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We investigated a panel of 14 compounds belonging to the monothiocarbamate (MTC) and dithiocarbamate (DTC) series against the β-carbonic anhydrase 3 (β-CA3) of Mycobacterium tuberculosis (Mtb). We also evaluated all compounds for toxicity using 1–5-day post fertilisation zebrafish embryos. 11 out of the 14 investigated derivatives showed effective nanomolar or submicromolar in vitro inhibition against the β-CA3 (KIs 2.4–812.0 nM), and among them four DTCs of the series (8–10 and 12) showed very significant inhibition potencies with KIs between 2.4 and 43 nM. Out of 14 compounds screened for toxicity and safety 9 compounds showed no adverse phenotypic effects on the developing zebrafish larvae at five days of exposure. The results of in vitro inhibition and the toxicological evaluation of our study suggest that 5 compounds are suitable for further in vivo preclinical characterisation in zebrafish model.

Background The frequent usage of broad-spectrum insecticides like cypermethrin in agriculture activities could lead to the development of resistance in insects like Amsacta albistriga. Objectives The present study was conducted to understand the toxicity of cypermethrin with and without a combination of three enzyme inhibitors (PBO, DEM, and TPP) on A. albistriga using a topical bioassay. Methodology The in vitro and in vivo studies were conducted to understand the effect of three enzyme inhibitors such as piperonyl butoxide (PBO) and diethyl maleate (DEM) and triphenyl phosphate along with six different concentration of cypermethrin on the activities of acetylcholinesterase (AChE), esterase (EST), glutathione S-transferase (GST), and mixed-function oxidase (MFO) of A. albistriga. Results Bioassay shows elevated LC50 for cypermethrin (63.32 ppm) whereas in a combination of PBO cypermethrin LC50 values were reduced into 12.039 ppm followed by TPP combination as 13.234 ppm. In vitro and in vivo inhibition analysis shows AChE inhibition by PBO P < 0.01, esterase inhibition by PBO, and TPP were less; GST inhibition by DEM was observed at P < 0.001. Native PAGE results revealed that the in vitro AChE isoenzyme inhibition could be possible by PBO synergism with cypermethrin in A. albistriga. Conclusions The overall results conclude that the PBO and TPP enzyme inhibitors could be fine synergist molecules when it mixed with cypermethrin insecticide to control and manage the insecticide-resistant Amsacta albistriga in the field.

Summary Soy protein isolates (SPI) films were evaluated as carriers of citral and limonene, and their physical and antifungal properties were evaluated. The presence of antimicrobials in SPI films resulted in changes on colour without affecting the transparency. Films with citral added were more extensible; however, a reduction in tensile strength and elastic modulus was observed in films with limonene added. Aroma compounds addition in films induced a slight increase in water vapour properties in relation to discontinuity of network proteins evidenced by SEM. Besides, FTIR spectra evidenced a partial alteration of SPI secondary structure. Citral was less retained than limonene. The increase in limonene release with high relative humidity was explained by increase in protein chain mobility. SPI films enriched with limonene exhibited strong antifungal activity against the postharvest decay pathogen Penicillium italicum under storage conditions.

The inhibition activities and mechanisms of four anthocyanins including cyanidin-3-glucoside, cyanidin-3,5-glucoside, cyanidin-3-rutinoside, and peonidin-3-glucoside, against porcine pancreatic α-amylase were investigated through in vitro and in silico studies. The in vitro inhibition study demonstrated that the four anthocyanins competitively inhibited porcine pancreatic α-amylase, which was later verified by the in silico molecular docking study that showed all the anthocyanins bound exclusively to the active site of porcine pancreatic α-amylase. Cyanidin-3-glucoside was found to have the highest inhibition activity with the K i value of 0.014 mM, followed by cyanidin-3-rutinoside, cyanidin-3,5-glucoside, and peonidin-3-glucoside with the K i value of 0.019, 0.020, and 0.045 mM, respectively. Results obtained from the in silico study also showed that the four anthocyanins were surrounded by the side chains of the active site of porcine pancreatic α-amylase, among which the side chain of GLU233 was supposed to play a key role in imparting the inhibition activity of anthocyanins.

Gençer, Nahit (Balikesir Author), Human serum paraoxonase 1 (PON1; EC 3.1.8.1) is a high-density lipoprotein associated, calcium-dependent enzyme that hydrolyses aromatic esters, organophosphates and lactones and can protect the low-density lipoprotein against oxidation. In this study, in vitro effect of some hydroxy and dihydroxy ionic coumarin derivatives (1-20) on purified PON1 activity was investigated. Among these compounds, derivatives 11-20 are water soluble. In investigated compounds, compounds 6 and 13 were found the most active (IC50 = 35 and 34 mu M) for PON1, respectively. The present study has demonstrated that PON1 activity is very highly sensitive to studied coumarin derivatives., Balikesir University Research project 2014/54

Statine-based inhibitors of Plasmepsin II (PLMII) coupled with Primaquine have been designed using the `double-drug' approach. The IC50 values for PLMII inhibition ranged from 0.59 to 400 nM and the best IC50 value for inhibition of Plasmodium falciparum growth in vitro was 0.4 μM, which represent a remarkable improvement compared to other statine-based PLMII inhibitors.

Protein phosphatase 5 (PP5) is a unique member of serine/threonine phosphatases which has been recognized in regulation of diverse cellular processes. A cDNA fragment encoding PP5 (EcPP5) was cloned and characterized from the cantharidin-producing blister beetle, E. chinensis. EcPP5 contains an open reading frame of 1500 bp that encodes a protein of 56.89 kDa. The deduced amino acid sequence shares 88% and 68% identities to the PP5 of Tribolium castaneum and humans, respectively. Analysis of the primary sequence shows that EcPP5 has three TPR (tetratricopeptide repeat) motifs at its N-terminal region and contains a highly conserved C-terminal catalytic domain. RT-PCR reveals that EcPP5 is expressed in all developmental stages and in different tissues. The recombinant EcPP5 (rEcPP5) was produced in Escherichia coli and purified to homogeneity. The purified protein exhibited phosphatase activity towards pNPP (p-nitrophenyl phosphate) and phosphopeptides, and its activity can be enhanced by arachidonic acid. In vitro inhibition study revealed that protein phosphatase inhibitors, okadaic acid, cantharidin, norcantharidin and endothall, inhibited its activity. Further, protein phosphatase activity of total soluble protein extract from E. chinensis adults could be impeded by these inhibitors suggesting there might be some mechanism to protect this beetle from being damaged by its self-produced cantharidin.

WOS: 000311310400015, PubMed: 22971832, Human serum paraoxonase 1 (PON1; EC 3.1.8.1) is a high-density lipoprotein associated, calcium-dependent enzyme that hydrolyses aromatic esters, organophosphates and lactones and can protect the low-density lipoprotein against oxidation. In this study, in vitro inhibition effect of some dihydroxy coumarin compounds namely 6,7-dihydroxy-3-(2-methylphenyl)-2H-chromen-2-one (A), 6,7-dihydroxy-3-(3-methylphenyl)-2H-chromen-2-one (B) and 6,7-dihydroxy-3-(4-methylphenyl)-2H-chromen-2-one (C) on purified PON1 were investigated by using paraoxon as a substrate. PON1 was purified using two-step procedures, namely ammonium sulphate precipitation and Sepharose-4B-l-tyrosine-1-naphthylamine hydrophobic interaction chromatography. The purified enzyme had a specific activity of 11.76 U/mg. The dihydroxy coumarin derivatives of A and B compounds inhibited PON1 enzyme activity in a noncompetitive inhibition manner with K (i) of 0.0080 +/- 0.256 and 0.0003 +/- 0.018 mM values, respectively. C compound exerted an uncompetitive inhibition of PON1 enzyme activity with K (i) of 0.0010 +/- 0.173 mM. Moreover, dihydroxy coumarin derivatives of A, B and C compounds were effective inhibitors on purified human serum PON1 activity with IC50 of 0.012, 0.022 and 0.003 mM values, respectively. IC50 value of unsubstituted 6,7 dihydroxy coumarin was found as 0.178 mM. The present study has demonstrated that PON1 activity is very highly sensitive to studied coumarin derivatives.

Non-carboxylic acid containing bioisosteres of (5-arylidene-2,4-dioxothiazolidin-3-yl)acetic acids, which are active as aldose reductase (ALR2) inhibitors, were designed by replacing the carboxylic group with the trifluoromethyl ketone moiety. The in vitro evaluation of the ALR2 inhibitory effects of these trifluoromethyl substituted derivatives led to the identification of two inhibitors effective at low micromolar doses. It was further confirmed that a carboxylic chain on N-3 of the thiazolidinedione scaffold is a determining requisite to obtain the highest efficacy levels; however, it is not essential for the interaction with the target enzyme and it can be replaced by different polar groups, thus obtaining less ionised or unionised inhibitors.