Synthesis, characterization and biological evaluation of two cyclometalated iridium(III) complexes containing a glutathione S-transferase inhibitor.

The cyclometalated iridium(III) compounds have been intensively studied for health-related applications due to their outstanding luminescent properties and multiple anticancer modes of action. Herein, two iridium(III) compounds Ir-1 and Ir-3 containing glutathione S-transferase inhibitor (GSTi) were developed and studied together with two unfunctionalized compounds Ir-2 and Ir-4 as a comparison. Biological study indicated that GSTi-bearing complexes Ir-1 and Ir-3 exert a synergistic effect on the inhibition of cancer cells. The photophysical properties of Ir-1 âˆ¼ Ir-4 were investigated by UV/vis absorption and fluorescence spectroscopy and rationalized with TD-DFT calculations. As expected, GSTi-bearing complexes Ir-1 and Ir-3 exhibited considerable cytotoxicity against both A549 and cisplatin-resistant A549/cis cancer cells, much higher than the unfunctionalized iridium compounds Ir-2 and Ir-4. Further study indicated that Ir-1 and Ir-3 mainly localize in the mitochondria of tumor cells, and exert their cytotoxicity via generating ROS and inhibiting GST activity. The flow cytometry investigations demonstrated that Ir-1 and Ir-3 can arrest the cell cycle in S phase and induce the cell death through apoptosis process. Overall, the complexation of GST inhibitors with cyclometalated iridium(III) agents provides an effective way for potentiating the cytotoxicity of iridium(III) anticancer agents and resensitizing the efficacy against cisplatin resistant cancer cells.

Multifunctional platinum(IV) complex bearing HDAC inhibitor and biotin moiety exhibits prominent cytotoxicity and tumor-targeting ability.

Despite the wide clinical use of platinum drugs in cancer treatment, their severe side effects and lack of tumor selectivity seriously limit their further clinical application. To address the limitations of the current platinum drugs, herein a multifunctional platinum(IV) compound 1 containing a histone deacetylase (HDAC) inhibitor (4-phenylbutyric acid, 4-PBA) and a tumor-targeting group (biotin) has been designed and prepared. An in vitro cytotoxicity study indicated that compound 1 exhibits comparable or superior cytotoxicity to cisplatin against the tested cancer cell lines, but greatly reduced toxicity in human normal liver LO2 cells, implying the potential tumor-targeting ability of compound 1. Molecular docking results indicate that compound 1 can effectively interact with a biotin-specific receptor (streptavidin) through its biotin moiety, enabling potential tumor-targeting capability. Further studies indicated that compound 1's cytotoxicity stems from inducing DNA damage via the mitochondrial apoptotic pathway and inhibiting HDACs. Consequently, this compound can not only take advantage of the tumor selectively of biotin to improve its tumor-targeting ability but also strengthen its anticancer activity via simultaneously targeting DNA and HDACs.

Surface modification of BiOBr/TiO2 by reduced AgBr for solar-driven PAHs degradation: Mechanism insight and application assessment.

A novel solar active AgBr/BiOBr/TiO2 catalyst was synthesized by a facile coprecipitation method for solar-driven water remediation. The synthesized material composed of flower-like TiO2 nanoparticles loaded on BiOBr nanosheets and with homogeneous surface distributed Ag/AgBr nanoparticles. The internal electric field between BiOBr/TiO2 heterojunction greatly facilitated the charge carrier migration; the introduction of narrow band gap semiconductors (AgBr and BiOBr) promoted the visible light adsorption; and the Ag/AgBr nanoparticles acted as photosensitizer to further improve the light utilization. The new material showed 7.6- and 4.0-times activity of pure TiO2 and BiOBr under solar light, and the contribution of reactive species on anthracene degradation followed the order of h+ >O2•-> •OH. The degradation mechanism and pathway were proposed based on intermediates analysis and DFT calculation. The QSAR analysis revealed that the environmental risks of contaminants were greatly reduced during the photocatalysis process but some intermediates were still toxic. The high photocatalytic activity, stability and adaptability all indicated that this new material owns great application potential for cost-effective photocatalytic remediation of persistent organic contaminants under solar light.

Host defense peptides in skin secretions of Odorrana tiannanensis: Proof for other survival strategy of the frog than merely anti-microbial.

Genus Odorrana, among all amphibians studied, is generally reported to have the most abundant and diversified anti-microbial peptides even from a single individual frog. In our previous work, 46 cDNA sequences encoding precursors of 22 different anti-microbial peptides (AMPs) were characterized from the skin of frog, Odorrana tiannanensis. In this work, we reported the purification of three AMPs from skin secretions of O. tiannanensis. Their amino acid sequences matched well with the sequences deduced from cDNAs and they were designated as Odorranain-C7HSa, Brevinin-1-OT2 and Odorranain-G-OT, respectively. Furthermore, we selected to analyze the four most structurally diversified sequences among the 22 AMPs that are significantly different from all reported AMPs. By structural characterization, three of them were designated as pleurain-E-OT, odorranain-G-OT, odorranain-A-OT, belonging to AMP families already identified. The forth one with a unique 14-mer sequence of AILTTLANWARKFLa and C-terminal amidation represents the prototypes of a new class of amphibian AMP, and thereby named tiannanensin. Such broad diversity in sequences and structures are consistent with other species in Genus Odorrana. Multi-functions of the synthesized four special AMPs were screened, including anti-microbial, antioxidant, cytotoxic and hemolytic activities. The results suggest that these AMPs may employ sophisticated mechanisms of action in host defense in addition to anti-microbial, although their precise contribution to host defense still seems unclear.

Gene cloning, expression and characterization of avian cathelicidin orthologs, Cc-CATHs, from Coturnix coturnix.

Cathelicidins comprise a family of antimicrobial peptides sharing a highly conserved cathelin domain, which play a central role in the early innate host defense against infection. In the present study, we report three novel avian cathelicidin orthologs cloned from a constructed spleen cDNA library of Coturnix coturnix, using a nested-PCR-based cloning strategy. Three coding sequences containing ORFs of 447, 465 and 456 bp encode three mature antimicrobial peptides (named Cc-CATH1, 2 and 3) of 26, 32 and 29 amino acid residues, respectively. Phylogenetic analysis indicated that precursors of Cc-CATHs are significantly conserved with known avian cathelicidins. Synthetic Cc-CATH2 and 3 displayed broad and potent antimicrobial activity against most of the 41 strains of bacteria and fungi tested, especially the clinically isolated drug-resistant strains, with minimum inhibitory concentration values in the range 0.3-2.5 µm for most strains with or without the presence of 100 mm NaCl. Cc-CATH2 and 3 showed considerable reduction of cytotoxic activity compared to other avian cathelicidins, with average IC(50) values of 20.18 and 17.16 µm, respectively. They also exerted a negligible hemolytic activity against human erythrocytes, lysing only 3.6% of erythrocytes at a dose up to 100 µg·mL(-1) . As expected, the recombinant Cc-CATH2 (rCc-CATH2) also showed potent bactericidal activity. All these features of Cc-CATHs encourage further studies aiming to estimate their therapeutic potential as drug leads, as well as coping with current widespread antibiotic resistance, especially the new prevalent and dangerous 'superbug' that is resistant to almost all antibiotics.

Gene cloning and characterization of novel antinociceptive peptide from the brain of the frog, Odorrana grahami.

Amphibian opiate peptides including dermorphins and deltorpins have been recently found only in the skin of South American frogs belonging to the subfamily Phyllomedusinae (Phyllomedusa, Agalychnis and Pachymedusa species). No opiate peptides have ever been identified from other amphibians or organs except skin. Here we report the purification and characterization of a novel antinociceptive peptide named odorranaopin from the homogenates of the frog brains, Odorrana grahami, which is also the first antinociceptive peptide found in Ranidae amphibian. Odorranaopin comprises 17 amino acid residues with the sequence of DYTIRTRLHQESSRKVL (Mr 2102 Da). The cDNA encoding odorranaopin was cloned from the frog brain cDNA library, and it was confirmed to be a specific gene. The odorranaopin precursor deduced is composed of 61 amino acid residues including the predicted signal peptide, acidic spacer peptide and mature odorranaopin positioned at the C-terminus. Odorranaopin could inhibit nociceptive responses induced by formalin and acetic acid. It also inhibited the contractile responses of ileum smooth muscle induced by bradykinin, implying that the antinociceptive activity of odorranaopin possibly results from its blockade on bradykinin or bradykinin receptor functions. Odorranaopin is the first antinociceptive peptide found in Ranidae amphibian.

Molecular cloning and characterization of novel cathelicidin-derived myeloid antimicrobial peptide from Phasianus colchicus.

Cathelicidins were initially characterized as a family of antimicrobial peptides. Now it is clear that they fulfill several immune functions in addition to their antimicrobial activity. In the current work, three cDNA sequences encoding pheasant cathelicidins were cloned from a constructed bone marrow cDNA library of Phasianus colchicus, using a nested-PCR-based cloning strategy. The three deduced mature antimicrobial peptides, Pc-CATH1, 2 and 3 are composed of 26, 32, and 29 amino acid residues, respectively. Unlike the mammalian cathelicidins that are highly divergent even within the same genus, Pc-CATHs are remarkably conserved with chicken fowlicidins with only a few of residues mutated according to the phylogenetic analysis result. Synthetic Pc-CATH1 exerted strong antimicrobial activity against most of bacteria and fungi tested, including the clinically isolated (IS) drug-resistant strains. Most MIC values against Gram-positive bacteria were in the range of 0.09-2.95 µM in the presence of 100mM NaCl. Pc-CATH1 displayed a negligible hemolytic activity against human erythrocytes, lysing 3.6% of erythrocytes at 3.15 µM (10 µg/ml), significantly higher than the corresponding MIC. Pc-CATH1 was stable in the human serum for up to 72 h, revealing its extraordinary serum stability. These specific features of Pc-CATH1 may make its applications much wider given the potency and breadth of the peptide's bacteriocidal capacity and its resistance towards serum and high-salt environments.

Non-Bragg resonance of surface water waves in a trough with periodic walls.

The non-Bragg resonance of surface water waves is investigated, both theoretically and experimentally, in a trough with square-wave corrugated sidewalls. Unlike the familiar Bragg resonances, the non-Bragg resonances occur far from the edges of the Brillouin zone and open additional forbidden bands. The experimental observations confirm the existence of these resonances, and the measurements for the transmission properties showing both Bragg and non-Bragg band gaps agree fairly well with the theoretical predictions obtained by the plane-wave expansion method. It is shown that both Bragg and non-Bragg resonances highly depend on the symmetry of the corrugations on the opposite sidewall. As the relative shift between the two corrugations increases from zero to the half period of the corrugations, the Bragg gap shrinks and vanishes, but the non-Bragg gap varies in the opposite way, reaching its maximum, which is impressively wide and much more efficient in reflecting water waves.