Chromolaena laevigata (Asteraceae) as a source of endophytic non-aflatoxigenic Aspergillus flavus: chemical profile in different culture conditions and biological applications.

Endophytes are microorganisms that form symbiotic relationships with their host. These microorganisms can produce a variety of secondary metabolites, some of which have inhibitory effects on pests and pathogens or even act to promote plant growth. Due to these characteristics, these microorganisms are used as sources of biologically active substances for a wide range of biotechnological applications. Based on that, the aim of this study was to evaluate the production of metabolites of the endophytic Aspergillus flavus CL7 isolated from Chromolaena laevigata, in four different cultivation conditions, and to determine the antimicrobial, cytotoxic, antiviral, and antioxidant potential of these extracts. The multiphasic approach used to identify this strain was based on morphology and ITS gene sequence analysis. The chemical investigation of A. flavus using potato dextrose and minimal medium, using both stationary and agitated methods, resulted in the isolation of kojic acid, α-cyclopiazonic acid, and 20,25-dihydroxyaflavinine. Another 18 compounds in these extracts were identified by UHPLC-HRMS/MS, of which dideacetyl parasiticolide A has been described for the first time from A. flavus. Aflatoxins, important chemomarkers of A. flavus, were not detected in any of the extracts, thus indicating that the CL7 strain is non-aflatoxigenic. The biological potential of all extracts was evaluated, and the best results were observed for the extract obtained using minimal medium against Trichophyton rubrum and Mycobacterium tuberculosis.

Structural Characterization and Biological Evaluation of 18-Nor-ent-labdane Diterpenoids from Grazielia gaudichaudeana.

The phytochemical investigation of Grazielia gaudichaudeana aerial parts yielded 15 compounds, including diterpenes, triterpenes, sterols and flavonoids. With exception to ent-kaurenoic acid diterpenes, the compounds isolated are being described for the first time in this species. Some unusual 1 H-NMR chemical shifts of 18-nor-ent-labdane (7-9) led us carry out a conformational analysis by theoretical calculations in order to support the experimental data. Moreover, due to the limitation of studies focused on pharmacological potential of Grazielia gaudichaudeana, the present study was carried out to investigate the antioxidant, antiproliferative, antiviral, antileishmanial and antimicrobial activities from the extract, fractions and isolated compounds obtained from this species. Ethyl acetate fraction showed significant activity in the antiproliferative assay, with GI50 range of 3.9 to 27.2 µg mL-1 . Dichloromethane fraction, rich in diterpenoids, inhibited all human tumor cell lines tested, and the nor-labdane 7 showed potent cytotoxic activity against glioma and ovary cancer cell lines.

Evaluation of the antibacterial activity of Piperaceae extracts and nisin on Alicyclobacillus acidoterrestris.

Alicyclobacillus acidoterrestris is a gram-positive aerobic bacterium. This bacterium resists pasteurization temperatures and low pH and is usually involved in the spoilage of juices and acidic drinks. The objective of this study was to evaluate the antibacterial activities of nisin and the species Piper (Piperaceae) on A. acidoterrestris. The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) were determined by the broth microdilution method. The species Piper aduncum had the lowest MIC and an MBC of 15.6 µg/mL and was selected for fractionation. Six fractions were obtained, and the dichloromethane fraction (F.3) had the lowest MIC/MBC (7.81 µg/mL). The dichloromethane fraction was again fractionized, and a spectral analysis revealed that the compound was prenylated chromene (F.3.7). The checkerboard method demonstrated that the crude extract (CE) of P. aduncum plus nisin had a synergistic interaction (fractional inhibitory concentration [FIC] = 0.24). The bactericidal activity of (F.3.7) was confirmed by the time-kill curve. P. aduncum, nisin, and prenylated chromene exhibited strong antibacterial activity against the spores and vegetative cells of A. acidoterrestris. The results of this study suggest that extracts of the genus Piper may provide an alternative to the use of thermal processing for controlling A. spoilage.

Comparative study of the trypanocidal activity of the methyl 1-nitrophenyl-1,2,3,4-9H-tetrahydro-beta-carboline-3-carboxylate derivatives and benznidazole using theoretical calculations and cyclic voltammetry.

The cis and trans isomers of methyl 1-(m-nitro)phenyl and 1-(p-nitro)phenyl-1,2,3,4-tetrahydro-9H-beta-carboline-3-carboxylates (compounds 3a,b, 4a and b) were synthesized and evaluated in vitro against epimastigote forms of Trypanosoma cruzi. Among all of the evaluated tetrahydro-beta-carboline derivatives, the compound trans-methyl 1-(m-nitro)phenyl-1,2,3,4-9H-tetrahydro-beta-carboline-3-carboxylate (3b) was found to exhibit significant trypanocidal activity (IC(50)=22.2 microM). Theoretical studies of molecular conformations and electronic properties for the synthesized compounds and benznidazole, as well as, the cyclic voltammetric (CV) behaviors' determination were performed. A comparative study of the trypanocidal activity of the nitrophenyl-tetrahydro-beta-carbolines derivatives and benznidazole, using the results of theoretical calculations and of the cyclic voltammetry experiments, is presented.