Essential oil composition and in vitro antibacterial activity of Chenopodium album subsp. striatum.

The objective of this study was to identify the bioactive compounds of essential oil and evaluate the antibacterial activity of the essential oil extracted from Chenopodium album subsp. striatum against multidrug-resistant bacterial strains (MDR) which were isolated from clinical specimens by conventional methods. Furthermore, eight different Gram-negative and Gram-positive multidrug-resistant bacterial strains were used to investigate the antibacterial potential of the essential oil. The antibacterial activity was tested using MIC and MBC microdilution method, well and disc diffusion in different concentration. The hydro-distillation of aerial parts powder yield was 0.466% (v/w). Essential oil showed bactericidal activity against both MDR Gram-negative and Gram-positive bacterial strains. MIC and MBC results were ranged from 0.31 to 2.5 and 0.62 to 5.0 mg/mL. The inhibition zones in well-diffusion method were ranged from 7 ± 0.6 mm to 15 ± 1.0 mm. Disc diffusion method was ranged from 7 ± 0.0 mm to 16 ± 0.6 mm depending on the type of bacteria strain and essential oil concentration. Essential oil of Ch. album had the greatest potential to be considered as an antibacterial agent against MDR bacteria strain. This potential was due to different biological and bioactive compounds like phytol, linalool, α-terpineol and linolenic acid in the plant.

Bioassay-directed isolation of quaternary benzylisoquinolines from Berberis integerrima with bactericidal activity against Brucella abortus.

Berberis integerrima Bonge. (Syn: Berberis densiflora Boiss. & Buhse) is a shrub widely distributed in Middle East and central part of Asia. An ethnobotanical study revealed that indigenous and tribal people in Iran use B. integerrima root decoction for treatment of brucellosis. Therefore, the aim of this study was bioassay directed isolation of antibacterial compounds from this plant based on their in vitro bactericidal activity against Brucella abortus. Briefly, the ethanol extract of B. integerrima was fractioned and subjected to preliminary antibacterial screening tests against Brucella. The more active fraction (Fr.3) was subjected to purification by repeated chromatography systems. Quaternary benzylisoquinoline alkaloids including columbamine, palmatine, berberine, and jatrorhizine were four main components identified in the selected active fraction. Except for berberine which is reported before, palmatine, columbamine and jatrorhizine are isolated for the first time from this plant. Anti-brucellosis properties of isolated compounds 1-4 were studied against B. abortus under different test conditions. In minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) results, jatrorhizine (4) showed more antibacterial activity with MIC and MBC of 0.78 and 1.56 µg/mL, respectively. In both agar well diffusion and disk diffusion ANOVA results showed that there were statistically significant differences between compounds 1-4 versus placebo in all of the tested concentration (P <0.001). In conclusion, all of four alkaloids showed potent antibacterial activity against B. abortus but jatrorhizine and columbamine with free hydroxyl group on C-3 or C-2 showed more activity than palmatine and berberine without any free hydroxyl group on their structures. The antibacterial effects of columbamine (15 µg/mL) and jatrorhizine (15 µg/mL) were comparative to streptomycin (10 µg/mL) as standard drug which candidate them for more pharmacological researches to find new antibacterial agents against brucellosis.

Anti-ROR1 scFv-EndoG as a Novel Anti-Cancer Therapeutic Drug

Aim: Immunotoxins are proteins that consist of an antibody fragment linked to a toxin, used as agents for targeted therapy of cancers. Although the most potent immunotoxins are made from bacterial and plant toxins, obstacles which contribute to poor responses are immunogenicity in patients and rapid development of neutralizing antibodies. In the present study we proposed a new therapeutic immunotoxin for targeted cancer therapy of ROR1 expressing cancers: an anti ROR1 single chain fragment variable antibody (scFv)-endonuclease G (anti ROR1 scFv-EndoG). Methods: The three-dimensional structure of anti ROR1 scFv-EndoG protein was modeled and structure validation tools were employed to confirm the accuracy and reliability of the developed model. In addition, stability and integrity of the model were assessed by molecular dynamic (MD) simulation. Results: All results suggested the protein model to be acceptable and of good quality. Conclusions: Anti-ROR1 scFv-EndoG would be expected to bind to the ROR1 extracellular domain by its scFv portion and selectively deliver non-immunogenic human endonuclease G enzyme as an end-stage apoptosis molecule into ROR1-expressing cancer cells and lead rapidly to apoptosis. We believe that anti ROR1 and other anti-tumor antigen scFv-EndoG forms may be helpful for cancer therapy.

ScFv Improvement Approaches.

The most common recombinant antibody format is the single chain fragment variable (scFv) which it contains the complete antigen-binding domains of an intact antibody. ScFv fragments have found vast medical and non-medical applications. Several approaches have been employed to increase the affinity, avidity and structural stability related to these antibody fragments. Most approaches related to scFv improvement have been included in this review.