Green surfactants for corrosion control: Design, performance and applications.

Surfactants enjoy an augmented share of hydrophilicity and hydrophobicity and are well-known for their anticorrosive potential. The use of non-toxic surfactants is gaining growing interest because of the scaling demands of green chemistry. Green surfactants have successfully replaced traditional toxic surfactant-based corrosion inhibitors. Recently, many reports described the corrosion inhibition potential of green surfactants. The present article aims to describe the recent advancements in using green surfactants in corrosion mitigation. They create a charge transfer barrier through their adsorption at the interface of the metal and the environment. Their adsorption is well explained by the Langmuir adsorption isotherm. In the adsorbed layer, their hydrophilic polar heads orient toward the metal side and their hydrophobic tails orient toward the solution side. They block the active sites and retard the anodic and cathodic and act as mixed-type inhibitors. Their adsorption and bonding nature are fruitfully supported by surface analyses. They can form mono- or multilayers depending upon the nature of the metal, electrolyte and experimental conditions. The challenges and opportunities of using green surfactants as corrosion inhibitors have also been described.

Hybridization-based design of novel anticholinesterase indanone-carbamates for Alzheimer's disease: Synthesis, biological evaluation, and docking studies.

Inspired by the structures of donepezil and rivastigmine, a novel series of indanone-carbamate hybrids was synthesized using the pharmacophore hybridization-based design strategy, and their biological activities toward acetylcholinesterase (AChE) and butyrylcholinesterase were evaluated. Among the synthesized compounds, 4d and 4b showed the highest AChE inhibitory activities with IC50 values in the micromolar range (compound 4d: IC50 = 3.04 µM; compound 4b: IC50 = 4.64 µM). Moreover, the results of the Aß1-40 aggregation assay revealed that compound 4b is a potent Aß1-40 aggregation inhibitor. The kinetics of AChE enzymatic activity in the presence of 4b was investigated, and the results were indicative of a reversible partial noncompetitive type of inhibition. A molecular docking study was conducted to determine the possible allosteric binding mode of 4b with the enzyme. The allosteric nature of AChE inhibition by these compounds provides the opportunity for the design of subtype-selective enzyme inhibitors. The presented indanone-carbamate scaffold can be structurally modified and optimized through medicinal chemistry-based approaches for designing novel multitargeted anti-Alzheimer agents.

Glutinous rice (Oryza sativa L.) protein extract with potent α-amylase inhibitory activity.

This research screened for α-amylase inhibitory activity of twenties-five varieties Thai indigenous rice seeds. Based on specific inhibition, crude protein of var. Gai Ngaw (Gs. No. 13719) was selected for purification. The unbound proteins of the Q-Sepharose column named partially purified rice α-amylase inhibitor (RAI) revealed MW of approximately 14.4 kDa. The RAI was stable at pH 4 to 7 and heat stable up to 80 °C. The RAI had IC50 of 15.92 ± 1.08 µg/ml. The double reciprocal plot implied a mixed-type inhibitor. The Dixon and Cornish-Bowden plots were used to estimate Ki and αKi. This suggested Thai indigenous rice seeds could potentially be developed as a food supplement for blood sugar and weight controls.

Chemoproteomic Profiling of a Pharmacophore-Focused Chemical Library.

Pharmacophore-focused chemical libraries are continuously being created in drug discovery programs, yet screening assays to maximize the usage of such libraries are not fully explored. Here, we report a chemical proteomics approach to reutilizing a focused chemical library of 1,800 indole-containing molecules for discovering uncharacterized ligand-protein pairs. Gel-based protein profiling of the library using a photo-affinity indole probe 1 enabled us to find new ligands for glyoxalase 1 (Glo1), an enzyme involved in the detoxification of methylglyoxal. Structure optimization of the ligands yielded an inhibitor for Glo1 (9). Molecule 9 increased the cellular methylglyoxal levels in human cells and suppressed the osteoclast formation of mouse bone marrow-derived macrophages. X-ray structure analyses revealed that the molecule lies at a site abutting the substrate binding site, which is consistent with the enzyme kinetic profile of 9. Overall, this study exemplifies how chemical proteomics can be used to exploit existing focused chemical libraries.

Allosteric feedback inhibition of pyridoxine 5'-phosphate oxidase from Escherichia coli.

In Escherichia coli, the synthesis of pyridoxal 5'-phosphate (PLP), the catalytically active form of vitamin B6, takes place through the so-called deoxyxylulose 5-phosphate-dependent pathway, whose last step is pyridoxine 5'-phosphate (PNP) oxidation to PLP, catalyzed by the FMN-dependent enzyme PNP oxidase (PNPOx). This enzyme plays a pivotal role in controlling intracellular homeostasis and bioavailability of PLP. PNPOx has been proposed to undergo product inhibition resulting from PLP binding at the active site. PLP has also been reported to bind tightly at a secondary site, apparently without causing PNPOx inhibition. The possible location of this secondary site has been indicated by crystallographic studies as two symmetric surface pockets present on the PNPOx homodimer, but this site has never been verified by other experimental means. Here, we demonstrate, through kinetic measurements, that PLP inhibition is actually of a mixed-type nature and results from binding of this vitamer at an allosteric site. This interpretation was confirmed by the characterization of a mutated PNPOx form, in which substrate binding at the active site is heavily hampered but PLP binding is preserved. Structural and functional connections between the active site and the allosteric site were indicated by equilibrium binding experiments, which revealed different PLP-binding stoichiometries with WT and mutant PNPOx forms. These observations open up new horizons on the mechanisms that regulate E. coli PNPOx, which may have commonalities with the mechanisms regulating human PNPOx, whose crucial role in vitamin B6 metabolism and epilepsy is well-known.

The inhibitory effect of farnesiferol C against catalase; Kinetics, interaction mechanism and molecular docking simulation.

Farnesiferol C (FC) is a natural sesquiterpene coumarin, which includes a widely range of biological activities. In this work, effects of FC on the structure and catalytic function of bovine liver catalase (BLC) was assessed by various spectroscopic and theoretical methods. Kinetic studies showed that FC has a remarkable inhibitory activity on BLC via mixed-type inhibition. The IC50 value as the inhibitory strength of FC was evaluated 1.5µM. Fluorescence spectroscopy, synchronous fluorescence, CD spectroscopy and UV-vis absorption studies revealed conformational changes in the tertiary and secondary structure of BLC as well as the position of the heme group in the presence of different concentrations of FC. Fluorescence studies revealed that FC quenches intrinsic emission of catalase via static quenching process. The binding constants at 298 and 310K were calculated 1.17×105M-1 and 1.0×105M-1, respectively. Thermodynamic data suggested that hydrophobic interactions play a major role in the binding reaction of FC on BLC. Structural studies indicated that the binding FC to the enzyme is responsible for the changes of the percentage of secondary structures' elements especially α-helix. From the simulation data, the role of Arg353 residue in the mechanism of catalase inhibition has been recognized.

Chemical constituents from Taraxacum officinale and their α-glucosidase inhibitory activities.

Three novel butyrolactones (1-3) and butanoates (4-6), namely taraxiroside A-F, were isolated from Taraxacum officinale along with twenty-two known compounds (7-28). Their chemical structures were elucidated by interpretation of spectroscopic data and comparison with those of literatures. All isolates were evaluated for their α-glucosidase inhibitory activities. Novel compounds 1-6 (IC50 145.3-181.3 µM) showed inhibitory activities similar to that of acarbose (IC50 179.9 µM). Compound 7 and 12 were the most potent inhibitor with IC50 values of 61.2 and 39.8 µM respectively. Compounds 2 and 12 showed as mixed-type inhibition, whereas compound 7 and acarbose showed competitive inhibition.

Identification of a trichothecene production inhibitor by chemical array and library screening using trichodiene synthase as a target protein.

Trichothecene mycotoxins often accumulate in apparently normal grains of cereal crops. In an effort to develop an agricultural chemical to reduce trichothecene contamination, we screened trichothecene production inhibitors from the compounds on the chemical arrays. By using the trichodiene (TDN) synthase tagged with hexahistidine (rTRI5) as a target protein, 32 hit compounds were obtained from chemical library of the RIKEN Natural Product Depository (NPDepo) by chemical array screening. At 10µgmL-1, none of the 32 chemicals inhibited trichothecene production by Fusarium graminearum in liquid culture. Against the purified rTRI5 enzyme, however, NPD10133 [progesterone 3-(O-carboxymethyl)oxime amide-bonded to phenylalanine] showed weak inhibitory activity at 10µgmL-1 (18.7µM). For the screening of chemicals inhibiting trichothecene accumulation in liquid culture, 20 analogs of NPD10133 selected from the NPDepo chemical library were assayed. At 10µM, only NPD352 [testosterone 3-(O-carboxymethyl)oxime amide-bonded to phenylalanine methyl ester] inhibited rTRI5 activity and trichothecene production. Kinetic analysis suggested that the enzyme inhibition was of a mixed-type. The identification of NPD352 as a TDN synthase inhibitor lays the foundation for the development of a more potent inhibitor via systematic introduction of wide structural diversity on the gonane skeleton and amino acid residues.

Mobola plum seed methanolic extracts exhibit mixed type inhibition of angiotensin -converting enzyme in vitro

Objective To explore the possible inhibitory potentials and mechanism by Mobola plum (Parinari curatellifolia) seeds crude methanol (CE) and flavonoid-rich (FE) extracts on angiotensin-1-converting enzyme (ACE ). Methods The sensitivity and kinetic model of inhibition of CE and FE on ACE using N-[3-(2-furyl)-acryloyl]-Phe-Gly-Gly as enzyme substrate for ACE was evaluated by Michealis Menten approach. The inhibition mechanism was explored from Lineweaver–Burk model and IC

Mobola plum seed methanolic extracts exhibit mixed type inhibition of angiotensin Ⅰ-converting enzyme in vitro

Objective:To explore the possible inhibitory potentials and mechanism by Mobola plum (Parinari curatellifolia) seeds crude methanol (CE) and flavonoid-rich (FE) extracts on angiotensin-1-converting enzyme (ACE I).Methods:The sensitivity and kinetic model of inhibition of CE and FE on ACE I using N-[3-(2-furyl)-acryloyl]-Phe-Gly-Gly as enzyme substrate for ACE I was evaluated by Michealis Menten approach.The inhibition mechanism was explored from LineweaverBurk model and IC50 was determined from Cheng-Prusoff empirical analysis.Results:The IC50 of CE and FE were 13.54 and 39.38 μg/mL,respectively.Both extracts exhibited mixed type inhibition with the inhibitory constant (Ki) of CE was between 0.38 and 0.37 μg/mL while that of FE showed a two-fold increase (1.62 μg/mL and 0.28 μg/mL).FE on ACE I demonstrated positive cooperativity with a Hill's coefficient of 1.89.Conclusions:The study reveals the superior ACE I inhibitory potential of CE over FE and suggest that mixed inhibition pattern of the enzyme might be the underlying mechanism of antihypertensive activity.

Multiple drugs compete for transport via the Plasmodium falciparum chloroquine resistance transporter at distinct but interdependent sites.

Mutations in the "chloroquine resistance transporter" (PfCRT) are a major determinant of drug resistance in the malaria parasite Plasmodium falciparum. We have previously shown that mutant PfCRT transports the antimalarial drug chloroquine away from its target, whereas the wild-type form of PfCRT does not. However, little is understood about the transport of other drugs via PfCRT or the mechanism by which PfCRT recognizes different substrates. Here we show that mutant PfCRT also transports quinine, quinidine, and verapamil, indicating that the protein behaves as a multidrug resistance carrier. Detailed kinetic analyses revealed that chloroquine and quinine compete for transport via PfCRT in a manner that is consistent with mixed-type inhibition. Moreover, our analyses suggest that PfCRT accepts chloroquine and quinine at distinct but antagonistically interacting sites. We also found verapamil to be a partial mixed-type inhibitor of chloroquine transport via PfCRT, further supporting the idea that PfCRT possesses multiple substrate-binding sites. Our findings provide new mechanistic insights into the workings of PfCRT, which could be exploited to design potent inhibitors of this key mediator of drug resistance.

Discovery of mixed type thymidine phosphorylase inhibitors endowed with antiangiogenic properties: synthesis, pharmacological evaluation and molecular docking study of 2-thioxo-pyrazolo[1,5-a][1,3,5]triazin-4-ones. Part II.

In our drug discovery program, a series of 2-thioxo-pyrazolo[1,5-a][1,3,5]triazin-4-ones were designed, synthesized and evaluated for their TP inhibitory potential. All the synthesized analogues conferred a varying degree of TP inhibitory activity, comparable or better than positive control, 7-deazaxanthine (7-DX, 2) (IC50 value = 42.63 µM). A systematic approach to the lead optimization identified compounds 3c and 4a as the most promising TP inhibitors, exhibiting mixed mode of enzyme inhibition. Moreover, selected compounds demonstrated the ability to attenuate the expression of the angiogenic markers (viz. MMP-9 and VEGF) in MDA-MB-231 cells at sublethal concentrations. In addition, molecular docking studies revealed the plausible binding orientation of these inhibitors towards TP, which was in accordance with the experimental results. Taken as a whole, these compounds would constitute a new direction for the design of novel TP inhibitors with promising antiangiogenic properties.

Synthesis and evaluation of 2-(1H-indol-3-yl)-4-phenylquinolines as inhibitors of cholesterol esterase.

A series of 2-(substituted) phenyl and 2-indolyl quinoline derivatives (10a-l) was synthesized by an efficient microwave-assisted, trifluoroacetic acid-catalyzed, solvent-free method. Evaluation of the inhibitory activity led to the identification of two quinoline inhibitors of cholesterol esterase. 2-(1H-Indol-3-yl)-6-nitro-4-phenylquinoline (10l; IC50=1.98µM) was characterized as a mixed-type inhibitor with a pronounced competitive binding mode.

A structure-activity relationship study of 1,2,4-triazolo[1,5-a][1,3,5]triazin-5,7-dione and its 5-thioxo analogues on anti-thymidine phosphorylase and associated anti-angiogenic activities.

Thirty-three 1,2,4-triazolo[1,5-a][1,3,5]triazin-5,7-dione and its 5-thioxo analogues were designed and synthesized which contained different substituents at meta- and/or para-positions of 2-phenyl or 2-benzyl ring attached to the fused ring structure. The preliminary pharmacological evaluation demonstrated that the 5-thioxo analogues of 1,2,4-triazolo[1,5-a][1,3,5]triazine exhibited a varying degree of inhibitory activity towards thymidine phosphorylase, comparable or better than reference compound, 7-Deazaxanthine (7-DX, 2) (IC50 value = 42.63 µM). Moreover, compounds 5q and 6i displayed a mixed-type of inhibitory mechanism in the presence of variable concentrations of thymidine (dThd). In addition, selected compounds were found to have a noticeable inhibitory effect on the expression of angiogenesis markers, including VEGF and MMP-9 in MDA-MB-231 breast cancer cells.

Synthesis and in vitro evaluation of 1,2,4-triazolo[1,5-a][1,3,5]triazine derivatives as thymidine phosphorylase inhibitors.

In our lead finding program, a series of 1,2,4-triazolo[1,5-a][1,3,5]triazine derivatives were synthesized, and their in vitro thymidine phosphorylase inhibitory potential was explored. Among the different derivatives, compounds having keto group (C = O) at C7 and thioketo group (C = S) at C5 positions showed varying degrees of TP inhibitory activity comparable with positive control, 7-deazaxanthine (7-DX, 2) (IC50 value = 42.63 µm). Enzyme inhibition kinetics study suggested that compound IVn behaved as a mixed-type inhibitor of the enzyme with respect to thymidine (dThd) as a variable substrate. Compound IVn was also found to inhibit PMA-induced MMP-9 expression in MDA-MB-231 cells at sublethal concentrations. Computational docking study was performed to illustrate the enzyme inhibition kinetics and to explore the ligand-enzyme interactions.

Chemical composition and tyrosinase inhibitory activity of Cinnamomum cassia essential oil.

BACKGROUND: Essential oils extracted from aromatic plants exhibit important biological activities and have become increasingly important for scientific research. The essential oil extracted from Cinnamomum cassia Presl (CC-EO) has various functional properties, however, little information is available regarding the tyrosinase inhibitory activity. Therefore, the objectives of this study were to investigate the chemical composition and tyrosinase inhibitory activity of the CC-EO. RESULTS: cis-2-methoxycinnamic acid (43.06%) and cinnamaldehyde (42.37%) were found to be the two major components of the CC-EO identified by gas chromatography-mass spectrometry (GC-MS). The inhibitory activities of CC-EO and its major constituents were further evaluated against mushroom tyrosinase. The results showed that CC-EO and cinnamaldehyde exhibited anti-tyrosinase activities with IC50 values of 6.16 ± 0.04 mg/mL and 4.04 ± 0.08 mg/mL, respectively. However, cis-2-methoxycinnamic acid did not show any anti-tyrosinase activity. The inhibition kinetics were analyzed by Lineweaver-Burk plots and second replots, which revealed that CC-EO and cinnamaldehyde were mixed-type inhibitors. The inhibition constants (Ki) for CC-EO and cinnamaldehyde were calculated to be 4.71 ± 0.09 mg/mL and 2.38 ± 0.09 mg/mL, respectively. CONCLUSION: These results demonstrate that CC-EO and its major component, cinnamaldehyde, possess potent anti-tyrosinase activities and may be a good source for skin-whitening agents.