analytical Chemistry . 3(3) Abstractpaper_63_kennedy10.5923.j.aac_.20130303.01.pdf

Infrared (IR) spectroscopy was used as a rapid and non-destructive method to determine, carbon (C), nitrogen (N) and tree wood density.A total of 82 sample cores were scanned in the reflectance mode from 4000 to 400 cm-1 for mid-infrared (MIR) spectra and from 8000 to 4000cm-1 and 11000-4000cm-1 for near infrared (NIR) spectra. The reference values for C and N were measured using combustion method while wood density was calculated using auger method. Calibration equations were developed using partial least-squares and first derivative spectra. Root mean square error (RMSEP) was used to calculate prediction error. Prediction of Cusing MIR spectra gave R2 = 0.59, RMSEP = 0.02; NIR spectra R2 = 0.50, RMSEP = 0.02, whileN prediction usingMIR spectra had R2 = 0.54, RMSEP = 0.22; NIR spectra R2 = 0.48, RMSEP =0.24. Wood density prediction was fair for MIR (R2= 0.79, RMSEP = 0.14); NIR (R2= 0.69, RMSEP = 0.17).Improved predictions using NIR were for extendedspectral range;though accuracies were inferior to MIR. Both MIR and NIR models showed good potentials to be used as rapid and cost effective method of predicting C-N andwood density.

Keywords Infrared Spectroscopy, Partial Least Squares Regression,Carbon, Nitrogen,Wood Density

2012

Yenesew A., Endale, M. AAREDNMWSJPHM. 2012. Antiplasmodial Quinones from Pentas longiflora and Pentas lanceolata. Planta medica . 78:31-35. Abstractpaper_53_endale_et_al_planta_medica_2012-78-31-35.pdf

The dichloromethane/methanol (1 : 1) extracts of the roots of PENTAS LONGIFLORA and PENTAS LANCEOLATA showed low micromolar (IC (50) = 0.9-3 µg/mL) IN VITRO antiplasmodial activity against chloroquine-resistant (W2) and chloroquine-sensitive (D6) strains of PLASMODIUM FALCIPARUM. Chromatographic separation of the extract of PENTAS LONGIFLORA led to the isolation of the pyranonaphthoquinones pentalongin ( 1) and psychorubrin ( 2) with IC (50) values below 1 µg/mL and the naphthalene derivative mollugin ( 3), which showed marginal activity. Similar treatment of PENTAS LANCEOLATA led to the isolation of eight anthraquinones ( 4-11, IC (50) = 5-31 µg/mL) of which one is new (5,6-dihydroxydamnacanthol, 11), while three - nordamnacanthal ( 7), lucidin- ω-methyl ether ( 9), and damnacanthol ( 10) - are reported here for the first time from the genus PENTAS. The compounds were identified by NMR and mass spectroscopic techniques.

Yenesew, A. 2012. Four Isoflavanones from the stem bark of Platycelphium voënse.. Phytochemistry Letters . 5:150-154. Abstractpaper_54_ivan_et_al_phytol-2012.pdf

From the stem bark of Platycelphium voe¨nse (Leguminosae) four new isoflavanones were isolated and
characterized as (S)-5,7-dihydroxy-20,40-dimethoxy-30-(300-methylbut-200-enyl)-isoflavanone (trivial
name platyisoflavanone A), ()-5,7,20-trihydroxy-40-methoxy-30-(300-methylbut-200-enyl)-isoflavanone
(platyisoflavanone B), 5,7-dihydroxy-40-methoxy-200-(2000-hydroxyisopropyl)-dihydrofurano-[400,500:30,20]-
isoflavanone (platyisoflavanone C) and 5,7,20,300-tetrahydroxy-200,200-dimethyldihydropyrano-[500,600:30,40]-isoflavanone (platyisoflavanone D). In addition, the known isoflavanones, sophoraisoflavanone A and glyasperin F; the isoflavone, formononetin; two flavones, kumatakenin and isokaempferide; as well as two triterpenes, betulin and b-amyrin were identified. The structures were elucidated on the basis of spectroscopic evidence. Platyisoflavanone A showed antibacterial activity against Mycobacterium tuberculosis in the microplate alamar blue assay (MABA) with MIC = 23.7 mM, but also showed cytotoxicity (IC50 = 21.1 mM) in the vero cell test.

Yenesew, A. 2012. The Antiplasmodial and Radical Scavenging Activities of Flavonoids of Erythrina burttii.. Acta Tropica . 123:123-127. Abstract

The acetone extract of the root bark of Erythrina burttii showed in vitro antiplasmodial activity against
the chloroquine-sensitive (D6) and chloroquine-resistant (W2) strains of Plasmodium falciparum with
IC50 values of 0.97 ± 0.2 and 1.73 ± 0.5 g/ml respectively. The extract also had radical scavenging activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical with an EC50 value of 12.0 g/ml. The isoflav-3-enes burttinol-A and burttinol-C, and the 2-arylbenzofuran derivative burttinol-D were identified as the most active antiplasmodial (IC50 < 10 M) and free radical scavenging (EC50 ca. 10 M) principles. The acetone extract of E. burttii at 800 mg/kg/day, in a 4-day Plasmodium berghei ANKA suppressive test, showed in vivo antimalarial activity with 52% hemosuppression. In the same in vivo test, marginal activities were also
observed for the extracts of the root and stem bark of Erythrina abyssinica and the root bark of Erythrina
sacleuxii.

Yenesew, A. 2012. Naphthoquinones from the roots of Aloe secundiflora (Asphodelaceae). Phytochemistry Letters . 5:506-509. Abstractpaper_56_induli_et_al_phytol_-2012.pdf

Two new naphthoquinones, 5-hydroxy-3,6-dimethoxy-2-methylnaphthalene-1,4-dione and 5,8-dihydroxy-
3-methoxy-2-methylnaphthalene-1,4-dione, were isolated from the roots of Aloe secundiflora together with the known compounds chrysophanol, helminthosporin, isoxanthorin, ancistroquinone C, aloesaponarins I and II, aloesaponols I and II, laccaic acid D methyl ester and asphodelin. The structures were elucidated based on spectroscopic evidence. This appears to be the first report on the occurrence of naphthoquinones in the genus Aloe. Aloesaponarin I and 5-hydroxy-3,6-dimethoxy-2-methylnaphthalene-1,4-dione showed anti-bacterial activity against Mycobacterium tuberculosis with MIC values of 21–23 mg/mL in the Microplate Alamar Blue Assay (MABA) and Low Oxygen Recovery Assay (LORA); 5-hydroxy-3,6-dimethoxy-2-methylnaphthalene-1,4-dione also showed cytotoxicity against the Vero cell line (IC50 = 10.2 mg/mL)

Yenesew, A. 2012. Busseihydroquinones A-D from the Roots of Pentas bussei. Journal of Natural Products. 75 :1299-1304.. Abstractpaper_57_endale_et_al_j_nat_prod_2012.pdf

Four new naphthohydroquinones, named busseihydroquinones A−D (1−4), along with a known homoprenylated dihydronaphthoquinone (5), were isolated from the CH2Cl2/MeOH (1:1) extract of the roots of Pentas bussei. Although the genus Pentas is frequently used by traditional healers for the treatment of malaria, only marginal activities against the chloroquine-sensitive (D6) and the chloroquineresistant (W2) strains of Plasmodium falciparum were observed for the crude root extract and the isolated constituents of this plant.

Yenesew, A. 2012. Antimicrobial and Anticancer Carvotacetone Derivativesof Sphaeranthus. Natural Product Communications . 7:1123-1126. Abstractpaper_58_machumi_npc_publication-sphaeranthus_bullatus-2012.pdf

The CH2Cl2-MeOH (1:1) extract of the aerial parts of Sphaeranthus bullatus, an annual herb native to tropical East Africa, showed activity against chloroquine sensitive D6 (IC50 9.7 μg/mL) and chloroquine resistant W2 (IC50 15.0 μg/mL) strains of Plasmodium falciparum. Seventeen secondary metabolites were isolated from the extract through conventional chromatographic techniques and identified using various spectroscopic methods. The compounds were evaluated for their in vitro antiplasmodial, antileishmanial and anticancer activities revealing activity of four carvotacetone derivatives, namely 3-acetoxy-7-hydroxy-5-tigloyloxycarvotacetone (1), 3,7-dihydroxy-5-tigloyloxycarvotacetone (2), 3-acetoxy-5,7-dihydroxycarvotacetone (3) and 3,5,7-trihydroxycarvotacetone
(4); with antiplasmodial IC50 values of 1.40, 0.79, 0.60 and 3.40 μg/mL, respectively, against chloroquine sensitive D6 strains of P. falciparum;
antiplasmodial activity of IC50 2.00, 0.90, 0.68 and 2.80 μg/mL, respectively, against chloroquine resistant W2 strains of P. falciparum; antileishmanial IC50
values of 0.70, 3.00, 0.70 and 17.00 μg/mL, respectively, against the parasite L. donovanii promastigotes, and anticancer activity against human SK-MEL, KB,
BT-549 and SK-OV-3 tumor cells, with IC50 values between <1.1 - 5.3 μg/mL for 1-3. In addition, cytotoxic effects of the active compounds were evaluated against monkey kidney fibroblasts (VERO) and pig kidney epithelial cells (LLC-PK11). The structures of carvotacetone derivatives were determined by 1D and 2D NMR spectroscopy; the absolute stereochemical configuration of 3-acetoxy-7-hydroxy-5-tigloyloxycarvotacetone (1) was determined as 3R, 4R, 5S by circular dichroism, specific rotation, 1H NMR and 2D NMR ROESY and NOESY experiments.

Keywords: Sphaeranthus bullatus, Asteraceae, Antiplasmodial, Antileishmanial, Anticancer, Carvotacetones.

Yenesew, A. 2012. Antinocieptive Activities of the Root Extracts of Rhus natalensis Kraus and Senna singueana. Phytopharmacology . 2:1-6. Abstractpaper_59_karuki_et_al-2012.pdf

Rhus natalensis and Senna singuaenae are traditional African plants commonly used as medicinal plant in East Africa for the management of pain. The plants are used for management of rheumatism among others. This study investigated the antinociceptive activities of R. natalensis and S. singuaenae in Swiss albino mice using the tail-flick and hot plate tests. Extract solvent (vehicle), morphine and aspirin were employed as controls. Root extract of R. natalensis (100 and 200 mg /kg) and 100 mg /kg of S. singuaenae showed no significant antinociceptive activity in the hot plate while the 200mg /kg of S. singuaenae showed significant antinociceptive activity (p<0.05). In the tail flick tests, root extract of R. natalensis (100 and 200 mg / kg) showed highly significant antinociceptive activity (p<0.01) while 200mg / kg of S. singuaenae showed significant antinociceptive activity (p<0.05) compared to the controls. The 100 mg /kg of S. singuaenae showed no significant antinociceptive activity in the tail flick. This study lends support to the anecdotal evidence for use of R. natalensis and S. singuaenae in the management of painful conditions.

Keywords: Rhus natalensis; Senna singuaenae; analgesic; Rhus natalensis; Senna singuaenae; rheumatism

Yenesew, A. 2012. Antinocieptive activity of Toddalia asiatica (L) Lam. in models of central and peripheral pain. Phytopharmacology . 3(1):122-129. Abstractpaper_60_kariuki_et_al_phytopharmacology_2012.pdf

Toddalia asiatica within the context of traditional African medicine is a commonly used medicinal plant in East Africa for the management of pain and inflammatory conditions. It is used by the Masai in both Kenya and Tanzania for management of rheumatism among others. The present study was undertaken to investigate the antinociceptive activities of T. asiatica in Swiss albino mice in acetic acid-induced writhing, tail-flick and hot plate pain tests. The extract solvent (vehicle), morphine and aspirin were employed as negative and positive controls respectively. The acetic acid -induced writhing test was used as the screening test and as the root bark extract was found to be more potent than the leaf extract, the former was investigated using the hot plate and the tail flick tests. The root bark extract (200 mg / kg) showed highly significant (p < 0.001) antinociceptive activity in the hot plate and the tail flick tests. The 100mg/kg dose showed significant (p < 0.05) activity in the tail flick test but not significant in the hot plate test. The present study, therefore lends support to the anecdotal evidence for use of T. asiatica in the management of painful conditions.

2011

Yenesew, A. 2011. Phytochemical and Antimicrobial Investigation of Girardinia diversifolia (Link) Friis (Urticaceae). East and Central African Journal of Pharmaceutical Sciences. 14:89-94.njogu_et_al-2011-ecajps.pdf

Bosire C. M., Kabaru J.M., YKADM. 2011. A Toxicological Study of Millettia usaramensis Stem Bark Extract on Aedes aegypti (Mosquito), Schistocerca gregaria (Desert Locust) and Mus musculus (Mouse). 11h NAPRECA Symposium. :298-300., Nairobi. Kenyabook_of_extended_abstracts_for_the_14th_napreca_symposium_and_aamps_ethnoveterinary_medicine_symposium_2.pdf

Yenesew, A. 2011. Antiplasmodial and Radical Scavenging Activities of Flavonoids from Kenyan Erythrina species. The 14th NAPRECA Symposium and AAMPS Ethnoveterinary Medicine Symposium. :104-106.: NAPRECAabstract-yenesew_et_al-napreca-2011.pdf

Yenesew A., Juma, W.P. AEMHOGPWIHMFL. 2011. Terpurinflavone: An Antiplasmodial Flavone from The Stem of Tephrosia purpurea. Phytochemistry Letters .. 4:176-178. Abstractpaper_51_juma_et_al_phytol-2011.pdf

The stem extract of Tephrosia purpurea showed antiplasmodial activity against the D6 (chloroquine-sensitive) and W2 (chloroquine-resistant) strains of Plasmodium falciparum with IC50 values of 10.47 ± 2.22 μg/ml and 12.06 ± 2.54 μg/ml, respectively. A new prenylated flavone, named terpurinflavone, along with the known compounds lanceolatin A, (−)-semiglabrin and lanceolatin B have been isolated from this extract. The new compound, terpurinflavone, showed the highest antiplasmodial activity with IC50 values of 3.12 ± 0.28 μM (D6) and 6.26 ± 2.66 μM (W2). The structures were determined on the basis of spectroscopic evidence.

PROF. YENESEW ABIY

Ph.D. (1997) and MSc. (1992) in Chemistry, University of Nairobi. BSc.(1984) in Chemistry, Addis Ababa University, Ethiopia

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