Lipase‐Catalyzed Kinetic Resolution of Novel Antifungal N‐Substituted Benzimidazole Derivatives

A series of new N‐substituted benzimidazole derivatives was synthesized and their antifungal activity against Candida albicans was evaluated. The chemical step included synthesis of appropriate ketones containing benzimidazole ring, reduction of ketones to the racemic alcohols, and acetylation of alcohols to the esters. All benzimidazole derivatives were obtained with satisfactory yields and in relatively short times. All synthesized compounds exhibit significant antifungal activity against Candida albicans 900028 ATCC (% cell inhibition at 0.25 μg concentration > 98%). Additionally, racemic mixtures of alcohols were separated by lipase‐catalyzed kinetic resolution. In the enzymatic step a transesterification reaction was applied and the influence of a lipase type and solvent on the enantioselectivity of the reaction was studied. The most selective enzymes were Novozyme SP 435 and lipase Amano AK from Pseudomonas fluorescens (E > 100). Chirality 28:347–354, 2016. © 2016 Wiley Periodicals, Inc.     

Haloperidol,but not olanzapine,may affect expression of PER1 and CRY1 genes in human glioblastoma cell line

Background: There is barely any evidence of antipsychotic drugs affecting the molecular clockwork in human, yet it is suggested that clock genes are associated with dopaminergic transmission, i.e. the main target of this therapeutics. We decided to verify if haloperidol and olanzapine affect expression of CLOCK, BMAL1, PER1 and CRY1 in a human central nervous system cell line model. Methods: U-87MG human glioblastoma cell line was used as an experimental model. The cells were incubated with or without haloperidol and olanzapine in the concentration of 5 and 20 μM for 24 h. Real-time quantitative polymerase chain reaction with the ΔC_T analysis was used to examine the effect of haloperidol and olanzapine on the mRNA expression of the genes. Results: At 5 μM, haloperidol decreased expression of CRY1 almost 20-fold. There was nearly a 1.5-fold increase in expression of PER1. Considering the 20 μM haloperidol concentration and both olanzapine concentrations, no other statistically significant effect was observed. Conclusions: At certain concentration, haloperidol seems to affect expression of particular clock genes in a human central nervous system cell line model, yet mechanism underlying this phenomenon remains elusive.     

SOD-Like Activity of Copper(II) Containing Metallopeptides Branched By 2,3-Diaminopropionic Acid: What the N-Termini Elevate,the C-Terminus Ruins

International Journal of Peptide Research and Therapeutics - Relations between structural modifiactions and SOD-like activity of four branched CuII-metallopeptides based on l-2,3-diaminopropionic...     

Determination of roxithromycin in human plasma by HPLC with fluorescence and UV absorbance detection: application to a pharmacokinetic study

A selective HPLC method with fluorescence detection for the determination of roxithromycin (ROX) in human plasma was described. After solid-phase extraction (SPE), ROX and erythromycin (internal standard, I.S.) were derivatized by treatment with 9-fluorenylmethyl chloroformate (FMOC-Cl). Optimal resolution of fluorescence derivatives of ROX and I.S. was obtained during one analytical run using reversed phase, C(18) column. The mobile phase was composed of potassium dihydrogenphosphate solution, pH 7.5 and acetonitrile. Fluorescence of the compounds was measured at the maximum excitation, 255 nm and emission, 313 nm, of ROX derivatives. Validation parameters of the method were also established. After SPE, differences in recoveries of ROX and erythromycin from human plasma were observed. The linear range of the standard curve of ROX in plasma was 0.5-10.0 mg/l. The validated method was successfully applied for pharmacokinetic studies of ROX after administration of a single tablet of ROX.     

Dose- and time-dependent alterations in lipid metabolism after pharmacological PGC-1α activation in L6 myotubes

Pyrroloquinoline quinone (PQQ) acts as a powerful modulator of PGC-1α activation and therefore regulates multiple pathways involved in cellular energy homeostasis. In the present study, we assessed the effects of L6 myotubes incubation with 0.5, 1, and 3 μM PQQ solution for 2 and 24 hr with respect to the cells' lipid metabolism. We demonstrated that PQQ significantly elevates PGC-1α content in a dose- and time-dependent manner with the highest efficiency for 0.5 and 1 µM. The level of free fatty acids was diminished (24 hr: −66%), while an increase in triacylglycerol (TAG) amount was most pronounced after 0.5 μM (2 hr: +93%, 24 hr: +139%) treatment. Ceramide (CER) content was elevated after 2 hr incubation with 0.5 µM and after prolonged exposure to all PQQ concentrations. The cells treated with PQQ for 2 hr exhibited decreased sphinganine (SFA) and sphinganine-1-phosphate (SFA1P) level, while 24 hr incubation resulted in an elevated sphingosine (SFO) amount. In summary, PGC-1α activation promotes TAG and CER synthesis.     

Can a stench be beautiful? – Osmophores in stem-succulent stapeliads (Apocynaceae-Asclepiadoideae-Ceropegieae-Stapeliinae)

Carrion flower stapeliads are examples of olfactory mimicry, forming sapromyiophilous flowers, which mimic food sources or oviposition sites to attract fly pollinators. The aim of this work was to investigate the ultrastructure of osmophores involved in the release of the carrion odor of Orbea variegata and Boucerosia indica flowers. In spite of their similar architecture (epidermal epithelium+subepidermal secretory layers), the osmophores of stapeliads feature some differences in morphology and ultrastructure. The epidermal epithelial cells of O. variegata and B. indica differ in shape, but both are extremely rich in endoplasmic reticulum and flocculent material in the vacuole. Unlike the Orbea, Boucerosia has starchless leucoplasts in the epidermal epithelium. Orbea features a cuticle with microchannels, while Boucerosia has a different mechanism for the pathway of scent substances to the cell exterior. They are released by rupturing of the outer layer of cuticle at the apex of the papillae. The epidermal cells of the adaxial corolla differ even between parts of the corolla, the corolla lobes and the annulus in the flower. This diversity may be connected with an odor gradient. The morphological and anatomical features of stapeliad (subtribe Stapeliinae) osmophores are generally similar to osmophores of members of subtribe Ceropegiinae (Ceropegia), thus, we suggest that this model of osmophores evolved before early diversification of Ceropegieae. The ultrastructural features of stapeliad osmophores are generally similar to those of Araceae, Orchidaceae and Passifloraceae.     

Foliar characteristics,cambial activity and wood formation in Azadirachta indica A. Juss. as affected by coal–smoke pollution

This study, aimed at elucidating changes in the foliar and cambial behavior in Azadirachta indica (Neem tree) due to coal-smoke pollution, has revealed inhibitory effects of pollution stress on leaf pigments concentrations, nitrate reductase activity and the contents of reducing sugars and total N content, whereas stimulatory effects were given on stomatal index and nitrate and sulphur contents. Under smoke effects, stomatal conductance was low, leading to a drop in the net photosynthetic rate and a rise in the internal CO₂ concentration of leaf. Cambial reactivation in the stem was delayed at the polluted site. Although the total span of the cambial activity was reduced, greater amount of wood was observed to accumulate in the stem axis under heavy pollution stress. Vessel proportion in the wood increased, whereas size of vessel elements and xylem fibers decreased. “Vulnerability factor” (ratio between mean vessel diameter and mean vessel abundance) and “mesomorphic ratio” (multiplication product of vulnerability factor and mean length of vessel element) of the stem–wood, both declined with increase in the pollution stress, thus indicating a tendency of the species for shifting towards xeromorphy when grown under stress. Given the opposite trends of photosynthetic rate and wood increment, the carbon-partitioning pattern rather than the photosynthetic rate seems to have influenced the accumulation of new wood. The Neem tree proves to be suitable for growing in the polluted areas.     

Micro‐ and nano‐scale ultrastructure of cell walls in Cryogenian microfossils: revealing their biological affinity

Moczyd?owska, M., Schopf, J.W. & Willman, S. 2009: Micro‐ and nano‐scale ultrastructure of cell walls in Cryogenian microfossils: revealing their biological affinity. Lethaia, Vol. 43, pp. 129–136. Recently established protocols and methods in advanced microscopy and spectrometry applied to studies of ancient unicellular organic‐walled microfossils of uncertain biological affinities (acritarchs) provide new evidence of the fine ultrastructure of cell walls and their biochemistry that support the interpretation of some such microfossils as photosynthesizing microalgae. The micro‐scale and nanoscale ultrastructure of the cell walls of late Cryogenian sphaeromorphic acritarchs from the Chichkan Formation (Kazakhstan) revealed by the advanced techniques and studied originally by Kempe et al. (2005) is here further analysed and compared with that of modern microalgal analogues. On the basis of such comparison, we interpret the preserved cell wall ultrastructure to reflect original layering and lamination within sub‐layers of the fossil wall, rather than being a result of taphonomic and diagenetic alteration. The outer thick layer represents the primary wall and the inner layer the secondary wall of the cell, whereas the laminated amorphous sub‐layers, 10–20 nm in thickness and revealed by transmission electron and atomic force microscopy, are recognized as trilaminar sheath structure. Because two‐layered cell walls, trilaminar sheaths and the position of the TLS within the fossil cell wall are characteristic of the mature developmental state in cyst morphogenesis in modern microalgae, we infer that the Chichkan sphaeromorphs are probably resting cells (aplanospores) of chlorophyceaen green microalgae from the order Volvocales. □Biological affinity, cell wall, Cryogenian, microfossils, ultrastructure.