Plant growth regulators and Axl and immune checkpoint inhibitors from the edible mushroom Leucopaxillus giganteus

ABSTRACT

A novel compound, (R)-4-ethoxy-2-hydroxy-4-oxobutanoic acid (1), and six known compounds (2–7) were isolated from the fruiting bodies of the wild edible mushroom Leucopaxillus giganteus. The planar structure of 1 was determined by the interpretation of spectroscopic data analysis. The absolute configuration of 1 was determined by comparing specific rotation of the synthetic compounds. In the plant regulatory assay, the isolated compounds (1–7) and the chemically prepared compounds (8–10) were evaluated their biological activity against the lettuce (Lactuca sativa) growth. Compounds 1 and 3–10 showed the significant regulatory activity of lettuce growth. 1 showed the strongest inhibition activity among the all the compounds tested. In the lung cancer assay, all the compounds were assessed the mRNA expression of Axl and immune checkpoints (PD-L1, PD-L2) in the human A549 alveolar epithelial cell line by RT-PCR. Compounds 1–10 showed significant inhibition activity against Axl and/or immune checkpoint.     

Molecular docking and dynamic simulations of benzimidazoles with beta-tubulins

It is of interest to document the molecular docking and dynamic simulations of benzimidazoles with beta-tubulins in the context of anthelmintic activity. We document the compound BI-02 (2-(3,4-dimethyl phenyl)-1H-1,3-benzimidazole (BI-02) with optimal bindig features compared to the standard molecule albendazole (7.0 Kcal/mol) with binding energy -8.50 Kcal/mol and _PIC₅₀ value 583.62 nM.     

The role of miRNAs as a predictor of multicentricity in breast cancer

Expression profiles of miRNAs are shown to be different in various cancers to regulate expression of mRNA or to have a role in inhibition of translation, thus it shows the possible effect in progression, invasion and metastasis of breast cancer cells. The effect of breast conserving treatment in local recurrence and survival rates for the patients who have multicentric breast cancer is still controversial. In our study, we intended to evaluate the foresight of 84 miRNAs which are identified in breast cancer for having differentiated expressions. Thirty-one patients with unifocal and 26 patients with multicentric breast cancer were included in this study. These tissue samples of both malignant and normal breast tissues were kept in RNA later solution at ??80 °C. Eighty-four miRNAs were studied with miScript miRNA PCR Array Human Breast Cancer kit. Fold change, cut off value was accepted as four. In unifocal group, there were 13 upregulated and five downregulated miRNAs and in multicentric group, there were three upregulated and seven downregulated miRNAs. To reach better results for breast cancer diagnosis and treatment, it is important to enlighten tumor biology, and pay attention to target and individual therapy. Thus, miRNAs have potential role in identifying tumor characteristics in supporting diagnosis and resulting with better evaluated disease for better treatment results with individual strategies.

     

Molecular docking based screening of G6PS with 1, 5 Benzothiazepine derivates for a potential inhibitor

Glucosamine-6-phosphate synthase (G6PS) (EC 2.6.1.16) is a known target for anti-bacterial and anti-fungal infections. Therefore, it is of interest to design potential inhibitors using 1, 5 benzo-thiazepine skeleton with appropriate modifications. We report the binding data for 20 derivatives of the skeleton molecule to G6PS having binding energy from -7.35 to -9.99 Kcal/mol with predicted IC50 value range of 4.11 to 47.68 nano-molar. It should be noted that this data should be further evaluated using in vitro and in vivo studies for safety, activity, efficacy and toxicity.     

Automated synthetic substrate assays for coagulopathies of dogs

Automated synthetic substrate assays for factors II and VII in the extrinsic coagulation pathway have been developed in our laboratory. In both kinetic assays, p-nitroaniline (pNA) was cleaved from the substrate and measured spectrophotometrically at 405 nm. Plasma samples from 5-8 month old beagle dogs were analyzed for factors II and VII, and also for prothrombin times. A subpopulation considered abnormal (prothrombin times greater than 8 seconds) had slightly elevated factor II levels, but extremely low factor VII levels, relative to the normal group. Therefore, the prolonged prothrombin times of this abnormal group can now be confidently attributed to their decreased factor VII levels. The known genetic predisposition of beagle dogs to factor VII deficiency supports this conclusion. Thus, synthetic substrates are useful for the measurement of coagulation factors in dogs, and permit ready automation of the assay.