Antioxidant Activity and Molecular Docking Study of Volatile Constituents from Different Aromatic Lamiaceous Plants Cultivated in Madinah Monawara,Saudi Arabia

A comparative study of volatile constituents, antioxidant activity, and molecular docking was conducted between essential oils from Mentha longifolia L., Mentha spicata L., and Origanum majorana L., widely cultivated in Madinah. The investigation of volatile oils extracted by hydrodistillation was performed using Gas Chromatography-Mass Spectrometry (GC-MS). A total number of 29, 42, and 29 components were identified in M. longifolia, M. spicata, and O. majorana representing, respectively, 95.91, 94.62, and 98.42, of the total oils. Pulegone (38.42%), 1,8-cineole (15.60%), menthone (13.20%), and isopulegone (9.81%) were the dominant compounds in M. longifolia oil; carvone (35.14%), limonene (27.11%), germacrene D (4.73%), and β-caryophyllene (3.02%) were dominant in M. spicata oil; terpin-4-ol (42.47%), trans-sabinene hydrate (8.52%), γ-terpinene (7.90%), α-terpineol (7.38%), linalool (6.35%), α-terpinene (5.42%), and cis-sabinene hydrate (3.14%) were dominant in O. majorana oil. The antioxidant activity, assessed using DPPH free radical–scavenging and ABTS assays, was found to be the highest in O. majorana volatile oil, followed by M. spicata and M. longifolia, which is consistent with the differences in total phenolic content and volatile constituents identified in investigated oils. In the same context, molecular docking of the main identified volatiles on NADPH oxidase showed a higher binding affinity for cis-verbenyl acetate, followed by β-elemene and linalool, compared to the control (dextromethorphan). These results prove significant antioxidant abilities of the investigated oils, which may be considered for further analyses concerning the control of oxidative stress, as well as for their use as possible antioxidant agents in the pharmaceutical industry.     

Microwave-Assisted One Pot Three-Component Synthesis of Novel Bioactive Thiazolyl-Pyridazinediones as Potential Antimicrobial Agents against Antibiotic-Resistant Bacteria

Pyridazine and thiazole derivatives have various biological activities such as antimicrobial, analgesic, anticancer, anticonvulsant, antitubercular and other anticipated biological properties. Chitosan can be used as heterogeneous phase transfer basic biocatalyst in heterocyclic syntheses. Novel 1-thiazolyl-pyridazinedione derivatives were prepared via multicomponent synthesis under microwave irradiation as ecofriendly energy source and using the eco-friendly naturally occurring chitosan basic catalyst with high/efficient yields and short reaction time. All the prepared compounds were fully characterized by spectroscopic methods, and their in vitro biological activities were investigated. The obtained results were compared with those of standard antibacterial/antifungal agents. DFT calculations and molecular docking studies were used to investigate the electronic properties and molecular interactions with specific microbial receptors.     

Simulation-based framework to improve patient experience in an emergency department

The global economic crisis has a significant impact on healthcare resource provision worldwide. The management of limited healthcare resources is further challenged by the high level of uncertainty in demand, which can lead to unbalanced utilization of the available resources and a potential deterioration of patient satisfaction in terms of longer waiting times and perceived reduced quality of services. Therefore, healthcare managers require timely and accurate tools to optimize resource utility in a complex and ever-changing patient care process. An interactive simulation-based decision support framework is presented in this paper for healthcare process improvement. Complexity and different levels of variability within the process are incorporated into the process modeling phase, followed by developing a simulation model to examine the impact of potential alternatives. As a performance management tool, balanced scorecard (BSC) is incorporated within the framework to support continual and sustainable improvement by using strategic-linked performance measures and actions. These actions are evaluated by the simulation model developed, whilst the trade-off between objectives, though somewhat conflicting, is analysed by a preference model. The preference model is designed in an interactive and iterative process considering decision makers preferences regarding the selected key performance indicators (KPIs). A detailed implementation of the framework is demonstrated on an emergency department (ED) of an adult teaching hospital in north Dublin, Ireland. The results show that the unblocking of ED outflows by in-patient bed management is more effective than increasing only the ED physical capacity or the ED workforce.     

Synthesis and antimicrobial activity of some heterocyclic 2,6‐bis(substituted)‐1,3,4‐thiadiazolo‐, oxadiazolo‐, and oxathiazolidino‐pyridine derivatives from 2,6‐pyridine dicarboxylic acid dihydrazide

In this work, we report on the synthesis and preliminary biological activity screening of several heterocyclic derivatives 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 10a , 10b , 11 , 11a , 11b , 12 , 12a , 12b , 13 , 13a , 13b , 14 , 15 based on N2′,N6′‐diphenylthiosemi‐carbazide pyridine‐2,6‐dicarbohydrazide 2 , which has been obtained from the corresponding dihydrazide 1 . The biological screening showed that many of these compounds have good antimicrobial activities. The structure of the new compounds has been established on the bases of chemical and spectroscopic evidences. J. Heterocyclic Chem., (2011).     

Synthesis and Anti-Inflammatory Activities of Some Novel S-Pyridyl Glycosides Derivatives

A series of some new acetylated S-glycosides of pyridine-2-thione derivatives, including D-glucose, D-galactose, D-xylose and L-arabinose derivatives were synthesized. Oxidation of some formed S-glycosides derivatives with H₂O₂ afforded the corresponding sulfones. S-Alkylation of pyridine-2-thione derivatives was performed to furnish the S-acyclo deazauridine derivatives. The entire tested compound showed potent anti-inflammatory activity were potent against edema and in the same time inhibited the prostaglandine formation. It is work mention that all the tested compounds showed high safety margin. The structures of the new synthesized compounds have been proved by IR, ¹ HNMR, mass spectra and elemental analysis.     

Regiospecific synthesis of novel spiro-pyrimidobarbiturates with promising antibacterial activities

In this work, a novel series of 9-amino-7-aryl-11-imino-2,4,8,10-tetraazaspiro[5.5]undeca-7,9-diene-1,3,5-triones 3a-l was synthesized via the treatment of cyanoguanidine 1 with respective arylidene barbituric acids 2a-l in dry pyridine. The products were evaluated for in vitro antibacterial activity against Bacillus cereus (+G), Staphylococcus aureus (+G), Pseudomonas aeruginosa (−G) and Escherichia coli (−G). The results showed that some of the tested products are promising antibacterial drugs.     

Saffron and Its Major Ingredients’ Effect on Colon Cancer Cells with Mismatch Repair Deficiency and Microsatellite Instability

Background: Colorectal cancer (CRC) is one of the most common cancers worldwide. One of its subtypes is associated with defective mismatch repair (dMMR) genes. Saffron has many potentially protective roles against colon malignancy. However, these roles in the context of dMMR tumors have not been explored. In this study, we aimed to investigate the effects of saffron and its constituents in CRC cell lines with dMMR. Methods: Saffron crude extracts and specific compounds (safranal and crocin) were used in the human colorectal cancer cell lines HCT116, HCT116+3 (inserted MLH1), HCT116+5 (inserted MSH3), and HCT116+3+5 (inserted MLH1 and MSH3). CDC25b, p-H2AX, TPDP1, and GAPDH were analyzed by Western blot. Proliferation and cytotoxicity were analyzed by MTT. The scratch wound assay was also performed. Results: Saffron crude extracts restricted (up to 70%) the proliferation in colon cells with deficient MMR (HCT116) compared to proficient MMR. The wound healing assay indicates that deficient MMR cells are doing better (up to 90%) than proficient MMR cells when treated with saffron. CDC25b and TDP1 downregulated (up to 20-fold) in proficient MMR cells compared to deficient MMR cells, while p.H2AX was significantly upregulated in both cell types, particularly at >10 mg/mL saffron in a concentration-dependent manner. The reduction in cellular proliferation was accompanied with upregulation of caspase 3 and 7. The major active saffron compounds, safranal and crocin reproduced most of the saffron crude extracts’ effects. Conclusions: Saffron’s anti-proliferative effect is significant in cells with deficient MMR. This novel effect may have therapeutic implications and benefits for MSI CRC patients who are generally not recommended for the 5-fluorouracil-based treatment.     

Synthesis and anti-viral activities of some 3-(naphthalen-1-ylmethylene)-5-phenylfuran-2(3H)-one candidates

3-(Naphthalen-1-ylmethylene)-5-phenylfuran-2(3H)-one 1 was prepared and converted into a variety of heterocyclic systems of synthetic and biological importance. Benzylamine was reacted with furanone 1 to afford compounds 2 and 3 according to the reaction conditions. Butanamide 2 was reacted with thionyl chloride or thiourea to give derivatives 4 and 5, respectively. Compound 3 was reacted with ethyl cyanoacetate to give the corresponding pyrrolopyridine derivative 6. Treatment of 1 with hydrazine hydrate afforded compounds 7 and 8 according to the reaction conditions. Also, compound 1 was reacted with phenyl hydrazine, hydroxyl amine, malononitrile or thiourea to give compounds 9–12, respectively. Cyclization of 7 with ethoxymethylene-malononitrile, ethyl-(ethoxymethylene)cyanoacetate, carbon disulphide or acetylacetone afforded the corresponding compounds 13–16, respectively. Condensation of 7 with p-nitrobenzaldehyde gave the corresponding hydrazone 17, which was treated with thioglycolic acid or chloroacetyl chloride to give compounds 18 and 19, respectively. Also, most of the prepared products were tested for anti-avian influenza virus and revealed promising antiviral activity against H5N1 virus [A/Chicken/Egypt/1/2006 (H5N1)] by determination of both TC ₅₀ and ED ₅₀ and confirmed by plaque reduction assay on MDCK cells. Compounds 7, 8, 11, 12 and 13 showed the highest effect compared with the other tested compounds.     

Nitrite-Mediated Inactivation of Human Plasma Paraoxonase-1: Possible Beneficial Effect of Aromatic Amino Acids

Paraoxonase-1 (PON-1) is a high-density-lipoprotein-bound enzyme, and its major function is to prevent oxidation of low-density lipoprotein. Atherogenesis could be related to decreased activity of this enzyme. Nitrites (), either present as a contaminant and/or the main metabolic end product of nitric oxide (NO) degradation, may trigger nitrative damage to PON-1 enzyme. Minimal information is available concerning the effect of nitrite on the enzyme activity and the mechanism which it exerts its effect. The aim of this study was to analyze whether nitrites could play a role in modifying human PON-1 activity. Our results revealed that PON-1 activity was inhibited by nitrite in dose- and time-dependent manner. Site-specific nitration focused on phenolic residues, particularly tyrosine residues of the enzyme, may result in modification of its biological functions. Nitration of phenolic residues occurs via peroxynitrite (ONOO⁻) formation, which requires peroxides and nitrite. Thus, we tested the presence of peroxides, which are found in all plasma samples regardless of nitrite concentration. The inhibition of PON-1 activity by nitrite was significantly reduced by tryptophan, reduced glutathione (GSH), and catalase additions. Therefore, we concluded that nitrites may have a role in the inactivation of PON-1, probably through nitration of enzyme phenyl residues, and additions of individual aromatic amino acids, with highlighting on tryptophan, could be of important value in minimizing the nitrite-induced inhibition of PON-1 enzyme.     

Analysis of a Polynomial System Arising in the Design of an Optical Lattice Filter Useful in Channelization

In this work, we consider design questions for an active optical lattice filter, which is being manufactured at the University of Texas at Dallas, and which has proven to be useful in the signal processing task of RF channelization. The filter can be described by a linear, discrete time state space model. The controlling agents, the gains, are embedded in the matrices intervening in this state space model. Consequently, techniques from linear feedback control theory do not apply. We concentrate on the question of finding real valued gains so that the A matrix of the state space model has a prescribed characteristic polynomial. We find that three of the coefficients can be arbitrarily picked, but that the remaining are constrained by these and the other system parameters. Our techniques use methods from constructive algebraic geometry.