1,2-Bis[1-(3-methyl­sulfanyl-1,2,4-triazin-5-yl)ethyl­idene]diazane

The mol­ecule of the title compound, C12H14N8S2, has an N—N gauche conformation. The triazine rings are nearly coplanar with respect to the imide bonds [C—C—C—N torsion angles = −15.3 (3) and −15.8 (3)°] and they are twisted by 77.88 (7)°. The overall conformation of the mol­ecule is stabilized by intra­molecular C—H⋯N hydrogen bonding. The mol­ecular packing is influenced by π–π inter­actions of the triazine systems with a shortest centroid–centroid separation of 3.5242 (12) Å

2-(3-Chloro-5,6-diphenyl-2,5-dihydro-1,2,4-triazin-5-yl)-2-methyl­propane­nitrile

The title compound, C19H17ClN4, was obtained from the reaction of 3-chloro-5,6-diphenyl-1,2,4-triazine with isobutyronitrile in the presence of lithium diisopropyl­amide as an unexpected product of covalent addition of isobutyronitrile carbanion to the C-5 atom of the 1,2,4-triazine ring. The 2,5-dihydro-1,2,4-triazine ring is essentially planar (r.m.s. deviation = 0.0059 Å) and the 5- and 6-phenyl substituents are inclined to its mean plane with dihedral angles of 89.97 (4) and 55.52 (5)°, respectively. Intra­molecular C—H⋯N inter­actions occur. In the crystal, mol­ecules related by a c-glide plane are linked into zigzag chains along [001] by N—H⋯N hydrogen bonds

Bioinspired bola-type peptide dendrimers inhibit proliferation and invasiveness of glioblastoma cells in a manner dependent on their structure and amphipathic properties

(1) Background: Natural peptides supporting the innate immune system studied at the functional and mechanistic level are a rich source of innovative compounds for application in human therapy. Increasing evidence indicates that apart from antimicrobial activity, some of them exhibit selective cytotoxicity towards tumor cells. Their cationic, amphipathic structure enables interactions with the negatively-charged membranes of microbial or malignant cells. It can be modeled in 3D by application of dendrimer chemistry. (2) Methods: Here we presented design principles, synthesis and bioactivity of branched peptides constructed from ornithine (Orn) assembled as proline (Pro)- or histidine (His)-rich dendrons and dendrimers of the bola structure. The impact of the structure and amphipathic properties of dendrons/dendrimers on two glioblastoma cell lines U87 and T98G was studied with the application of proliferation, apoptosis and cell migration assays. Cell morphology/cytoskeleton architecture was visualized by immunofluorescence microscopy. (3) Results: Dimerization of dendrons into bola dendrimers enhanced their bioactivity. Pro- and His-functionalized bola dendrimers displayed cytostatic activity, even though differences in the responsiveness of U87 and T98G cells to these compounds indicate that their bioactivity depends not only on multiple positive charge and amphipathic structure but also on cellular phenotype. (4) Conclusion: Ornithine dendrons/dendrimers represent a group of promising anti-tumor agents and the potential tools to study interrelations between drug bioactivity, its chemical properties and tumor cells’ phenotype

5,6,7,8-Tetra­hydro­quinoline 1-oxide hemihydrate

In the title compound, C9H11NO·0.5H2O, the asymmetric unit contains two similar mol­ecules of 5,6,7,8-tetra­hydro­quinoline 1-oxide and one water mol­ecule. The water mol­ecule links the two O atoms of both independent N-oxides into dimers via O—H⋯O hydrogen bonds, forming a three-dimensional network along [101], which is additionally stabilized by weak C—H⋯O inter­molecular inter­actions. In each mol­ecule, the saturated six-membered rings exist in a conformation inter­mediate between a half-chair and sofa

Synthesis, antimicrobial activity and structural studies of low molecular mass lysine dendrimers

Four low molecular mass lysine dendrimers were synthesized by Boc chemistry in solution (155 and 169) and Fmoc chemistry on solid support (P2 and P13). The structure and fragmentation mode of the above dendrimers was investigated in gas phase by the LSI-MS and ESI-MS techniques. 1H and 13C NMR analysis in solution (d6-DMSO) allowed to confirm the correct structure. Antimicrobial activities of the dendrimers against Staphylococcus aureus, Escherichia coli and Candida albicans confirmed our hypothesis that the dendrimer structure can be used for construction of molecules interacting with biological membranes

Natural Antimicrobial Peptides as Inspiration for Design of a New Generation Antifungal Compounds

Invasive fungal infections are associated with high mortality rates, despite appropriate antifungal therapy. Limited therapeutic options, resistance development and the high mortality of invasive fungal infections brought about more concern triggering the search for new compounds capable of interfering with fungal viability and virulence. In this context, peptides gained attention as promising candidates for the antimycotics development. Variety of structural and functional characteristics identified for various natural antifungal peptides makes them excellent starting points for design novel drug candidates. Current review provides a brief overview of natural and synthetic antifungal peptides

Peptide Dendrimers with Non-Symmetric Bola Structure Exert Long Term Effect on Glioblastoma and Neuroblastoma Cell Lines

Background: Glioblastoma (GBM) is the most common malignant tumor of the central nervous system (CNS). Neuroblastoma (NB) is one of the most common cancers of childhood derived from the neural crest cells. The survival rate for patients with GBM and high-risk NB is poor; therefore, novel therapeutic approaches are needed. Increasing evidence suggests a dual role of redox-active compounds in both tumorigenesis and cancer treatment. Therefore, in this study, polyfunctional peptide-based dendrimeric molecules of the bola structure carrying residues with antiproliferative potential on one side and the antioxidant residues on the other side were designed. Methods: We synthesized non-symmetric bola dendrimers and assessed their radical scavenging potency as well as redox capability. The influence of dendrimers on viability of rat primary cerebellar neurons (CGC) and normal human astrocytes (NHA) was determined by propidium iodide staining and cell counting. Cytotoxicity against human GBM cell lines, T98G and LN229, and NB cell line SH-SY5Y was assessed by cell counting and colony forming assay. Results: Testing of CGC and NHA viability allowed to establish a range of optimal dendrimers structure and concentration for further evaluation of their impact on two human GBM and one human NB cell lines. According to ABTS, DPPH, FRAP, and CUPRAC antioxidant tests, the most toxic for normal cells were dendrimers with high charge and an excess of antioxidant residues (Trp and PABA) on both sides of the bola structure. At 5 μM concentration, most of the tested dendrimers neither reduced rat CGC viability below 50–40%, nor harmed human neurons (NHA). The same dose of compounds 16 or 22, after 30 min treatment decreased the number of SH-SY5Y and LN229 cells, but did not affect the number of T98G cells 48 h post treatment. However, either compound significantly reduced the number of colonies formed by SH-SY5Y, LN229, and T98G cells measured 14 days after treatment. Conclusions: Peptide dendrimers with non-symmetric bola structure are excellent scaffolds for design of molecules with pro/antioxidant functionality. Design of molecules with an excess of positive charges and antioxidant residues rendered molecules with high neurotoxicity. Single, 30 min exposition of the GBM and NB cell lines to the selected bola dendrimers significantly suppressed their clonogenic potentia