Synthesis and biological evolution of hydrazones derived from 4-(trifluoromethyl)benzohydrazide

Reflecting the known biological activity of isoniazid-based hydrazones, seventeen hydrazones of 4-(trifluoromethyl)benzohydrazide as their bioisosters were synthesized from various benzaldehydes and aliphatic ketones. The compounds were screened for their in vitro activity against Mycobacterium tuberculosis, nontuberculous mycobacteria (M. avium, M. kansasii), bacterial and fungal strains. The most antimicrobial potent derivatives were also investigated for their cytostatic and cytotoxic properties against three cell lines. Camphor-based molecule, 4-(trifluoromethyl)-N′-(1,7,7-trimethylbicyclo[2.2.1]heptan-2-ylidene)benzohydrazide, exhibited the highest and selective inhibition of M. tuberculosis with the minimum inhibitory concentration (MIC) of 4?µM, while N′-(4-chlorobenzylidene)-4-(trifluoromethyl)benzohydrazide was found to be superior against M. kansasii (MIC?=?16?µM). N′-(5-Chloro-2-hydroxybenzylidene)-4-(trifluoromethyl)benzohydrazide showed the lowest MIC values for gram-positive bacteria including methicillin-resistant Staphylococcus aureus as well as against two fungal strains of Candida glabrata and Trichophyton mentagrophytes within the range of ≤0.49–3.9?µM. The convenient substitution of benzylidene moiety at the position 4 or the presence of 5-chloro-2-hydroxybenzylidene scaffold concomitantly with a sufficient lipophilicity are essential for the noticeable antimicrobial activity. This 5-chlorosalicylidene derivative avoided any cytotoxicity on two mammalian cell cultures (HepG2, BMMΦ) up to the concentration of 100?µM, but it affected the growth of MonoMac6 cells.     

Size of stomata and palisade parenchyma on cotyledon adaxial side in someBrassica oleracea L. varieties

Cotyledons of 15 day-old seedlings of fiveBrassica oleracea L. varieties were surveyed to identify salient anatomical features. Both palisade parenchyma cells present in the first subepidermal layer and stomata were found to differ in size.     

Anatomical characteristics of the epidermis in some cultivars ofBrassica oleracea L. distribution and structure of stomata in the cotyledons

The blade area and the number of stomata were studied in the cotyledons of five cultivars ofBrassica oleracea L., cultivated in a growth chamber and in the greenhouse, respectively. Characteristic differences between different varieties were found in the number of stomata per unit area as well as in their occurrence on both the adaxial and abaxial surfaces.     

Evaluation of potential deer browsing impact on sunflower (<Emphasis Type="Italic">Helianthus annus</Emphasis>)

Large herbivores are the key species for game management in the Central Europe. Analyses of factors affecting the feeding behaviour of herbivores and consequences of their browsing are therefore highly important both for farmers and for game managers as the protective measurements should be focused on the most threatened fields. The influence of fallow (Dama dama) and roe deer (Capreolus capreolus) browsing during vegetation period on sunflower production was studied. The experiment was carried out in 2006 on a field located near a forest complex. We marked out pairs of paired permanent plots and monitored deer impact regularly from the emergence of plants until the harvest. Herbivores damaged the sunflower intensively immediately after the emergence at the height of 1 to 2 cm above the ground. When the plants had reached approximately 15-40 cm in height, deer browsed the top shoots and as the plants grew higher the browsing was restricted to leaves or to substitute stems of the previously browsed plants. Sunflower ceased to attract big herbivores in flowering stage. Browsing significantly affected the yield of seeds. Approximately one half of the plants that had been damaged in early stage died as well as 12.5% of plants that had been damaged at second term; the rest produced substitute stems. Almost 33% of the substitute stems did not form disc florets; the second third of them formed disc florets with a diameter of 6-8 cm, and the last third set disc florets with a diameter of 8-10 cm.     

Synergistic cytotoxicity of perifosine and ABT-737 to colon cancer cells

An acidic environment and hypoxia within the tumour are hallmarks of cancer that contribute to cell resistance to therapy. Deregulation of the PI3K/Akt pathway is common in colon cancer. Numerous Akt-targeted therapies are being developed, the activity of Akt-inhibitors is, however, strongly pH-dependent. Combination therapy thus represents an opportunity to increase their efficacy. In this study, the cytotoxicity of the Akt inhibitor perifosine and the Bcl-2/Bcl-xL inhibitor ABT-737 was tested in colon cancer HT-29 and HCT-116 cells cultured in monolayer or in the form of spheroids. The efficacy of single drugs and their combination was analysed in different tumour-specific environments including acidosis and hypoxia using a series of viability assays. Changes in protein content and distribution were determined by immunoblotting and a “peeling analysis” of immunohistochemical signals. While the cytotoxicity of single agents was influenced by the tumour-specific microenvironment, perifosine and ABT-737 in combination synergistically induced apoptosis in cells cultured in both 2D and 3D independently on pH and oxygen level. Thus, the combined therapy of perifosine and ABT-737 could be considered as a potential treatment strategy for colon cancer.