Hydrazide-hydrazones as Small Molecule Tropomyosin Receptor Kina se A (TRKA) Inhibitors: Synthesis, Anticancer Activities, ADME and Molecular Docking Studies.

Aim: The aim of the study was to search for new anticancer agents as TRKA inhibitors.

Background: A series of new salicylic acid hydrazide hydrazones were synthesized and evaluated for their in vitro anticancer activities against lung (A549), ovarian (SK-OV-3), skin (SK-MEL-2), and colon (HCT15) cancer cell lines, and tropomyosin receptor kinase A (TRKA) inhibitory activities.

Objective: In this study, we focused on the synthesis and anticancer properties evaluation of salicylic acid hydrazide hydrazones as TRKA inhibitors.

Inhibitory effect of leaf extract on ultraviolet-induced photoaging-associated ion channels and enzymes.

In traditional Korean/Asian medicine, Salvia plebeia R.Br. () leaves are used to treat inflammatory diseases, including dermatitis, cough, asthma and toothache.

Physicochemical analyses of a bioactive 4-aminoantipyrine analogue - synthesis, crystal structure, solid state interactions, antibacterial, conformational and docking studies.

A novel Schiff base derivative of 4-aminoantipyrine, that is, ()-4-(2-methoxybenzylideneamino)-1,5-dimethyl-2-phenyl-1-pyrazol-3(2)-one (MBA-dMPP), was synthesized and characterized by FT-IR, H-NMR, and EI-MS. Single-crystal X-ray diffraction data revealed MBA-dMPP adopts a configuration around its central C=N double bond, and forms orthorhombic crystals. XRD revealed that MBA-dMPP possess two different planes, in which the pyrazolone and benzylidene groups attached to C9 of the pyrazolone ring are almost coplanar and the phenyl ring connected to the N1 atom of the pyrazolone moiety lies in another plane.

13-Ethylberberine reduces HMGB1 release through AMPK activation in LPS-activated RAW264.7 cells and protects endotoxemic mice from organ damage.

High mobility group box 1 (HMGB1), a highly conserved non-histone DNA-binding protein, plays an important role in the pathogenesis of sepsis. Previously, the authors reported 13-ethylberberine (13-EBR) has anti-inflammatory and antibacterial effects. However, the effect of 13-EBR on HMGB1 release was not investigated.

Synthesis, anticancer, and docking studies of salicyl-hydrazone analogues: A novel series of small potent tropomyosin receptor kinase A inhibitors.

A series of novel salicyl-hydrazone analogues were synthesized and evaluated for their in vitro cytotoxic activities in five human cancer cell lines, namely, lung cancer (A549), ovarian cancer (SK-OV-3), skin cancer (SK-MEL-2), colon cancer (HCT15) and pancreatic cancer (MIA-PaCa-2) cells, and for their in vitro tropomyosin receptor kinase A (TrkA) inhibitory activities. Each of the compounds showed significant cytotoxicity against all cancer cells. Compound 3i was found to be most potent against all cancer cell lines with IC values of 2.

Foeniculum vulgare extract and its constituent, trans-anethole, inhibit UV-induced melanogenesis via ORAI1 channel inhibition.

Background: Ultraviolet radiation exposure is the most important cause of extrinsic skin aging (photoaging), which causes skin wrinkling and hyperpigmentation. Although many factors are involved in the photoaging process, calcium release-activated calcium channel protein 1 (ORAI1) has been reported to be involved in UV-induced melanogenesis.

Objective: The aim of the present study was to find inhibitory effects of the extract of Foeniculum vulgare (fennel) fruits on ORAI1 ion channels and UV-induced melanogenesis in melanoma cells and to identify its active constituents.

13-Methylberberine reduces HMGB1 release in LPS-activated RAW264.7 cells and increases the survival of septic mice through AMPK/P38 MAPK activation.

High mobility group box 1 (HMGB1), a late phase cytokine of sepsis, is viewed as a potential target for the treatment of sepsis. The authors considered that 13-methylberberine (13-MB) might reduce circulating HMGB1 levels and increase survival in a mouse model of sepsis by activating AMP-activated protein kinase (AMPK). Western blot analysis and vascular contraction testing were performed using RAW264.

Inhibitory Effect of Valencene on the Development of Atopic Dermatitis-Like Skin Lesions in NC/Nga Mice.

Valencene (VAL) isolated from Cyperus rotundus possesses various biological effects such as antiallergic and antimelanogenesis activity. We investigated the effect of VAL on atopic dermatitis (AD) skin lesions and their molecular mechanisms. We topically applied VAL to 1-chloro-2,4-dinitrobenzene (DNCB) sensitized NC/Nga mice.

Biological and quantitative-SAR evaluations, and docking studies of (E)-N -benzylidenebenzohydrazide analogues as potential antibacterial agents.

A series of 15 (E)-N'-benzylidenebenzohydrazide analogues were evaluated for their antimicrobial activities against eleven pathogenic and food-borne microbes, namely, S. aureus (G(+)), L. monocytogenes (G(+)), B.

Skin protective effect of guava leaves against UV-induced melanogenesis via inhibition of ORAI1 channel and tyrosinase activity.

Ultraviolet (UV) irradiation is a major environmental factor affecting photoageing, which is characterized by skin wrinkle formation and hyperpigmentation. Although many factors are involved in the photoageing process, UV irradiation is thought to play a major role in melanogenesis. Tyrosinase is the key enzyme in melanin synthesis; therefore, many whitening agents target tyrosinase through various mechanisms, such as direct interference of tyrosinase catalytic activity or inhibition of tyrosinase mRNA expression.

Synthesis, spectroscopic and computational studies of 2-(thiophen-2-yl)-2,3-dihydro-1H-perimidine: An enzymes inhibition study.

The biologically relevant molecule; 2-(thiophen-2-yl)-2,3-dihydro-1H-perimidine was synthesized and characterized by FT-IR, UV, H and C NMR, MS, CHN microanalysis, X-ray crystallography as well as by theoretical, B3LYP/6-311++G(d,p), calculations. The vibrational bands appearing in the FT-IR were assigned with great accuracy using animated modes. Molecular properties like HOMO-LUMO analysis, chemical reactivity descriptors, MEP mapping, dipole moment and natural charges have been presented at the same level of theory.

Potent acetylcholinesterase inhibitors: Synthesis, biological assay and docking study of nitro acridone derivatives.

The reaction of o-halobenzoic acid with aniline derivatives and their subsequent cyclization reaction yielded the acridone derivatives. The series of nitro acridone derivatives were prepared by Ullmann condensation in presence of copper as catalyst and were characterized by FTIR, (1)H, (13)C NMR and mass spectra. The structure of 5-nitro-(2-phenyl amino) benzoic acid (4) was confirmed by X-ray crystallography and was found to crystallize in P21/c space group.

Synthesis, characterization, molecular docking and biological studies of self assembled transition metal dithiocarbamates of substituted pyrrole-2-carboxaldehyde.

A series of self assembled 3d transition metal dithiocarbamate, M(pdtc) [where M=Mn(II), Fe(II), Co(II), Ni(II) and Cu(II)] have been synthesized and spectroscopically characterized. The bidentate dithiocarbamate ligand Na2pdtc (Disodium-1,4-phenyldiaminobis (pyrrole-1-sulfino)dithioate) was prepared by insertion reaction of carbondisulfide with Schiff base, N,N'-bis-(1H-pyrrol-2-ylmethylene)-benzene-1,4-diamine (L1) in basic medium. The simple substitution reaction between the metal halide and Na2pdtc yielded the title complexes in moderate yields.

Valencene from the Rhizomes of Cyperus rotundus Inhibits Skin Photoaging-Related Ion Channels and UV-Induced Melanogenesis in B16F10 Melanoma Cells.

Ultraviolet (UV) radiation deeply penetrates skin and causes inflammation and pigmentary changes and triggers immune responses. Furthermore, accumulating evidence suggests that calcium ion channels, such as TRPV1 and ORAI1, mediate diverse dermatological processes including melanogenesis, skin wrinkling, and inflammation. The rhizomes of Cyperus rotundus have been used to treat inflammatory diseases including dermatitis.

Synthesis, biological evaluation, drug-likeness, and in silico screening of novel benzylidene-hydrazone analogues as small molecule anticancer agents.

A series of fifteen benzylidene-hydrazone analogues (3a-o), including eight new compounds, were synthesized and evaluated for their cytotoxic activities in four human cancer cell lines and for their antioxidant activities using DPPH. Of the tested compounds 3e, which possesses two methoxy substituents in its benzylidene phenyl ring, was found to be potently cytotoxic to all cancer cell lines tested with IC50 values of 0.12 (lung), 0.

β-Caryophyllene alleviates D-galactosamine and lipopolysaccharide-induced hepatic injury through suppression of the TLR4 and RAGE signaling pathways.

Agastache rugosa (A. rugosa, Labiatae), a perennial herb spread throughout Korean fields, is widely consumed as a wild edible vegetable and is used in folk medicine. This study examined the hepatoprotective mechanisms of β-caryophyllene (BCP), a major bicyclic sesquiterpene of A.

Effects of Lupenone, Lupeol, and Taraxerol Derived from Adenophora triphylla on the Gene Expression and Production of Airway MUC5AC Mucin.

Background: Adenophora triphylla var. japonica is empirically used for controlling airway inflammatory diseases in folk medicine. We evaluated the gene expression and production of mucin from airway epithelial cells in response to lupenone, lupeol and taraxerol derived from Adenophora triphylla var.

Anti-inflammatory and antioxidant effects of coumarins isolated from Foeniculum vulgare in lipopolysaccharide-stimulated macrophages and 12-O-tetradecanoylphorbol-13-acetate-stimulated mice.

Context: Foeniculum vulgare (F. vulgare) is traditionally used to treat inflammatory diseases. Recently, anti-inflammatory and antioxidant activities of methanol extract of the fruits of F.

Syntheses, crystal structure, Hirshfeld surfaces, fluorescence properties, and DFT analysis of benzoic acid hydrazone Schiff bases.

Two hydrazone Schiff base analogues, namely, (E)-N'-(4-hydroxy-3-methoxybenzylidene)benzohydrazide (3a) and (E)-N'-(4-methoxybenzylidene)benzohydrazide (3b), were synthesized using a mild, efficient method and characterized by (1)H NMR, mass spectrometry, elemental analysis, and single-crystal X-ray diffraction. X-ray analysis of a single crystal of 3a revealed a tetragonal, space group I4(1)/a structure, with an E-configuration around the azomethine (C8N2) double bond. In this structure, the NH and OH groups act as proton donors and the >CO and N groups as proton acceptors, and these facilitate hydrogen bond formation in the crystal state.

Eco-friendly synthesis, physicochemical studies, biological assay and molecular docking of steroidal oxime-ethers.

The aim of this study was to report the synthesis of biologically active compounds; 7-(2'-aminoethoxyimino)-cholest-5-ene (4), a steroidal oxime-ether and its derivatives (5, 6) via a facile microwave assisted solvent free reaction methodology. This new synthetic, eco-friendly, sustainable protocol resulted in a remarkable improvement in the synthetic efficiency (85-93 % yield) and high purity using basic alumina. The synthesized compounds were screened for their antibacterial against six bacterial strains by disc diffusion method and antioxidant potential by DPPH assay.

Synthesis, antibacterial, antioxidant activity and QSAR studies of novel 2-arylidenehydrazinyl-4-arylthiazole analogues.

A novel series of 2-arylidenehydrazinyl-4-arylthiazole analogues (3a-p) was designed and synthesized in excellent yields using a rapid, simple, efficient methodology. Sixteen novel compounds were screened for in vitro antimicrobial activities against eleven bacteria, namely, Staphylococcus aureus, Listeria monocytogenes, Enterococcus faecalis, Bacillus subtilis, Klebsiella pneumonia, Citrobacter freundii, Cronobacter sakazakii, Salmonella enteritidis, Escherichia coli, Yersinia pestis, and Pseudomonas aeruginosa. All 16 compounds showed significant anti-bacterial activities against both Gram-positive and Gram-negative bacteria.

Inhibitory effect of oleanolic acid from the rhizomes of Cyperus rotundus on transient receptor potential vanilloid 1 channel.

Cyperus rotundus is used as an analgesic and sedative in oriental medicine and has been reported to exhibit antinociceptive and anti-inflammatory effects. On the other hand, the transient receptor potential vanilloid 1 channel is a nonselective cation channel that senses various noxious chemical and thermal stimuli. However, it has recently been reported that the epidermally expressed transient receptor potential vanilloid 1 channel is involved in heat- and UV-induced skin aging.

Protective mechanisms of acacetin against D-galactosamine and lipopolysaccharide-induced fulminant hepatic failure in mice.

This study examined the hepatoprotective effects of acacetin (1), a flavonoid isolated from Agastache rugosa, against d-galactosamine (GalN) and lipopolysaccharide (LPS)-induced fulminant hepatic failure. Mice were given an intraperitoneal injection of 1 (25, 50, and 100 mg/kg), or the vehicle alone (5% dimethyl sulfoxide-saline), 1 h before GalN (800 mg/kg)/LPS (40 μg/kg) treatment and sacrificed at 6 h after GalN/LPS injection. GalN/LPS markedly increased mortality and serum aminotransferase activity, and these increases were attenuated by 1.

Protective effects of lupeol against D-galactosamine and lipopolysaccharide-induced fulminant hepatic failure in mice.

This study examined the hepatoprotective effects of lupeol (1, a major active triterpenoid isolated from Adenophora triphylla var. japonica) against d-galactosamine (GalN) and lipopolysaccharide (LPS)-induced fulminant hepatic failure. Mice were orally administered 1 (25, 50, and 100 mg/kg; dissolved in olive oil) 1 h before GalN (800 mg/kg)/LPS (40 μg/kg) treatment.

Dehydrocostuslactone inhibits LPS-induced inflammation by p38MAPK-dependent induction of hemeoxygenase-1 in vitro and improves survival of mice in CLP-induced sepsis in vivo.

We investigated the hypothesis that the administration of dehydrocostuslactone (DL), a sesquiterpene lactone found in Saussurea lappa Clarke (Compositae), might reduce organ failure and increase survival in a cecal ligation and puncture (CLP)-induced mouse model of sepsis due to HO-1 induction. Treatment of RAW264.7 cells with DL increased HO-1 expression in a time- and concentration-dependent manner, and this up-regulation of HO-1 by DL was significantly inhibited by silencing either Nrf2 and p38 or treating cells with SB203580 (a p38MAPK inhibitor), but it was not inhibited in the presence of SP600125 (an ERK inhibitor), PD98059 (a JNK inhibitor), or LY294002 (PI3K inhibitor).