Structure, bioactivity and synthesis of natural products with hexahydropyrrolo[2,3-b]indole

Research on natural products containing hexahydropyrrolo[2,3-b]indole (HPI) has dramatically increased during the past few years. Newly discovered natural products with complex structures and important biological activities have recently been isolated and synthesized. This review summarizes the structures, biological activities, and synthetic routes for natural compounds containing HPI, emphasizing the different strategies for assembling this motif. It covers a broad gamut of molecules, from small alkaloids to complex peptides

Intelligent system in the context of business process modelling

The article deals with the features and characteristics of intelligent systems for modelling business processes. Their classification was made and criteria for comparison were developed. According to the comparative analysis of existing expert systems for intelligent analysis, a reasonable choice of system for modelling business processes of a particular enterprise has been carried out. In general, it was found that the introduction of intelligent systems for modelling business processes of the enterprise and forecasting its activities for future allows management of the company to obtain relevant and necessary information for the adoption of effective management decisions and the development of a strategic pla

Canine Retina Has a Primate Fovea-Like Bouquet of Cone Photoreceptors Which Is Affected by Inherited Macular Degenerations

Retinal areas of specialization confer vertebrates with the ability to scrutinize corresponding regions of their visual field with greater resolution. A highly specialized area found in haplorhine primates (including humans) is the fovea centralis which is defined by a high density of cone photoreceptors connected individually to interneurons, and retinal ganglion cells (RGCs) that are offset to form a pit lacking retinal capillaries and inner retinal neurons at its center. In dogs, a local increase in RGC density is found in a topographically comparable retinal area defined as the area centralis. While the canine retina is devoid of a foveal pit, no detailed examination of the photoreceptors within the area centralis has been reported. Using both in vivo and ex vivo imaging, we identified a retinal region with a primate fovea-like cone photoreceptor density but without the excavation of the inner retina. Similar anatomical structure observed in rare human subjects has been named fovea-plana. In addition, dogs with mutations in two different genes, that cause macular degeneration in humans, developed earliest disease at the newly-identified canine fovea-like area. Our results challenge the dogma that within the phylogenetic tree of mammals, haplorhine primates with a fovea are the sole lineage in which the retina has a central bouquet of cones. Furthermore, a predilection for naturally-occurring retinal degenerations to alter this cone-enriched area fills the void for a clinically-relevant animal model of human macular degenerations

Structure, bioactivity and synthesis of natural products with hexahydropyrrolo[2,3-b]indole

Research on natural products containing hexahydropyrrolo[2,3-b]indole (HPI) has dramatically increased during the past few years. Newly discovered natural products with complex structures and important biological activities have recently been isolated and synthesized. This review summarizes the structures, biological activities, and synthetic routes for natural compounds containing HPI, emphasizing the different strategies for assembling this motif. It covers a broad gamut of molecules, from small alkaloids to complex peptides

Orthogonal protecting groups in the synthesis of tryptophanyl-hexahydropyrroloindoles

The synthesis of various polycyclic systems containing a C3a-Ni bond between a hexahydropyrrolo[2,3-b]indole and an indole tryptophan is described here. A series of experiments were performed to determine the best combination of five orthogonal protecting groups and the best reaction conditions for formation of said bond, which is a common feature among many recently discovered marine natural products

Oligo (Poly(Ethylene Glycol)Fumarate)-Based Multicomponent Cryogels for Neural Tissue Replacement

Synthetic hydrogels provide a promising platform to produce neural tissue analogs with improved control over structural, physical, and chemical properties. In this study, oligo (poly (ethylene glycol) fumarate) (OPF)-based macroporous cryogels were developed as a potential next-generation alternative to a non-porous OPF hydrogel previously proposed as an advanced biodegradable scaffold for spinal cord repair. A series of OPF cryogel conduits in combination with PEG diacrylate and 2-(methacryloyloxy) ethyl-trimethylammonium chloride (MAETAC) cationic monomers were synthesized and characterized. The contribution of each component to viscoelastic and hydration behaviors and porous structure was identified, and concentration relationships for these properties were revealed. The rheological properties of the materials corresponded to those of neural tissues and scaffolds, according to the reviewed data. A comparative assessment of adhesion, migration, and proliferation of neuronal cells in multicomponent cryogels was carried out to optimize cell-supporting characteristics. The results show that OPF-based cryogels can be used as a tunable synthetic scaffold for neural tissue repair with advantages over their hydrogel counterparts

New 2-Ethylthio-4-methylaminoquinazoline derivatives inhibiting two subunits of cytochrome bc1 in Mycobacterium tuberculosis

The emergence of multi-drug (MDR-TB) and extensively-drug resistant tuberculosis (XDR-TB) is a major threat to the global management of tuberculosis (TB) worldwide. New chemical entities are of need to treat drug-resistant TB. In this study, the mode of action of new, potent quinazoline derivatives was investigated against Mycobacterium tuberculosis (M. tb). Four derivatives 11626141, 11626142, 11626252 and 11726148 showed good activity (MIC ranging from 0.02-0.09 mu g/mL) and low toxicity (TD50 >= 5 mu g/mL) in vitro against M. tb strain H37Rv and HepG2 cells, respectively. 11626252 was the most selective compound from this series. Quinazoline derivatives were found to target cytochrome bc(1) by whole-genome sequencing of mutants selected with 11626142. Two resistant mutants harboured the transversion T943G (Trp312Gly) and the transition G523A (Gly175Ser) in the cytochrome bc(1) complex cytochrome b subunit (QcrB). Interestingly, a third mutant QuinR-M1 contained a mutation in the Rieske iron-sulphur protein (QcrA) leading to resistance to quinazoline and other QcrB inhibitors, the first report of cross-resistance involving QcrA. Modelling of both QcrA and QcrB revealed that all three resistance mutations are located in the stigmatellin pocket, as previously observed for other QcrB inhibitors such as Q203, AX-35, and lansoprazole sulfide (LPZs). Further analysis of the mode of action in vitro revealed that 11626252 exposure leads to ATP depletion, a decrease in the oxygen consumption rate and also overexpression of the cytochrome bd oxidase in M. tb. Our findings suggest that quinazoline-derived compounds are a new and attractive chemical entity for M. tb drug development targeting two separate subunits of the cytochrome bc(1) complex

Non-invasive topical drug delivery to spinal cord with carboxyl-modified trifunctional copolymer of ethylene oxide and propylene oxide

In this study the effect of oxidative modification on micellar and drug deliveryproperties of copolymers of ethylene oxide (EO) and propylene oxide (PO) wasinvestigated. Carboxylated trifunctional copolymers were synthesized in the reaction withchromium oxide (VI). We found that carboxylation significantly improved the uniformityand stability of polymeric micelles by inhibiting the microphase transition. Thecytotoxicity of copolymers was studied in relation to their aggregative state on two celltypes (cancer line vs. primary fibroblasts). The accumulation of rhodamine 123 inneuroblastoma SH-SY5Y cells was dramatically increased in the presence of the oxidizedblock copolymer with the number of PO and EO units of 83.5 and 24.2, respectively. Thecopolymer was also tested as an enhancer for topical drug delivery to the spinal cordwhen applied subdurally. The oxidized copolymer facilitated the penetration ofrhodamine 123 across spinal cord tissues and increased its intraspinal accumulation.These results show the potential of using oxidized EO/PO based polymers for noninvasivedelivery of protective drugs after spinal cord injury