Series Of Hybrids Research Articles

Organizational fashion and trend setting in the hospitality industry

PurposeThis study aims to use organizational fashion to underscore a novel phenomenon in which products, services and practices fade in and out of the tourism/hospitality setting within a specific time frame. Drawing from the fashion theoretical strands in organization research, this paper studies how fashion has been conceptualized, operationalized and then diffused among tourism/hospitality enterprises.Design/methodology/approachA qualitative case design was used. A total of 37 semistructured in-depth interviews with executives of innovative tourism/hospitality companies (e.g. restaurants, hotels, theme parks and travel agencies) were conducted. This paper focuses on the organizational fashion phenomenon in which organizational trendsetters with creative, “hot” products/services have emerged prominently in the marketplace.FindingsThis inquiry illustrates a social phenomenon concerning the organizational fashion setting process by integrating existing production practices among different organizational suppliers in the hospitality sector. Different cases in the study show that fashion consists of a series of hybrid, paradoxical processes. These include conceptualization (conventionalization vs novelty, and personalization vs conformity), operationalization (bundling vs unbundling, and learning vs relearning) and diffusion (framing vs co-framing, and adaptation vs alteration).Research limitations/implicationsThroughout the three continuous processes, service design and identity development for consumption, as well as value creation and knowledge transformation for production, are carried out according to the decision of what is “hot” and what is “out” at a particular time. In essence, fashion helps to explain why hospitality institutions imitate specific innovations to take advantage of popular trends in the consumer market, as well as how such trends vanish eventually.Originality/valueThis research contributes the insight that organizations use fashion as a managerial initiative to translate their organizational goals and improvise nascent products and services. The fashion processes can be triggered by microlevel individual organizations and are spread through a series of social interactions to become macrolevel phenomena in a recurring manner.

Performance Analysis of Novel Solar PV Array Configurations with Reduced Tie Interconnection to Extract Maximum Power under Partial Shading

The non-uniform irradiation pattern causes the partial shading effects and decreases the performance of the solar Photovoltaic (PV) array. The effect of uneven shading condition depends on its pattern and area. The PV array’s performance is determined by the cross ties that are connected within the array. This research proposes eight different PV array tie interconnection configurations to obtain the maximum power output under uneven insolation conditions. Experimental analysis is done in the PV array consists of 16 numbers of 10 W PV panels which has a total capacity of 160 W. The practical results reveal that the losses due to partial shading are influenced by the shade pattern, shade area, and the placement of the cross ties. Overall, among the conventional configurations, the hybrid bridge link total cross tied interconnection pattern produced the best results, followed by the hybrid series parallel total cross tied and bridge link patterns. In the proposed configurations, the plus tie configuration outperformed the others in maximum of the partial shading scenarios. In general, the PLT configuration demonstrated an average power efficiency increase of 19.17%, 8.37%, and 8.28% compared to the series parallel, hybrid series parallel total cross-tied, bridge link, and bridge link total cross-tied configurations, respectively. The effectiveness of the proposed configurations is validated by the practical verifications.

Luminescent Hybrid BPA.DA-NVP@Eu2L3 Materials: In Situ Synthesis, Spectroscopic, Thermal, and Mechanical Characterization.

A series of homogeneous hybrid BPA.DA-NVP@Eu2L3 materials were obtained through an in situ approach where the luminescent dopant was formed at the molecular level with different contents (0.1; 0.2; 0.5; 1; and 2% by weight). A Europium(III) complex (Eu2L3) with quinoline-2,4-dicarboxylic acid was applied as a luminescence additive while a polymer matrix consisted of a combination of bisphenol A diacrylate (BPA.DA) and N-vinylpyrrolidone (NVP) monomers. Synthesis steps and the final materials were monitored by NMR and Fourier transform infrared spectroscopy (FTIR). The emission, excitation spectra, lifetime, and quantum yield measurements were applied for the determination of the photophysical characteristics. The thermal and mechanical properties of the obtained materials were tested via thermal analysis methods (TG/DTG/DSC and TG-FTIR) in air and nitrogen atmospheres, dynamic mechanical analysis (DMA), and hardness and bending measurements. Generally, even a small addition of the metal complex component causes changes in the thermal, mechanical, and luminescent properties. Hybrid materials with a greater europium complex content are characterized by a lower stiffness and hardness while the heterogeneity and the flexibility of the samples increase. A very small amount of an Eu2L3 admixture (0.1% wt.) in a hybrid material causes an emission in the red spectral range and the luminescence intensity was reached for the BPA-DA-NVP@1%Eu2L3 material. These materials may be potentially used in chemical sensing, security systems, and protective coatings against UV.

Galantamine-memantine hybrids for Alzheimer's disease: The influence of linker rigidity in biological activity and pharmacokinetic properties

Neurodegenerative processes characterizing Alzheimer's disease (AD) are strictly related to the impairment of cholinergic and glutamatergic neurotransmitter systems which provoke synaptic loss. These experimental evidences still represent the foundation of the actual standard-of-care treatment for AD, albeit palliative, consisting on the coadministration of an acetylcholinesterase inhibitor and the NMDAR antagonist memantine. In looking for more effective treatments, we previously developed a series of galantamine-memantine hybrids where compound 1 (ARN14140) emerged with the best-balanced action toward the targets of interest paired to neuroprotective efficacy in a murine AD model. Unfortunately, it showed a suboptimal pharmacokinetic profile, which required intracerebroventricular administration for in vivo studies. In this work we designed and synthesized new hybrids with fewer rotatable bonds, which is related to higher brain exposure. Particularly, compound 2, bearing a double bond in the tether, ameliorated the biological profile of compound 1 in invitro studies, increasing cholinesterases inhibitory potencies and selective antagonism toward excitotoxic-related GluN1/2B NMDAR over beneficial GluN1/2A NMDAR. Furthermore, it showed increased plasma stability and comparable microsomal stability in vitro, paired with lower half-life and faster clearance in vivo. Remarkably, pharmacokinetic evaluations of compound 2 showed a promising increase in brain uptake in comparison to compound 1, representing the starting point for further chemical optimizations.

Synthesis of New Coumarin-C3 Benzimidazole Hybrids and Their Urease Inhibition Studies

Abstract: A novel series of coumarin-benzimidazole hybrids were designed, synthesized, and extensively characterized using spectral data, including FT-IR, 1H-NMR, and 13C-NMR. Weatherburn's method was used to test new compounds' inhibition of urease activity. The results were evaluated by considering the effects of different side groups and hybridization. The chlorine atom in the molecules notably affects the inhibitory activity of urease. The best result was obtained with the compound “6- chloro-N'-{[5,6-dichloro-2-(2-thienylmethyl)-1H-benzimidazol-1-yl]acetyl}-2-oxo-2H-chromene-3- carbohydrazide” (3b) with IC50= 12.48±0.12 μg/mL against Jack bean urease.

Pyrrole-thiazolidinone hybrids as a new structural class of broad-spectrum anti-infectives

A series of pyrrole-thiazolidinone hybrids was designed, synthesized and evaluated for activities against ESKAP bacteria panel and mycobacterial pathogens. From the series, compound 9d showed prominent activity against S. aureus (MIC = 0.5 μg/mL) and compound 9k showed the most promising activity against M. tuberculosis H37Rv (MIC = 0.5 μg/mL). Potent derivatives were found to be non-toxic when tested against Vero cells. Compound 9d upon evaluation in vitro against several MRSA and VRSA strains produced activity comparable or better than standard drugs. In the anti-biofilm assay, 9d reduced S. aureus biofilm by >11% at 10x MIC. The dual inhibitory effect exhibited by pyrrole-thiazolidinone hybrids confirms their potential as new class of promising anti-infective agents.

Novel pyridine-thiazolidinone-triazole hybrid glycosides targeting EGFR and CDK-2: Design, synthesis, anticancer evaluation, and molecular docking simulation

The observed toxicity of newly designed anticancer drugs is considered as an impediment challenging phenomenon of intense concern arising from diversity in drug targets and the latter concern is therefore still in need for further research. The current investigation reports the design and synthesis of a new series of pyridine-thiazole hybrids and their derived 1,2,3-triazole analogues incorporating with varied sugar moieties and their acyclic analogues 3–11 and 13–18. The newly synthesized compounds were investigated for their cytotoxic activities against human liver HepG-2 and breast MCF-7 cancer cell lines. The pyridine-thiazolidinone-triazole based targets 16–18 revealed the potent cytotoxic activities. Also, all synthesized derivatives afforded promising safety antiproliferative margins against the normal human diploid cell line WI-38. The promising analogues 16–18 were further studied for their inhibitory assessment against EGFR and CDK-2/cyclin A2 kinases. The pyridine-thiazolidinone-1,2,3-triazole based glycosides 17 and 18 displayed promising and relatively equipotent inhibitory activity against EGFR enzyme compared with the reference drug, erlotinib (IC50= 0.19, 0.12, and 0.15 μM, respectively). While, the three glycosides 16–18 showed superior inhibitory potency against CDK-2/cyclin A2 kinases compared to the standard roscovitine (IC50 = 0.26, 0.22, 0.18 and 0.42 μM, respectively). The impact of triazole glycoside 18 upon cell cycle and apoptosis induction was determined to detect its mechanism of action. Additionally, it upregulated the levels of caspase-3, Bax and Bcl-2 in MCF-7 cells. Finally, molecular docking study was simulated to achieve a better rationalization and gain an insight into the binding affinity of the potent derivatives with their targeted enzymes, which prompts their application as optimum leads for further modification in the anticancer field.

Design, Synthesis, Molecular Docking and Cytotoxicity of Stilbene-arylcinnamide Hybrids on A549 Lung Cancer Cells

Abstract: A new series of stilbene-arylcinnamide hybrids have been designed and synthesized with various substituents. These compounds were characterized by FTIR, 1D- and 2D-NMR as well as mass spectroscopy analysis (HRESIMS). The synthesized compounds were tested for their cytotoxic activity against human lung cancer A549 cell. The most active compound was further studied via in silico molecular docking on α,β- interface of tubulin. Total 18 new stilbene-arylcinnamide hybrids have been synthesized with 42-80% yield and evaluated for their cytotoxic activity against human lung cancer A549 cell. Particularly, compound 6b exhibited potent cytotoxicity against A549 cells with the IC50 value of 19.9 μM. In addition, compound 7b displayed moderate activities with the IC50 value of 33.9 μM, while other hybrids were considered inactive. Structural activity relationship (SAR) studies revealed that the presence of an isopropyl group at the para position on ring A and a methyl group at the para position on ring C is beneficial for enhanced cytotoxicity. Furthermore, we also developed an in silico molecular docking to study the binding interaction of the active compounds to the α,β-interface of tubulin (PDB ID: 3E22). Hybrids 6b and 7b demonstrated promising binding interactions and affinities into the tubulin active site with calculated binding energy of -7.2 and -8.0 kcal/mol, respectively.

Synthesis and biological evaluation of coumarin appended thiazole hybrid heterocycles: Antibacterial and antifungal study

In the present investigation, a series of 3-(1-(2-(thiazol-2-yl)hydrazineylidene)ethyl)-2H-chromen-2-one derivatives are synthesized in good to excellent yield using PEG-400 as a reaction medium. The synthesized compounds are characterized by using different spectroscopic methods like FT-IR, 1H NMR, 13CMR, and HRMS. In this study, the synthesis and biological evaluation of a series of coumarin-appended thiazole hybrids were explored to assess their antibacterial and antifungal properties. Antibacterial activity of the synthesized coumarin-thiazole hybrids was screened against E. coli, P. aeruginosa, S. aureus, and S. pyogenes strains, while antifungal activity was screened against C. albicans, A. niger, and A. clavatus strains. Some of the synthesized compounds showed good antibacterial activity against E. coli and P. aeruginosa strains compared to standard drugs. The ADME profile of these compounds showed favorable pharmacological properties.

Development of novel celastrol-ligustrazine hybrids as potent peroxiredoxin 1 inhibitors against lung cancer

The disruption of oxidation-reduction equilibrium through inhibiting reactive oxygen species (ROS) clearance or enhancing ROS production has emerged as a novel and promising strategy for cancer therapy. Herein, a series of celastrol-ligustrazine hybrids were designed and synthesized as effective ROS promoters, and their biological activities were further evaluated. Among them, compound 7e stood out as the most potent peroxiredoxin 1 (PRDX1) inhibitor (IC50 = 0.164 μM), which was significant super to the recognized PRDX1 inhibitor Conoidin A (IC50 = 14.80 μM) and the control compound celastrol (IC50 = 1.622 μM). Furthermore, 7e dramatically promoted intracellular ROS accumulation, and inhibited the proliferation, invasion and migration of cancer cells besides inducing apoptosis in vitro. Additionally, 7e suppressed the key signaling pathways (AKT and ERK) and promoted the expression of apoptosis-related proteins (cleaved caspase-3/8 and cleaved PARP) in A549 cells, which resulted in the prevention of tumor progression. Most importantly, compound 7e (TGI = 77.47%) showed more considerable in vivo antitumor efficacy and less toxicity than celastrol (TGI = 71.00%). Overall, this work indicates 7e as the most potential PRDX1 inhibitor and may be a promising candidate for the therapy of lung cancer.

Discovery of novel series of 4-quinolone hybrids as multi-targeting agent: Design, synthesis and H1-antihistaminic activity to treat allergic asthma

Discovery of novel series of 4-quinolone hybrids as multi-targeting agent: Design, synthesis and H1-antihistaminic activity to treat allergic asthma

Film formation of high poly(vinyl chloride) content latex particles

Although poly(vinyl chloride) (PVC) is produced on a large scale industrially by emulsion and suspension polymerization, it is usually processed from the dry state and is seldom directly used as an aqueous polymer dispersion. In this work we demonstrate that by control of particle morphology and particle size distribution it is possible to produce latexes with high PVC content from which polymer films can be cast directly. A series of hybrid PVC/acrylic latexes with a core-shell structure are produced by semi-batch emulsion polymerization using a preformed PVC latex as a seed. Although monomodal particles of this type have a minimum film formation temperature in excess of 80 °C when the content of PVC is high, it is shown that through the use of a bimodal particle size distribution the packing efficiency of the spherical PVC domains is increased such that room temperature film formation is possible with PVC content up to 80 wt%.

Three-dimensional electrodes in hybrid electrolytes for high-loading and long-lasting calcium-ion batteries

Aqueous calcium-ion batteries (CIBs) exhibit a reliable long-term cycling and rate performance, but they have a low energy density owing to the narrow electrochemical stability window (ESW) of aqueous electrolytes. Highly concentrated water-in-salt electrolytes offer enhanced stability by limiting the number of free water molecules present within the system. However, CIB electrolytes still suffer from low conductivity and high viscosity due to the high concentration of calcium salt. Hence, to resolve this problem, a series of hybrid aqueous/organic calcium electrolytes were formulated to improve the ESW and long-term reversibility while maintaining a low electrolyte concentration. The best hybrid-electrolyte candidate, which had a calcium perchlorate/water/acetonitrile molar ratio of 1.0:4.0:4.8 (i.e., Ca(ClO4)2/(H2O)4.0(AN)4.8), exhibited a wide ESW (≈3.0 V) and a facile insertion of calcium ions into Prussian green host materials, leading to an impressive 90% capacity retention after 1000 cycles. Nickel foam (NF) was also employed as a cathode current collector to investigate the feasibility of the drop-coated three-dimensional electrodes. Owing to its high-porosity architecture, the NF substrate could accommodate for four to eight times higher mass loading than traditional foil-type collectors, resulting in full cells with much higher energy densities.

Discovery of tetrahydroisoquinolineindole derivatives as first dual PRMT5 inhibitors/hnRNP E1 upregulators: Design, synthesis and biological evaluation

Protein arginine methyltransferase 5 (PRMT5) is an epigenetics related enzyme that has been validated as an important therapeutic target for treating various types of cancer. Upregulation of tumor suppressor hnRNP E1 has also been considered as an effective antitumor therapy. In this study, a series of tetrahydroisoquinolineindole hybrids were designed and prepared, and compounds 3m and 3s4 were found to be selective inhibitors of PRMT5 and upregulators of hnRNP E1. Molecular docking studies indicated that compounds 3m occupied the substrate site of PRMT5 and formed essential interactions with amino acid residues. Furthermore, compounds 3m and 3s4 exerted antiproliferative effects against A549 cells by inducing apoptosis and inhibiting cell migration. Importantly, silencing of hnRNP E1 eliminated the antitumor effect of 3m and 3s4 on the apoptosis and migration in A549 cells, suggesting a regulatory relationship between PRMT5 and hnRNP E1. Additionally, compound 3m exhibited high metabolic stability on human liver microsomes (T1/2 = 132.4 min). In SD rats, the bioavailability of 3m was 31.4%, and its PK profiles showed satisfactory AUC and Cmax values compared to the positive control. These results suggest that compound 3m is the first class of dual PRMT5 inhibitor and hnRNP E1 upregulator that deserves further investigation as a potential anticancer agent.

Discovery of novel hybrids of mTOR inhibitor and NO donor as potential anti-tumor therapeutics

Nitric oxide (NO) may be beneficial to overcoming drug resistance resulting from mutation of mTOR kinases and bypass mechanisms. In this study, a novel structural series of hybrids of mTOR inhibitor and NO donor were designed and synthesized via structure-based drug design (SBDD). Throughout the 20 target compounds, half of the compounds (13a, 13b, 19a-19d, 19f-19j) demonstrated attractive mTOR inhibitory activity with IC50 at single-digit nanomolar level. In particular, 19f exerted superior anti-proliferative activity against HepG2, MCF-7, HL-60 cells (HepG2, IC50 = 0.24 μM; MCF-7, IC50 = 0.88 μM; HL-60, IC50 = 0.02 μM) to that of the clinical investigated mTOR inhibitor MLN0128, and show mild cytotoxicity against normal cells with IC50 over 10 μM. 19a, with the most potent mTOR inhibitory activity in this series (IC50 = 3.31 nM), also displayed attractive cellular potency. In addition, 19f treatment in HL-60 reduces the levels of Phos-Akt and Phos-S6 in a dose-dependent manner, and releases NO in cells. In summary, 19f deserves further development as a novel mTOR-based multi-target anti-cancer agent.

Synthesis of Hybrid Isoxazole‐triazole Compounds as Potential Antiproliferative Agents

AbstractAn efficient route for the synthesis of a series of new hybrid isoxazole‐triazole compounds in high yields and excellent regioselectivity starting from either 2‐aryl‐1,1‐dichlorocyclopropanes or N‐hydroxybenzimidoyl chlorides was developed. The synthesized isoxazole‐triazole hybrids were evaluated for their biological activity.

Versatile Bifunctional Ag@g-C3N4/r-GO Catalyst for Efficient Photo- and Electrocatalytic H2 Production

Here, we develop a series of hybrid Ag@g-C3N4/r-GO nanocomposite materials that are highly active, durable, and adaptable for electro- and photocatalytic H2 generation under visible light by employing a rapid and simple sonochemical technique. Multiple catalytic behaviors can be achieved through the strategic introduction of Ag metal into a hierarchical structure consisting of photo- and electroactive two-dimensional (2D) sheets with various band configurations. The outcomes of this work show the development of heterojunctions and show how electro- and photocatalysis were both synergistically improved. The fabricated materials were examined for photocatalytic hydrogen evolution, photoelectrocatalytic (PEC) hydrogen evolution, and electrocatalytic hydrogen evolution reaction (HER). In both photocatalytic conditions at 1.5 AM simulated light irradiation and electrocatalytic conditions, silver-doped composites showed better activity. Among all of the fabricated catalysts, the Ag20%@g-C3N4/r-GO (A20CNG) catalyst displayed the highest apparent quantum yield (AQY) of 1.69 and the highest hydrogen generation rate (954 μmol g–1 h–1). However, in the case of electrocatalysis, Ag15%@g-C3N4/r-GO (A15CNG) showed impressive HER activity with a low overpotential (η) of 0.484 V at 10 mA cm–2 current density with 130.6 mV dec–1 Tafel slope value and also exhibited approximately 16 times more current density than that of g-C3N4/GO (CNGO) at a fixed overpotential in the HER process; this was also supported by the electrochemical active surface area (ECSA). On the basis of the impressive results shown above, the Ag@g-C3N4/r-GO (ACNG) catalyst might be a promising and flexible nanocomposite for photo-, photoelectro-, and electrocatalytic hydrogen evolutions. This is the first study to our knowledge that provides the results of a comprehensive examination into the photo- and electrocatalytic application of an interesting and versatile bifunctional catalyst.

A green synthesis, DFT calculations, and molecular docking study of some new indeno[2,1-b]quinoxalines containing thiazole moiety

A series of new indenoquinoxaline-thiazole hybrids were synthesized by combining indenoquinoxaline thiosemicarbazone with appropriate hydrazonoyl chlorides or α-halo ketones using DABCO as a catalyst. The short reaction times and excellent yields make this method simple, green, and economic to synthesize new compounds with potential biological activities. FT IR, NMR, and MS spectrum data are some of the spectroscopic techniques used to confirm the structure of the synthesized hybrids. In addition, density functional theory (DFT) calculations were conducted to study the geometry optimization of some representative compounds, and their electronic transitions in DMSO were investigated by performing time-dependent DFT calculations. Additionally, a molecular docking study was carried out to investigate the possible interactions and binding mode of the newly synthesized compounds to the estrogen receptor (ER) binding site to estimate their anticancer activity against hormonally driven breast cancer.

Antiproliferative Activity and Ultrastructural Changes in Promastigote and Amastigote forms of Leishmania amazonensis Caused by Limonene-Acylthiosemicarbazide Hybrids.

Leishmaniasis is a tropical zoonotic disease. It is found in 98 countries, with an estimated 1.3 million people being affected annually. During the life cycle, the Leishmania parasite alternates between promastigote and amastigote forms. The first line treatment for leishmaniasis are the pentavalent antimonials, such as N-methylglucamine antimoniate (Glucantime®) and sodium stibogluconate (Pentostam®). These drugs are commonly related to be associated with dangerous side effects such as cardiotoxicity, nephrotoxicity, hepatotoxicity, and pancreatitis. Considering these aspects, this work aimed to obtain a new series of limonene-acylthiosemicarbazides hybrids as an alternative for the treatment of leishmaniasis. For this, promastigotes, axenic amastigotes, and intracellular amastigotes of Leishmania amazonensis were used in the antiproliferative assay; J774-A1 macrophages for the cytotoxicity assay; and electron microscopy techniques were performed to analyze the morphology and ultrastructure of parasites. ATZ-S-04 compound showed the best result in both tests. Its IC50 , in promastigotes, axenic amastigotes and intracellular amastigotes was 0.35±0.08 μM, 0.49±0.06 μM, and 15.90±2.88 μM, respectively. Cytotoxicity assay determined a CC50 of 16.10±1.76 μM for the same compound. By electron microscopy, it was observed that ATZ-S-04 affected mainly the Golgi complex, in addition to morphological changes in promastigote forms of L. amazonensis.

Design and Synthesis of Benzenesulfonamides Coupled with Piperidine, Morpholine, and N,N‐Dimethylethanamine Moieties as Apoptotic Inducers through VEGFR2 and Topoisomerase II Inhibition

AbstractNovel hybrid series of benzenesulfonamide coupled with piperidine, morpholine, and N,N‐dimethylethanamine moieties at sulfonyl group were designed through pharmacophore hybridization, synthesized, and evaluated for cancer treatment. Benzenesulfonamide‐based derivatives had been synthesized, structurally elucidated, and biologically evaluated as potent VEGFR2 kinase and topoisomerase II inhibitors with cytotoxicity against MCF‐7 and HepG2 cells. Interestingly, the most cytotoxic compound against MCF‐7 and HepG2 cells exhibited promising IC50 values of 0.08 and 0.186 μM, respectively, compared to Doxorubicin as the reference drug with IC50 values of 7.67 and 8.28 μM. It exhibited promising dual enzyme inhibition VEGFR2 and Topoisomerase II with IC50 values of 13.24 nM and 8.3 μM compared to Sorafenib and Doxorubicin as standard drugs. It significantly stimulated total apoptotic breast cancer cell death by 55.25‐fold (34.26 % compared to 0.62 for the control), arresting the cell cycle at S‐phase, which affected the apoptosis‐mediated genes through upregulating P53, Bax, caspases 3, 8, and 9 and downregulating the anti‐apoptotic gene Bcl‐2. A molecular docking study was conducted to confirm the binding affinity of the designed compounds towards VEGFR2 and Topoisomerase II proteins with good binding energy and interactive modes as their co‐crystallized ligands.