Myrothecium verrucaria grown on a large scale (760 L) has yielded a variety of new trichothecenes including the nonmacrocyclic trichoverroids 13-19, which contain a pendant C4 cis,trans-dienic ester side chain normally common only to the macrocyclic roridins and verrucarins. Several novel macrocyclic trichothecenes (roridins J and K acetate) and verrucarins L and L acetate also were isolated and characterized.The trichothecene complex of antibiotics has generated due to the wide spectrum of biological activity exhibited a great deal of interest during the past 10 years, principally by these sesquiterpene mycotoxins.

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Albizia schimperianaOliv. (Leguminosae) is a tree distributed in the highland of Kenya, where it is used as a traditional medicine for the treatment of bacterial and parasitic infections, notably pneumonia and malaria, respectively. Bioassay guided isolation of the CH2Cl2–MeOH 1:1/MeOH-H2O 9:1 (mixed) extract of A. schimperiana afforded the new bioactive macrocyclic spermine alkaloid, namely 5,14-dimethylbudmunchiamine L1 1 and three known budmunchiamine analogs 2-4. The structures of the compounds 1-4 were determined by 1D and 2D NMR data, including COSY, HMQC, and HMBC experiments, and ESI-HRMS. Compounds 1 and 3 exhibited significant in vitro antimicrobial activity against a panel of microorganisms, including C. neoformans, methicillin-resistant S. aureus, E. coli, M. intracellulare, A. fumigatus. In addition, they demonstrated strong in vitro antimalarial activities against chloroquine-susceptible (D6) and -resistant (W2) strains of Plasmodium falciparum with IC50s ranging from 120–270 ng/mL. Compounds 1-4 were also evaluated for cytotoxic activity against selected human cancer cell lines and mammalian kidney fibroblasts (VERO cells). It was observed that hydroxyl substitution of the side chain of the budmunchiamines dramatically reduced the cytotoxicity and antimicrobial activity of the alkaloids 2 and 4 without decreasing antimalarial activity.

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A previous study on the feeding responses of tsetse flies, Glossina morsitans morsitans, implicated the existence of allomonal barriers, both volatile and nonvolatile, on the nonpreferred host, waterbuck, Kobus defassa. In the present study, electroantennogram-active compounds in odors from waterbuck were compared with those of two preferred hosts of tsetse flies, buffalo, Syncerus caffer, and ox, Bos indicus. Odors from the three bovids were trapped on activated charcoal and/or reverse-phase (octadecyl bonded) silica and analyzed with a gas chromatography-linked electroantennographic detector (GC-EAD) and, where possible, identified by using gas chromatography-linked mass spectrometry (GC-MS) and chromatographic comparisons with authentic samples. The GC-EAD profiles (with G. m. morsitans antennae) of the odors of the two preferred hosts were comparable, comprising medium-chain, saturated or unsaturated aldehydes and phenols, with buffalo emitting a few more EAG-active aldehydes. Waterbuck odor gave a richer profile, consisting of fewer aldehydes but more phenolic components and a series of 2-ketones (C-C13) and delta-octalactone. This bovid also emits moderate amounts of C5-C9 straight-chain fatty acids, some of which were detected in buffalo and ox only in trace amounts. However, these did not elicit significant GC-EAD responses. Waterbuck profiles from the antennae of G. pallidipes showed broad similarity to those from G. m. morsitans, although the composition of aldehydes and ketones was somewhat different, indicating species-specific difference in the detection of host odors. Certain waterbuck-specific EAG-active components, particularly the 2-ketones and lactone, constitute a candidate allomonal blend in waterbuck odor.

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.