Sesquiterpene lactones from Vernonia cinerascens sch. bip. and their in vitro antitrypanosomal activity

In the endeavor to obtain new antitrypanosomal agents, particularly sesquiterpene lactones, from Kenyan plants of the family Asteraceae, Vernonia cinerascens Sch. Bip. was investigated. Bioactivity-guided fractionation and isolation in conjunction with LC/MS-based dereplication has led to the identification of vernodalol (1) and isolation of vernodalin (2), 11β,13-dihydrovernodalin (3), 11β,13-dihydrovernolide (4), vernolide (5), 11β,13-dihydrohydroxyvernolide (6), hydroxyvernolide (7), and a new germacrolide type sesquiterpene lactone vernocinerascolide (8) from the dichloromethane extract of V. cinerascens leaves. Compounds 3-8 were characterized by extensive analysis of their 1D and 2D NMR spectroscopic and HR/MS spectrometric data. All the compounds were evaluated for their in vitro biological activity against bloodstream forms of Trypanosoma brucei rhodesiense and for cytotoxicity against the mammalian cell line L6. Vernodalin (2) was the most active compound with an IC50 value of 0.16 µM and a selectivity index of 35. Its closely related congener 11β,13-dihydrovernodalin (3) registered an IC50 value of 1.1 µM and a selectivity index of 4.2

Screening of Indigofera lupatana Baker F. root extracts for antibacterial activities

Herbal remedies as cheap alternatives to conventionalmedicine have contributed significantly to rurallivelihoods. Apart from the traditional healerspracticing herbal medicine, many people are involved incollecting and trading medicinal plants. The WorldHealth Organization (WHO) estimates that 80% of theworld’s population depends on medicinal plants fortheir primary health care (Mothana et al, 2008; Ngoci etal, 2011). The use of traditional medicine has beenexplored globally and is widely used in developingcountries as an alternative or to complementconventional medicine (Rates, 2001; Gupta et al, 2010).Natural products, either as pure compounds or asstandardized plant extracts, provide exceptionalopportunities for new drug leads because of theunmatched chemical diversity of naturally derivedcompounds (Cowan, 1999; Parekh and Chanda, 2007;Mariita et al, 2010; Ngoci et al, 2011). Scientific interestin medicinal plants has burgeoned due to therecognized efficacy of plant derived drugs and everpresentconcerns about the side effects of modernmedicinal substances. This has fuelled the intensiveinvestigation of new molecular structures from theplant kingdom as potential medicinal compounds(Mariita et al, 2010). As a result, drugs derived fromunmodified natural products or semi-synthetic drugsobtained from natural sources accounted for 78% of thenew drugs approved by the United States Food andDrug Administration (FDA) between 1983 and 1994(Suffredini et al, 2006; Ngoci et al, 2011). Thisunderscores the importance of screening naturalproducts.Infectious diseases are a leading cause of human andanimal mortality. This is further aggravated by the rapiddevelopment of multi-drug resistance to available antimicrobialagents (Doughart and Okafor, 2007; Ngoci etal, 2011), their limited anti-microbial spectrum, theirside effects (Huie, 2002), and emergence and reemergenceof opportunistic infections. Therefore,studies aimed at identifying and characterizing of thesubstances that exhibit activity against infectious microorganisms,yet showing no cross resistance withexisting antibiotics, are required (Olila et al, 2001). Inrecent years, pharmaceutical companies have focusedon developing drugs from natural products thatpromises to counter the limitations of conventionalantibiotics (Doughart and Okafor, 2007).The bio-activity of natural products is due tophytochemicals, a group of secondary metabolites oftenelaborated for the plant defense against pests andherbivores or to gain an advantage over competingagents. These phytochemicals inadvertently also protecthumans against pathogens (Ngoci et al, 2011). Somephytochemicals are known to have antimicrobialproperties, immune-modulative properties, providenutrition for normal cell health and repairs, inhibitcarcinogens and act as antioxidants.Indigofera lupatana Baker F., locally called ‘mugiti’ bythe Mbeere community in Kenya, is a woody shrubfound in Acacia-Combretum ecological zones of Mbeere.It is widely used for its perceived medicinal value intreating coughs and diarrhea (Riley and Brokensha,1988; Ngoci et al, 2011), gonorrhea and pleurisy(Kokwaro, 1993; Ngoci et al, 2011).There is apparently no documented scientific report onanti-microbial properties of this plant. This lack ofscientific corroboration has often constituted a majorconstraint to the consideration of the use of herbalremedies in conjunction with or as an affordablealternative to conventional medical treatment (Okeke etal, 2001). Knowledge of the chemical constituents ofplants is desirable not only for the discovery oftherapeutic agents, but also because such informationmay be important in identifying new sources ofsubstances of economic value such as tannins, oils,gums, and precursors for the synthesis of complexchemical substances. In addition, the knowledge of thechemical constituents of plants would further bevaluable in discovering the actual value of folkloricremedies (Mojab et al, 2003).This study was therefore undertaken to determine theantibacterial properties of hexane, ethyl acetate anddichloromethane root extracts of I. lupatana Baker F

ANTIMICROBIAL ACTIVITY OF ESSENTIAL OILS OF OCIMUM GRATISSIMUM L. FROM DIFFERENT POPULATIONS OF KENYA

Hydro-distilled volatile oils from the leaves of Ocimum gratissimum L. (Lamiaceae) of 13 populations of different silvicultural zones were evaluated for antimicrobial activity against Gram positive (Staphylococcus aereus, Bacillus spp.) and Gram negative (Escherichia coli, Pseudomonas aeruginosa, Samonella typhi, Klebisiella pneumoniae, Proteus mirabilis) bacteria and a pathogenic fungus, Candida albicans. All the essential oils are active to the tested microbiles with different strength. The highest antimicrobial activity against Gram positive bacteria (Staphylococcus aureus) and Gram negative bacteria (Pseudomonas aeruginosae and Proteus mirabilis) was observed from the eastern Kenya (Meru) oil. Meru oil was the best and its effectiveness was consistent on nearly all the microbes tested. The oil from the plant growing in the coastal region of Kenya (Mombasa) showed the best effect only on Gram negative bacteria (Escherichia coli and Proteus mirabilis). Both oils (Meru and Mombasa) were dominated by monoterpenes accounting for 92.48 % and 81.37 % respectively. The monoterpene fraction was characterized by a high percentage of eugenol (68.8 %) for Meru oil and 74.10 % for Mombasa oil. The other major monoterpene was methyl eugenol (13.21 %). Camphor (0.95 %) was observed only in the Meru oil. (Cis)-Ocimene, (trans)-ocimene and β-pinene were present in both Meru and Mombasa oils. The sesquiterpenes present in fairly good amounts in both oils were germacrene D and (trans)-caryophyllene. The minor sesquiterpenes were α-farnesene (0.85 %) and β-bisabolene (0.74 %) which were present in the Meru oil only

Preparation of sesquiterpene lactone-loaded pla nanoparticles and evaluation of their antitrypanosomal activity

Human African trypanosomiasis (HAT), also commonly known as sleeping sickness, is a neglected tropical disease affecting millions of people in poorly developed regions in sub-Saharan Africa. There is no satisfactory treatment for this infection. The investment necessary to bring new drugs to the market is a big deterrent to drug development, considering that the affected communities form a non-lucrative sector. However, natural products and many sesquiterpene lactones (STLs) in particular are very strong trypanocides. Research and applications of nano-drug delivery systems such as nanoparticles (NPs) have undergone unprecedented growth in the recent past. This is mainly due to the advantages offered by these systems, such as targeted delivery of the drug to the place of action (cell, parasite, etc), sustained release of the drug, increased bioavailability, reduced drug dosage, and reduction of undesired side effects, among others. In this study, the STLs α-santonin, arglabin, schkuhrin II, vernolepin, and eucannabinolide, all trypanocides, were loaded into polylactic acid (PLA) NPs through an emulsification-diffusion method. The NPs were stable, homogenous, and spherical in shape with a rounded knotty depression like a navel orange. The average particle sizes were 202.3, 220.3, 219.5, 216.9, and 226.4 nm for α-santonin, arglabin, schkuhrin II, vernolepin, and eucannabinolide, respectively. The NPs had encapsulation efficiencies of 94.6, 78.1, 76.8, 60.7, and 78.9% for α-santonin, arglabin, schkuhrin II, vernolepin, and eucannabinolide, respectively. The NPs loaded with arglabin, vernolepin, and eucannabinolide exhibited considerable antitrypanosomal activity against; Trypanosoma brucei rhodesiense (Tbr); with free drug equivalent IC; 50; values of 3.67, 1.11 and 3.32 µM, respectively. None of the NP formulations displayed cytotoxicity towards mammalian cells (rat skeletal myoblast cell line L6). These results provide new insights into the possibility of incorporating STLs into nanoparticles, which may provide new options for their formulation in order to develop new drugs against HAT

Larvicidal activity of metabolites from the endophytic Podospora sp. against the malaria vector Anopheles gambiae

In a screening for natural products with mosquito larvicidal activities, the endophytic fungus Podospora sp. isolated from the plant Laggera alata (Asteraceae) was conspicuous. Two xanthones, sterigmatocystin (1) and secosterigmatocystin (2), and an anthraquinone derivative (3) 13-hydroxyversicolorin B were isolated after fermentation on M2 medium. These compounds were characterised using spectroscopic and X-ray analysis and examined against third instar larvae of Anopheles gambiae. The results demonstrated that compound 1 was the most potent one with LC50 and LC90 values of 13.3 and 73.5 ppm, respectively. Over 95% mortality was observed at a concentration 100 ppm after 24 h. These results compared farvourably with the commercial larvicide pylarvex® that showed 100% mortality at the same concentration. Compound 3 was less potent and had an LC50 of 294.5 ppm and over 95% mortality was achieved at a concentration of 1,000 ppm. Secosterigmatocystin (2) revealed relatively weak activity and therefore LC values were not determined

Chemical composition and antifungal activity of the essential oil from Lippia javanica (Verbenaceae)

Abstract. GC-MS was used in the investigation of the essential oils chemical composition isolated from the leaves of Lippia javanica. A total of 22 components were identified accounting for 76.85% of the oil composition. The oil is characterized by Monoterpenes as shown by the high percentage of Artemisia ketone (49.52%), m-tert-Butylphenol (8.73%), Linalool (4.43%), beta-myrecene (3.13%), Targetone (2.85%) and Isopiperitenone (2.13%). Sesquiterpenes constituted only 6.06% of the total oil. The oil showed inhibitory effects on the visible growth of Fusarium gramenearum while there was no observable activity of the oil against Fusarium moniliforme. The extent of inhibition of visible fungal growth was dependent on the oil concentration. The oil's Minimum Inhibitory Concentration (MIC) value was found to be 27.07 mg/ml. The results obtained shows that the essential oil from L. Javanica can be used to inhibit the growth of phytopathogenic fungi that causes maize diseases in the farms

Heimiomycins A–C and Calamenens from the African Basidiomycete Heimiomyces sp.

Three previously undescribed compounds named heimiomycin A−C (1−3), featuring a unique scaffold with calamenene connected to a hydroxystyryl-pyranone moiety, along with the new calamenene derivatives 4 and 5 and phenanthridine derivative (6) were obtained from a culture of a Heimiomyces sp. This is the first report of the occurrence of calamenene-type terpenoids in fungi. Compound 3 exhibited antimicrobial activity against Gram-positive bacteria and Mucor hiemalis. Compounds 1 and 3 displayed moderate cytotoxicity against KB 3.1 and L929 cell lines, respectively

Two cytotoxic triterpenes from cultures of a Kenyan Laetiporus sp. (Basidiomycota)

HPLC profiling of the mycelial culture of a poroid basidomycete collected in Mount Elgon, Kenya, which probably represents a new species of the genus Laetiporus, led to isolation of two previously undescribed lanostane type triterpenes.We propose the trivial names laetiporins A (1) and B (2). In addition, five known ones: dehydrosulphurenic acid (3), sulphurenic acid (4), eburicoic acid (5), 15α-hydroxytrametenolic acid (6) and trametenolic acid (7) were also isolated. The laetiporins (1–2) exhibited significant cytotoxic effects against various human cancer cells. The known compounds (3–5) and (7) also showed moderate cytotoxic activity, but none of the compounds showed any significant antimicrobial activity

Skeletocutins M–Q: biologically active compounds from the fruiting bodies of the basidiomycete Skeletocutis sp. collected in Africa

During the course of screening for new metabolites from basidiomycetes, we isolated and characterized five previously unde- scribed secondary metabolites, skeletocutins M–Q (1–5), along with the known metabolite tyromycin A (6) from the fruiting bodies of the polypore Skeletocutis sp. The new compounds did not exhibit any antimicrobial, cytotoxic, or nematicidal activities. However, compound 3 moderately inhibited the biofilm formation of Staphylococcus aureus (S. aureus), while compounds 3 and 4 per formed moderately in the ʟ-leucine-7-amido-4-methylcoumarin (ʟ-Leu-AMC) inhibition assay. These compounds represent the first secondary metabolites reported to occur in the fruiting bodies by Skeletocutis. Interestingly, tyromycin A (6) was found to be the only common metabolite in fruiting bodies and mycelial cultures of the fungus, and none of the recently reported skeletocutins from the culture of the same strain were detected in the basidiomes