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Graphical abstract Highlights • Drug repositioning approach was used to predict the possible therapeutic effects of FDA approved drugs against AD disease. • The screened drugs showed good binding interaction profiles within active region of AChE. • Pharmacogenomics analysis depicted the possible associations between screened drugs and Alzheimer's genes. • Cinitapride showed a comparable results with standard and can be used as possible therapeutic agent in the treatment of AD. Abstract Novel drug development is onerous, time consuming and overpriced process with particularly low success and relatively high enfeebling rates. To overcome this burden, drug repositioning approach is being used to predict the possible therapeutic effects of FDA approved drugs in different diseases. Herein, we designed a computational and enzyme inhibitory mechanistic approach to fetch the promising drugs from the pool of FDA approved drugs against AD. The binding interaction patterns and conformations of screened drugs within active region of AChE were confirmed through molecular docking profiles. The possible associations of selected drugs with AD genes were predicted by pharmacogenomics analysis and confirmed through data mining. The stability behaviour of docked complexes (Drugs-AChE) were checked by MD simulations. The possible therapeutic potential of repositioned drugs against AChE were checked by in vitro analysis. Taken together, Cinitapride displayed a comparable results with standard and can be used as possible therapeutic agent in the treatment of AD. [ABSTRACT FROM AUTHOR]

[Display omitted] • A series of 1,3,4-thiadiazol-1,3,4-oxadiazol-acetamide derivatives (7a – 7j) were synthesized as elastase inhibitors. • The in-vitro elastase inhibitory activity of all synthesized compounds was determined successfully. • The kinetic mechanism was investigated by Lineweaver-Burk plots. • MTT assay was used to evaluate the cytotoxicity of all compounds on B16F10 melanoma cell lines. • Molecular docking was applied to investigate the binding affinity of compounds with elastase and the ligands showed good binding energy values. Considering the biological significance of 1,3,4-thiadiazole/oxadiazole heterocyclic scaffolds, a novel series of 1,3,4-thiadiazole-1,3,4-oxadiazole-acetamide derivatives (7a – j) was designed and synthesized using molecular hybridization. The inhibitory effects of the target compounds on elastase were evaluated, and all of these molecules were found to be potent inhibitors compared to the standard reference oleanolic acid. Compound 7f exhibited the excellent inhibitory activity (IC 50 = 0.06 ± 0.02 μM), which is 214-fold more active than oleanolic acid (IC 50 = 12.84 ± 0.45 μM). Kinetic analysis was also performed on the most potent compound (7f) to determine the mode of binding with the target enzyme, and it was discovered that 7f inhibits the enzyme in a competitive manner. Furthermore, the MTT assay method was used to assess their toxicity on the viability of B16F10 melanoma cell lines, and all compounds did not display any toxic effect on the cells even at high concentrations. The molecular docking studies of all compounds also justified with their good docking score and among them, compound 7f had a good conformational state with hydrogen bond interactions within the receptor binding pocket, which is consistent with the experimental inhibition studies. [ABSTRACT FROM AUTHOR]

Fusarium rot of muskmelon, caused by Fusarium spp., is one of the most important postharvest decays, that not only causes economic losses but leads to trichothecenes contamination. A rapid and sensitive method was developed for neosolaniol (NEO) analysis in muskmelon inoculated with F. sulphureum, utilizing acetonitrile/water (84:16, v/v) extraction and PriboFast M270 columns purification and UPLC-MS/MS detection. Method validation was evaluated by linearity (R ≥ 0.9990), recovery (88.1–136.9%), precision (RSD ≤ 3.97%) and sensitivity (LOD, 0.5 μg/kg; LOQ, 1.5 μg/kg). The effect of ozone treatment on Fusarium rot development and NEO accumulation in inoculated muskmelon was also evaluated. The results showed that UPLC-MS/MS method was suitable for analyzing NEO in inoculated muskmelon, and 1.10 mg/l ozone treatment for 120 min significantly controlled Fusarium rot development and NEO accumulation in fruits after 5, 8 and 11 days. In vivo tests showed that ozone at 1.10 mg/l effectively degraded NEO in acetonitrile. [ABSTRACT FROM AUTHOR]

[Display omitted] Herein, we have synthesized quinoline united various Schiff base derivatives (Q1-Q13) and systematically characterized them using diverse analytical practices such as 1H NMR, 13C NMR, FT-IR and LC-MS respectively. All of the target compounds that have been synthesized were tested for elastase inhibition, and the findings were compared to the standard drug oleanolic acid. Among the entire series, compound Q11 (IC 50 = 0.897 ± 0.015 µM) exhibit most promising elastase inhibitory activity than oleanolic acid (Standard) having an IC 50 value of 13.426 ± 0.015 µM. Also, the utmost effective compound Q11 was used for kinetic mechanism investigation based on in-vitro data, from which it has been concluded that compound Q11 inhibits elastase competitively. Furthermore, utilizing the MTT test approach, the most effective compounds were assessed for cytotoxicity on B16F10 melanoma cells. From the cytotoxicity experiment, the most potent compound did not display any hazardous response against B16F10 melanoma cells despite being treated at high concentrations. Additionally, the molecular docking study was settled to govern the binding interaction pattern among an enzyme and inhibitors. [ABSTRACT FROM AUTHOR]

• T-2 toxin produced by Fusarium spp., induced resistance against postharvest diseases on potato tubers. • Dry rot development of tubers was significantly reduced by T-2 toxin application. • The mechanism of induced resistance includes the activation of ROS and phenylpropanoid metabolism in potato tubers tissue. Potato (Solanum tubersosum L) is the most important non-grain source of human diet for the people living at poverty line. Potato suffers from many notorious biotic stresses, including dry rot caused by Fusarium spp. Treatments of potato tubers with 1 mg L−1 of T-2 toxin produced by Fusarium spp. induced resistance against Fusarium sulphureum by new elicitor-like activity. To investigate the mechanism of induced resistance by T-2 toxin against dry rot of potato, tuber slices were treated with T-2 toxin, followed by the inoculation with F. sulphureum spores. Results in this study showed that the reduction of disease area was linked with higher abundance of reactive oxygen species (ROS) and new phenylpropanoid metabolites. T-2 toxin treatment increased ROS accumulation and induced the activities of enzymes involved in ROS and phenylpropanoid metabolism. At the same time, T-2 toxin treatment also up-regulated proteins involved in ROS and phenylpropanoid metabolism determined by iTRAQ (isobaric tags for relative and absolute quantitation) assay, as well as genes encoding proteins involved ROS and phenylpropanoid metabolism. Taken together, this study provides substantial evidences that T-2 toxin induced resistance related proteins and genes in potato tuber slices to suppress the dry rot severity of F. sulphureum. [ABSTRACT FROM AUTHOR]

The present article describes the synthesis, in vitro urease inhibition and in silico molecular docking studies of a novel series of bi-heterocyclic bi-amides. The synthesis of title compounds was initiated by benzoylation, with benzoyl chloride ( 1 ), of the key starter ethyl 2-(2-amino-1,3-thiazol-4-yl)acetate ( 2 ) in weak basic aqueous medium followed by hydrazide formation, 4 , and cyclization with CS 2 to reach the parent bi-heterocyclic nucleophile, N -{4-[(5-sulfanyl-1,3,4-oxadiazol-2-yl)methyl]-1,3-thiazol-2-yl}benzamide ( 5 ). Various electrophiles, 8a–l , were synthesized by a two-step process and these were finally coupled with 5 to yield the targeted bi-heterocyclic bi-amide molecules, 9a–l . The structures of the newly synthesized products were corroborated by IR, 1 H NMR, 13 C NMR, EI-MS and elemental analysis. The in vitro screening of these molecules against urease explored that most of the compounds exhibit potent inhibitory potential against this enzyme. The compound 9j , with IC 50 value of 2.58 ± 0.02 µM, exhibited most promising inhibitory activity among the series, relative to standard thiourea having IC 50 value of 21.11 ± 0.12 µM. In silico studies fully augmented the experimental enzyme inhibition results. Chemo-informatics analysis showed that synthesized compounds ( 9a–l ) mostly obeyed the Lipinski's rule. Molecular docking study suggested that ligand 9j exhibited good binding energy value (−7.10 kcal/mol) and binds within the active region of target protein. So, on the basis of present investigation, it was inferred that 9j may serve as a novel scaffold for designing more potent urease inhibitors. [ABSTRACT FROM AUTHOR]

To seek the new medicinal potential of sulfadiazine drug, the free amino group of sulfadiazine was exploited to obtain acyl/aryl thioureas using simple and straightforward protocol. Acyl/aryl thioureas are well recognized bioactive pharmacophore containing moieties. A new series ( 4a – 4j ) of sulfadiazine derived acyl/aryl thioureas was synthesized and characterized through spectroscopic and elemental analysis. The synthesized derivatives 4a – 4j were subjected to calf intestinal alkaline phosphatase (CIAP) activity. The derivative 4a – 4j showed better inhibition potential compared to standard monopotassium phosphate (MKP). The compound 4c exhibited higher potential in the series with IC 50 0.251 ± 0.012 µM (standard KH 2 PO 4 4.317 ± 0.201 µM). Lineweaver-Burk plots revealed that most potent derivative 4c inhibition CIAP via mixed type pathway. Pharmacological investigations showed that synthesized compounds 4a – 4j obey Lipinsk’s rule. ADMET parameters evaluation predicted that these molecule show significant lead like properties with minimum possible toxicity and can serve as templates in drug designing. The synthetic compounds show none mutagenic and irritant behavior. Molecular docking analysis showed that compound 4c interacts with Asp273, His317 and Arg166 amino acid residues. [ABSTRACT FROM AUTHOR]

• Ca2+ significantly inhibited the development of dry rot and weigh loss rate. • Ca2+ influenced the accumulations of suberin polyphenolic and suberin polyaliphatic. • Ca2+ affected enzymatic activity and gene expression of phenylpropanoid metabolism. • Ca2+ significantly improved the accumulation of phenylpropanoid metabolites. The dry rot of potato caused by Fusarium sulphureum is the main postharvest disease that causes serious economic loss and leads to mycotoxin contamination. Therefore, it is necessary to find a strategy to increase the plant's resistance against disease. T-2 toxin at low concentration can act as an elicitor to induce resistance against disease. Calcium ion plays a vital role in induced resistance by responding the environmental stress in plant. In this study, the effect of Ca2+ on the development of dry rot, weight loss rate, the suberin polyphenolic (SPP) and suberin polyaliphatic (SPA) accumulation and their participation in phenylpropanoid metabolism were investigated in treated potato. The results showed that lesion diameter and weight loss rate significantly increased after ethylenebis (oxyethylenenitrilo) tetraacetic acid (EGTA) treatment, but the addition of exogenous Ca2+ noticeably inhibited the increase. The accumulations of SPP and SPA, enzymatic activities, gene expressions, as well as the contents of total phenols and lignin and their major substrates involved in phenylpropanoid metabolism were decreased after EGTA treatment, these indicators were recovered after the addition of exogenous Ca2+. Therefore, the results suggested that Ca2+ treatment induced resistance against dry rot, inhibited weight loss rate and accelerated the accumulation of SPP and SPA by activating phenylpropanoid metabolism in treated potato. [ABSTRACT FROM AUTHOR]

[Display omitted] • A series of the 1,3,4-oxadiazole based derivatives were synthesized. • All the oxadiazole compounds demonstrate good tyrosinase inhibitory activity. • Among the series, 2-(5-(2-methoxyphenyl)-1,3,4-oxadiazol-2-ylthio)- N -phenylacetamide exhibit more potent activity than standard drug. • Most potent compound exhibit non-toxic behavior against B16F10 melanoma cells. • The in-vitro results are in support of molecular docking studies. In this research work, we have designed and synthesized some biologically useful of 1,3,4-Oxadiazoles. The structural interpretation of the synthesized compounds has been validated by using FT-IR, LC-MS, HRMS, 1H NMR and 13C NMR techniques. Moreover, the in-vitro mushroom tyrosinase inhibitory potential of the target compounds was assessed. The in-vitro study reveals that, all compounds demonstrate an excellent tyrosinase inhibitory activity. Especially, 2-(5-(2-methoxyphenyl)-1,3,4-oxadiazol-2-ylthio)- N -phenylacetamide (IC 50 = 0.003 ± 0.00 µM) confirms much more significant potent inhibition activity compared with standard drug kojic acid (IC 50 = 16.83 ± 1.16 µM). Subsequently, the most potent five oxadiazole compounds were screened for cytotoxicity study against B16F10 melanoma cells using an MTT assay method. The survival rate for the most potent compound was more pleasant than other compounds. Furthermore, the western blot results proved that the most potent compound considerably decreased the expression level of tyrosinase at 50 µM (P < 0.05). The molecular docking investigation exposed that the utmost potent compound displayed the significant interactions pattern within the active region of the tyrosinase enzyme and which might be responsible for the decent inhibitory activity towards the enzyme. A molecular dynamic simulation experiment was presented to recognize the residual backbone stability of protein structure. [ABSTRACT FROM AUTHOR]