-
Cell Feb 2022ChRmine, a recently discovered pump-like cation-conducting channelrhodopsin, exhibits puzzling properties (large photocurrents, red-shifted spectrum, and extreme light...
ChRmine, a recently discovered pump-like cation-conducting channelrhodopsin, exhibits puzzling properties (large photocurrents, red-shifted spectrum, and extreme light sensitivity) that have created new opportunities in optogenetics. ChRmine and its homologs function as ion channels but, by primary sequence, more closely resemble ion pump rhodopsins; mechanisms for passive channel conduction in this family have remained mysterious. Here, we present the 2.0 Å resolution cryo-EM structure of ChRmine, revealing architectural features atypical for channelrhodopsins: trimeric assembly, a short transmembrane-helix 3, a twisting extracellular-loop 1, large vestibules within the monomer, and an opening at the trimer interface. We applied this structure to design three proteins (rsChRmine and hsChRmine, conferring further red-shifted and high-speed properties, respectively, and frChRmine, combining faster and more red-shifted performance) suitable for fundamental neuroscience opportunities. These results illuminate the conduction and gating of pump-like channelrhodopsins and point the way toward further structure-guided creation of channelrhodopsins for applications across biology.
Topics: Animals; Channelrhodopsins; Cryoelectron Microscopy; Female; HEK293 Cells; Humans; Ion Channel Gating; Male; Mice, Inbred C57BL; Models, Molecular; Optogenetics; Phylogeny; Rats, Sprague-Dawley; Schiff Bases; Sf9 Cells; Structure-Activity Relationship; Mice; Rats
PubMed: 35114111
DOI: 10.1016/j.cell.2022.01.007 -
IUCrData Jan 2020In the title hydrated Schiff base, CHNO·HO, the dihedral angle between the aromatic rings is 5.06 (11)° and an intra-molecular O-H⋯N hydrogen bond closes an S(6)...
In the title hydrated Schiff base, CHNO·HO, the dihedral angle between the aromatic rings is 5.06 (11)° and an intra-molecular O-H⋯N hydrogen bond closes an S(6) ring. In the crystal, O-H⋯O and O-H⋯N (w = water) hydrogen bonds link the components into centrosymmetric tetra-mers (two Schiff bases and two water mol-ecules). Longer N-H⋯O hydrogen bonds link the tetra-mers into [010] chains. A weak C-H⋯O hydrogen bond and aromatic π-π stacking between the pyrazine and phenyl rings [centroid-centroid separations = 3.604 (2) and 3.715 (2) Å] are also observed.
PubMed: 36337721
DOI: 10.1107/S2414314619017310 -
Metal Ions in Life Sciences Jan 2019The use of metals in medicine has grown impressively in recent years as a result of greatly advanced understanding of biologically active metal complexes and... (Review)
Review
The use of metals in medicine has grown impressively in recent years as a result of greatly advanced understanding of biologically active metal complexes and metal-containing proteins. One landmark in this area was the introduction of cisplatin and related derivatives as anticancer drugs. As the body of literature continues to expand, it is necessary to inspect sub-classes of this group with more acute detail. This chapter will review preclinical research of cobalt complexes coordinated by Schiff base ligands. Cobalt-Schiff base complexes have a wide variety of potential therapeutic functions, including as antimicrobials, anticancer agents, and inhibitors of protein aggregation. While providing a broad introduction to this class of agents, this chapter will pay particular attention to agents for which mechanisms of actions have been studied. Appropriate methods to assess activity of these complexes will be reviewed, and promising preclinical complexes in each of the following therapeutic areas will be highlighted: antimicrobial, antiviral, cancer therapy, and Alzheimer's disease.
Topics: Cobalt; Coordination Complexes; Ligands; Schiff Bases
PubMed: 30855112
DOI: 10.1515/9783110527872-017 -
International Journal of Molecular... Jul 2023As stated by two of the seven papers [...].
As stated by two of the seven papers [...].
Topics: Coordination Complexes; Schiff Bases; Ligands
PubMed: 37446197
DOI: 10.3390/ijms241311014 -
Molecules (Basel, Switzerland) Aug 2019Schiff base, an important family of reaction in click chemistry, has received significant attention in the formation of self-healing hydrogels in recent years. Schiff... (Review)
Review
Schiff base, an important family of reaction in click chemistry, has received significant attention in the formation of self-healing hydrogels in recent years. Schiff base reversibly reacts even in mild conditions, which allows hydrogels with self-healing ability to recover their structures and functions after damages. Moreover, pH-sensitivity of the Schiff base offers the hydrogels response to biologically relevant stimuli. Different types of Schiff base can provide the hydrogels with tunable mechanical properties and chemical stabilities. In this review, we summarized the design and preparation of hydrogels based on various types of Schiff base linkages, as well as the biomedical applications of hydrogels in drug delivery, tissue regeneration, wound healing, tissue adhesives, bioprinting, and biosensors.
Topics: Animals; Click Chemistry; Drug Delivery Systems; Humans; Hydrogels; Schiff Bases; Tissue Adhesives; Wound Healing
PubMed: 31430954
DOI: 10.3390/molecules24163005 -
Molecules (Basel, Switzerland) Apr 2022Chitosan (CS) and its derivatives are receiving considerable attention for their great biocompatibility and broad-spectrum activities in many fields. In this work, we...
Chitosan (CS) and its derivatives are receiving considerable attention for their great biocompatibility and broad-spectrum activities in many fields. In this work, we aimed to characterize the antimicrobial activity of novel chitosan Schiff bases (CSSB). CS was synthesized by double deacetylation of chitin (Cn) after its extraction from the armors of crustaceans , and CSSB-1 and CSSB-2 were synthesized by interaction of CS with 4-(2-chloroethyl) benzaldehyde (aldehyde-1) and 4-(bromoethyl) benzaldehyde (aldehyde-2), respectively, at room temperature. The synthesized compounds were characterized by elemental analysis, gel permeation chromatography (GPC), infrared spectroscopy (FTIR), thermogravimetry (TG), and differential scanning calorimetry (DSC). The antimicrobial activity against Gram-positive () and Gram-negative () bacteria and against yeasts () was significantly increased due to their higher solubility as compared to unmodified CS opening perspectives for the use of these compounds for antimicrobial prevention in different fields as, for example, food industry, cosmetics, or restoration.
Topics: Aldehydes; Anti-Bacterial Agents; Anti-Infective Agents; Benzaldehydes; Chitosan; Microbial Sensitivity Tests; Schiff Bases; Spectroscopy, Fourier Transform Infrared
PubMed: 35566088
DOI: 10.3390/molecules27092740 -
Molecules (Basel, Switzerland) Feb 2022Chemo and siRNA synergic treatments for tumors is a promising new therapeutic trend. Selenocystine, a selenium analog of cysteine, has been considered a potential...
Chemo and siRNA synergic treatments for tumors is a promising new therapeutic trend. Selenocystine, a selenium analog of cysteine, has been considered a potential antitumor agent due to its redox perturbing role. In this study, we developed a nanocarrier for siRNA based on a selenocystine analog engineered polyetherimide and achieved traceable siRNA delivery and the synergic killing of tumor cells. Notably, we applied the label-free Schiff base fluorescence mechanism, which enabled us to trace the siRNA delivery and to monitor the selenocystine analogs' local performance. A novel selenocystine-derived fluorescent Schiff base linker was used to crosslink the polyetherimide, thereby generating a traceable siRNA delivery vehicle with green fluorescence. Moreover, we found that this compound induced tumor cells to undergo senescence. Together with the delivery of a siRNA targeting the anti-apoptotic genes in senescent cells, it achieved a synergistic inhibition function by inducing both senescence and apoptosis of tumor cells. Therefore, this study provides insights into the development of label-free probes, prodrugs, and materials towards the synergic strategies for cancer therapy.
Topics: Cell Line, Tumor; Cell Survival; Cystine; Drug Delivery Systems; Fluorescence; Gene Transfer Techniques; Humans; Microscopy, Fluorescence; Molecular Structure; Nanocomposites; Organoselenium Compounds; RNA, Small Interfering; Schiff Bases
PubMed: 35209090
DOI: 10.3390/molecules27041302 -
Medicinal Chemistry Research : An... 2023Emerging and re-emerging illnesses will probably present a new hazard of infectious diseases and have fostered the urge to research new antiviral agents. Most of the... (Review)
Review
Emerging and re-emerging illnesses will probably present a new hazard of infectious diseases and have fostered the urge to research new antiviral agents. Most of the antiviral agents are analogs of nucleosides and only a few are non-nucleoside antiviral agents. There is quite a less percentage of marketed/clinically approved non-nucleoside antiviral medications. Schiff bases are organic compounds that possess a well-demonstrated profile against cancer, viruses, fungus, and bacteria, as well as in the management of diabetes, chemotherapy-resistant cases, and malarial infections. Schiff bases resemble aldehydes or ketones with an imine/azomethine group instead of a carbonyl ring. Schiff bases have a broad application profile not only in therapeutics/medicine but also in industrial applications. Researchers have synthesized and screened various Schiff base analogs for their antiviral potential. Some of the important heterocyclic compounds like istatin, thiosemicarbazide, quinazoline, quinoyl acetohydrazide, etc. have been used to derive novel Schiff base analogs. Keeping in view the outbreak of viral pandemics and epidemics, this manuscript compiles a review of Schiff base analogs concerning their antiviral properties and structural-activity relationship analysis.
PubMed: 37305208
DOI: 10.1007/s00044-023-03068-0 -
International Journal of Molecular and... 2022Normal drugs exhibit activities against both normal and cancer cells. Furthermore, cancer cells may develop resistance to these drugs that alternative treatment must be...
Normal drugs exhibit activities against both normal and cancer cells. Furthermore, cancer cells may develop resistance to these drugs that alternative treatment must be explored. The main objective of this study was to examine the anticancer activity of Schiff base against Tongue Squamous Cell Carcinoma Fibroblasts (TSCCF) and normal human gingival fibroblasts (NHGF) and to propose its mechanism. A Novel Schiff base ligand was synthesized from the reaction of 5-C-2-4-NABA (5-chloro-2-((4-nitrobenzylidene) amino) benzoic acid). These Schiff bases possessed azomethine group (-HC=N-) and aromatic group (CH) as analyzed by Fourier transforms infrared (FTIR) spectroscopy and UV-Vis spectra. The cytotoxicity screening assay suggested promising activity against TSCCF with IC of 446.68 µg/mL, but insignificant activity against NHGF cells (IC of 977.24 µg/mL) after 72 h. The evidence of apoptotic induction was supported by DAPI staining of apoptotic nuclei with reduced cell numbers, suggesting that Schiff base could induce apoptotic bodies in cancer cells being observed. Based on the Schiff base structure, the anti-cancer mechanism may be attributed to the -HC=N- azomethine group. For the first time, our findings highlighted the anticancer activities of the new Schiff base against oral cancer cell lines.
PubMed: 37727641
DOI: 10.22088/IJMCM.BUMS.11.4.285 -
Molecules (Basel, Switzerland) Jun 2022A mixed-valent trinuclear complex with 1,3-bis(5-chlorosalicylideneamino)-2-propanol (Hclsalpr) was synthesized, and the crystal structure was determined by the...
A mixed-valent trinuclear complex with 1,3-bis(5-chlorosalicylideneamino)-2-propanol (Hclsalpr) was synthesized, and the crystal structure was determined by the single-crystal X-ray diffraction method at 90 K. The molecule is a trinuclear Co-Co-Co complex with octahedral geometries, having a tetradentate chelate of the Schiff-base ligand, bridging acetate, monodentate acetate coordination to each terminal Co ion and four bridging phenoxido-oxygen of two Schiff-base ligands, and two bridging acetate-oxygen atoms for the central Co ion. The electronic spectral feature is consistent with the mixed valent Co-Co-Co. Variable-temperature magnetic susceptibility data could be analyzed by consideration of the axial distortion of the central Co ion with the parameters Δ = -254 cm, = -58 cm, = 0.93, = 0.00436 cm mol, = -0.469 K, = 6.90, and = 2.64, in accordance with a large anisotropy. The cyclic voltammogram showed an irreversible reduction wave at approximately -1.2 V·vs. Fc/Fc, assignable to the reduction of the terminal Co ions.
Topics: 2-Propanol; Acetates; Crystallography, X-Ray; Ligands; Oxygen; Schiff Bases
PubMed: 35807456
DOI: 10.3390/molecules27134211