The functional and molecular roles of p75 neurotrophin receptor (p75NTR) in epilepsy.

Epilepsy is a chronic neurological disorder manifested by recurring unprovoked seizures resulting from an imbalance in the inhibitory and excitatory neurotransmitters in the brain. The process of epileptogenesis involves a complex interplay between the reduction of inhibitory gamma-aminobutyric acid (GABA) and the enhancement of excitatory glutamate. Pro-BDNF/p75NTR expression is augmented in both glial cells and neurons following epileptic seizures and status epileptics (SE). Over-expression of p75NTR is linked with the pathogenesis of epilepsy, and augmentation of pro-BDNF/p75NTR is implicated in the pathogenesis of epilepsy. However, the precise mechanistic function of p75NTR in epilepsy has not been completely elucidated. Therefore, this review aimed to revise the mechanistic pathway of p75NTR in epilepsy.

Roles of p75 neurotrophin receptor (p75NTR) in epilepsy: Epilepsy is a chronic neurological disorder manifested by recurring unprovoked seizures resulting from an imbalance in the inhibitory and excitatory neurotransmitters in the brain. The process of epileptogenesis involves a complex interplay between the reduction of inhibitory gamma-aminobutyric acid (GABA) and the enhancement of excitatory glutamate. Pro-BDNF/p75NTR expression is augmented in both glial cells and neurons following epileptic seizures and status epileptics (SE). Over-expression of p75NTR is linked with the pathogenesis of epilepsy, and augmentation of pro-BDNF/p75NTR is implicated in the pathogenesis of epilepsy. However, the precise mechanistic function of p75NTR in epilepsy has not been completely elucidated.

Evaluation of the camel milk amelioration, the oxidative stress, fertility and mutagenicity of male albino rats exposed to lead acetate, fipronil, and their mixture.

Lead is considered a common old chronic toxicant around the world due to expanded environmental pollution, it is likely an inevitable contaminant in food, dairy products, air etc. Also, fipronil is a wide-ranging effective N-phenyl pyrazole insecticide which used commonly in agriculture and public health insect control, but until now no adequate data are available on the oxidative stress, cytotoxicity, and mutagenic influence of fipronil and lead or their mixture subchronic exposure. Both xenobiotics (lead and fipronil) exert a harmful impact on reproduction, prompting the exploration of various foods for functional protection. The present study investigated the effects of camel milk treatments on reproductive problems caused by lead acetate with or without mixing with fipronil in male albino rats. Liver oxidative stress, testicular relative weight, sperm analysis, investigation of chromosomal aberration, and histopathological examination of testis were performed. The results showed that the oxidative stress was elevated in rats treated with fipronil, lead acetate, and their mixture, which were reduced through camel milk treatments. Sperm counts were decreased significantly in lead and/or fipronil exposure but significantly elevated with camel milk intoxicated treated. Sperm morphological abnormalities and chromosomal aberrations in intoxicated groups were reduced significantly in camel milk-treated animals relative to untreated intoxicated groups. Testicular histopathological results showed moderate common degeneration of seminiferous tubules in lead and/or fipronil-intoxicated rats which were ameliorated by camel milk treatments. Generally, it can be concluded that lead and fipronil together in a mixture resulted in or induced severe reproductive problems and oxidative stress over lead or fipronil alone. Camel milk treatment significantly decreased the harmful oxidative stress in reproductive as well as the mutagenicity disorder associated with lead and fipronil exposure in male albino rats.

Sleep disorders cause Parkinson's disease or the reverse is true: Good GABA good night.

BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative brain disease due to degeneration of dopaminergic neurons (DNs) presented with motor and non-motor symptoms. PD symptoms are developed in response to the disturbance of diverse neurotransmitters including γ-aminobutyric acid (GABA). GABA has a neuroprotective effect against PD neuropathology by protecting DNs in the substantia nigra pars compacta (SNpc). It has been shown that the degeneration of GABAergic neurons is linked with the degeneration of DNs and the progression of motor and non-motor PD symptoms. GABA neurotransmission is a necessary pathway for normal sleep patterns, thus deregulation of GABAergic neurotransmission in PD could be the potential cause of sleep disorders in PD. AIM: Sleep disorders affect GABA neurotransmission leading to memory and cognitive dysfunction in PD. For example, insomnia and short sleep duration are associated with a reduction of brain GABA levels. Moreover, PD-related disorders including rigidity and nocturia influence sleep patterns leading to fragmented sleep which may also affect PD neuropathology. However, the mechanistic role of GABA in PD neuropathology regarding motor and non-motor symptoms is not fully elucidated. Therefore, this narrative review aims to clarify the mechanistic role of GABA in PD neuropathology mainly in sleep disorders, and how good GABA improves PD. In addition, this review of published articles tries to elucidate how sleep disorders such as insomnia and REM sleep behavior disorder (RBD) affect PD neuropathology and severity. The present review has many limitations including the paucity of prospective studies and most findings are taken from observational and preclinical studies. GABA involvement in the pathogenesis of PD has been recently discussed by recent studies. Therefore, future prospective studies regarding the use of GABA agonists in the management of PD are suggested to observe their distinct effects on motor and non-motor symptoms. CONCLUSION: There is a bidirectional relationship between the pathogenesis of PD and sleep disorders which might be due to GABA deregulation.

Cereal sprout-based food products: Industrial application, novel extraction, consumer acceptance, antioxidant potential, sensory evaluation, and health perspective.

Cereal grains are a good source of macronutrients and micronutrients that are required for metabolic activity in the human body. Sprouts have been studied to enhance the nutrient profile. Moreover, secondary metabolites are examined as green food engineering technology that is used in the pharmaceutical, functional ingredients, nutraceutical, and cosmetic industries. The sprout-based food is commonly used to enhance the quality of products by softening the structure of the whole grain and increasing the phytochemicals (nutritional value and bioactive compounds). These sprouting grains can be added to a variety of products including snacks, bakery, beverage, and meat. Consuming whole grains has been shown to reduce the incidence and mortality of a variety of chronic and noncommunicable diseases. Sprouting grains have a diversity of biological functions, including antidiabetic, antioxidant, and anticancer properties. Cereal sprout-based products are more beneficial in reducing the risk of cardiovascular diseases and gastrointestinal tract diseases. The novel extraction techniques (microwave-existed extraction, pulse electric field, and enzyme-associated) are applied to maintain and ensure the efficiency, safety, and nutritional profile of sprout. Nutrient-dense sprouts have a low environmental impact and are widely accepted by consumers. This review explores for the first time and sheds light on the antioxidant potential, sensory evaluation, industrial applications, and health perspective of cereal sprout-based food products.

Clover microgreen incorporation in diet-controlled diabetes and counteracted aflatoxicosis of rats.

Diabetes mellitus is one of the chronic metabolic diseases whose control remains a challenge. Its increased incidence was mainly attributed to increased environmental contamination. Therefore, this study aims to investigate the effect of feeding clover microgreen (CM) on a diabetes model with or without aflatoxin exposure. Rats were distributed into 8 groups. G1 was a control group. G2 was fed CM. G3 was administered aflatoxin orally. G4 was fed clover and administered aflatoxin. G5 was diabetic rats. G6 was diabetic rats fed CM. G7 was diabetic rats administered aflatoxin. G8 was diabetic rats administered aflatoxin and fed CM. Phytochemical analysis of the CM showed that gardenin was the most common compound. The administration of aflatoxin aggravated diabetes. The groups fed CM showed a decreased glucose concentration compared to the unfed groups. Liver and kidney function parameters were improved by CM. The histopathological alteration of the pancreas, liver, and kidneys was relieved in CM-fed groups. The area % of insulin in islets of Langerhans was increased in CM-fed groups. Feeding CM also enhanced the oxidative stress biomarkers. In conclusion, CM improved all evaluated parameters in diabetic rats either exposed to aflatoxin or not compared to the control.

Assessment of hepatoprotective, nephroprotective efficacy, and antioxidative potential of Moringa oleifera leaf powder and ethanolic extract against PCOS-induced female albino mice (Mus Musculus).

Moringa oleifera is a medicinal plant that has anti-inflammatory, antihypertensive, antidiabetic, tissue-protective, and antioxidant activities. Here, we evaluated the protective effect of M. oleifera leaf powder (MoLP) and 70% ethanol M. oleifera leaf extract (MoLE) on mitigating polycystic ovary syndrome (PCOS)-induced liver and kidney dysfunction via regulating oxidative stress in female albino mice (Mus musculus). The efficacy of M. oleifera was compared with metformin (standard medicine used to treat infertility in women). PCOS was induced by intramuscular injection of testosterone enanthate at 1.0 mg/100 g BW for 35 days. PCOS-induced mice were treated with MoLP (250 and 500 mg/Kg), MoLE (250 and 500 mg/kg), and metformin (250 mg/kg) orally for 14 days. Renal function test (RFT), liver function test (LFT), and oxidative stress biomarker malondialdehyde (MDA) were quantified in serum at 0, 7, and 14 days of intervention. Mice treated with M. oleifera and metformin showed a significant decrease (p < .001) in alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphate (ALP), total bilirubin, urea, creatinine, and a significant increase (p < .001) in total protein, albumin, globulin, and albumin/globulin (A/G) ratio. Oxidative stress decreased significantly (p = .00) with respect to treatments, exposure days, and their interaction in metformin and all M. oleifera-treated groups. M. oleifera leaf powder and extract reduce oxidative stress and enhance nephron-hepatic activity in PCOS-induced female albino mice.

Nutritional, biochemical, and clinical applications of carob: A review.

Carob is botanically called as Ceratonia siliqua and belongs to the Legumes family. The fruit is derived from hermaphrodite trees and hard in shape. The carob contains high sugar contents in pulp, fat in seed and minerals like potassium, calcium, and phosphorus are present in pods. Polyphenols and antioxidants are abundant in leaves and pods. It can be used for enhancing human health due to its high nutritional profile. Carob gum is used in the pharmaceutical industry in the form of pomades, anti-celiac ingredients, pills, and dental paste. The clinical carob can aid as an anti-cancer, anti-reflux, anti-diabetic, anti-diarrheal, anti-hyperlipidemia, anti-bacterial, anti-microbial, and anti-fungal. Nowadays, carob seeds are being used as an alternative to cocoa powder in food items whereas the leaves, pods, and seeds of carob are also historically used as food for animal feed. However, these parts of carob are available in markets with reasonable prices. Carob production, though with a rising contribution, contributes to the local economy. In this sense, we can incorporate knowledge on the chemical properties and the biological effect of carob fruits on human health. In this study, the supportive and health-promoting impacts of carob are discussed along with the clinical testing obtained from natural constituents of carob. In addition, further studies can be performed to extract and separate polyphenols and antioxidant potential for the development of functional that play a valuable role in pharmaceutical and food sectors.

The effect of different aqueous solutions ratios of Ocimum basilicum utilized in AgNPs synthesis on the inhibition of bacterial growth.

This study examined the effect of varying concentrations of Ocimum basilicum aqueous extract, which was done via the green synthesis of Silver nanoparticles (AgNPs), on the identification of the most effective concentration for bacteria inhibitory activity. Different concentrations of the aqueous Ocimum basilicum extract (0.25, 0.50, 0.75 and 1.00 mM) were used as reducing and stabilizing agent to synthesize AgNPs by means of the reduction method. The crystal structure and morphology of the NPs were characterized UV-Vis spectra, X-ray diffraction (XRD) and scanning electron microscopy (SEM). The antibacterial efficacy of AgNPs was studied against E. coli ATCC 35218 using well diffusion, MIC, MBC, and time-kill curve. The dark yellow color of the Ocimum basilicum aqueous solution indicates the successful synthesis process of the AgNPs. UV-spectra of the AgNPs display a gradual increase of absorption in sequence with concentration increase of aqueous Ocimum basilicum extract solution from 0.25 to 1.00 mM. This, in turn, led to a shift in the wavelength from 488 to 497 nm, along with a change in the nanoparticle size from 52 to 8 nm. The tests also showed a high activity of the particles against bacteria (E. coli), ranging between 15.6 and 62.5 µg/ml. Based on AgNPs, it was confirmed that an aqueous Ocimum basilicum extract can be used as an effective, reducing and stabilizing agent for the synthesis of different sizes of AgNPs based on the solvent concentration. The AgNPs also proved to be effective in inhibiting and killing bacteria.

Click synthesis of pyrrolidine-based 1,2,3-triazole derivatives as antifungal agents causing cell cycle arrest and apoptosis in Candida auris.

The emergence of multidrug-resistant fungal pathogens such as Candida auris is one of the major reasons WHO has declared fungal infections as a public health threat. Multidrug resistance, high mortality rates, frequent misidentification, and involvement in hospital outbreaks of this fungus demand the development of novel therapeutic drugs. In this direction, we report the synthesis of novel pyrrolidine-based 1,2,3-triazole derivatives using Click Chemistry (CC) and evaluation of their antifungal susceptibility against C. auris following Clinical and Laboratory Standards Institute (CLSI) guidelines. The fungicidal activity of the most potent derivative (P6) was further quantitatively confirmed by the MUSE cell viability assay. For insight mechanisms, the effect of the most active derivative on cell cycle arrest was studied using MuseTM Cell Analyzer and apoptotic mode of cell death was determined by studying phosphatidylserine externalization and mitochondrial depolarization. In vitro susceptibility testing and viability assays showed that all the newly synthesized compounds have antifungal activity with P6 being the most potent derivative. Cell cycle analysis revealed that P6 arrested the cells in S-phase in a concentration dependent manner and the apoptotic mode of cell death was confirmed by the movement of cytochrome c from mitochondria to cytosol with membrane depolarization. The hemolytic assay confirmed the safe use of P6 for further in vivo studies.

Modulation of key antioxidant enzymes and cell cycle arrest as a possible antifungal mode of action of cinnamaldehyde based azole derivative.

Although Candida auris was only identified in the year 2009, it has rapidly spread in more than a dozen countries and is proving more deadly and notorious. In our previous studies, we reported on the tremendous antifungal potential of a series of cinnamaldehyde based azole derivatives against fluconazole susceptible and resistant clinical isolates of Candida albicans and identified a promising lead molecule (6f). In this study, the effect of this compound on the viability and physiology of cell death in C. auris was assessed. The impact of compound 6f on cell cycle, oxidative stress enzymes and transcriptional profile of genes encoding these oxidative stress enzymes was also analysed. The results confirmed that compound 6f possessed the minimum inhibitory concentration of 0.98 µg/mL and prevented the growth and caused death in yeast cells. Furthermore, the compound at subinhibitory and inhibitory concentrations blocked the cell cycle in C. auris at S phase and G2/M phase and inhibited expression as well as activity of antioxidant enzymes that resulted in production of reactive oxygen species. Altogether, compound 6f showed potential antifungal activity against a virulent strain of C. auris and was able to induce oxidative stress and arrested cell cycle in C. auris and therefore, it can be considered as a strong candidate for antifungal drug development against C. auris.

Quorum Sensing and Biofilm Disrupting Potential of Imidazole Derivatives in Chromobacterium violaceum Using Antimicrobial and Drug Discovery Approaches.

Population of drug-resistant bacteria have increased at an alarming rate in the past few decades. The major reason for increasing drug resistance is the lack of new antibiotics and limited drug targets. It has therefore been a vital task to develop new antibiotics with different drug targets. Two such targets are biofilm formation and quorum sensing. Quorum sensing is cell to cell communication used by bacteria that initiates many important survival processes and aids in establishing pathogenesis. Both biofilm and quorum sensing are inter-related processes and play a major role in physiological and pathogenesis processes. In this study, five novel imidazole derivatives (IMA-1-IMA-5) were synthesised and tested for their antibacterial and anti-quorum sensing activities against Chromobacterium violaceum using different in silico and in vitro techniques following the standard protocols. In silico results revealed that all compounds were able to effectively bind to and interact sufficiently with the target protein CviR. CviR is a protein to which autoinducers bind to initiate the quorum sensing process. In silico results also revealed that the compounds generated favourable structural dynamics implying that the compounds would be able to effectively bind to CviR and inhibit quorum sensing. Susceptibility results revealed that IMA-1 is the most active of all the derivatives against both planktonic cells and biofilms. Qualitative and quantitative evaluation of anti-quorum sensing activity at sub-inhibitory concentrations of these compounds also revealed high activity for IMA-1. Down-regulation of most of the quorum sensing genes when cells were treated with the test compounds affirmed the high anti-quorum sensing activities of these compounds. The results from this study are promising and urges on the use of anti-quorum sensing and biofilm disrupting molecules to combat multi-drug resistance problem.

Markovian analysis of unreliable multi-machine flexible manufacturing cell.

In this paper, a Markovian model is constructed to test a flexible manufacturing cell's (FMC) performance. The considered FMC includes a conveyer belt, robot, and n machines. The conveyer belt delivers the working part to the robot, and the robot picks it up and loads it onto the machines. The movement of a working part from one step to the next depends on the availability of the tool in the next step (i.e., conveyer belt, robot, and machine). Any machine is assumed to potentially fail during the processing time as a result of high loading stresses. First, a Markovian model is constructed for single-machine and double-machine FMCs. Then, a generalized FMC with an n-machine is constructed. The introduced model is illustrated with two numerical examples for both the single- and triple-machine. The Markov chain model can be used to estimate the FMC performance measures (i.e., overall utilization of machines and production rate). It is used to analyze the response of these measures under varying parameters (i.e., conveyor belt delivery rate, robot loading rate, processing rate of a machine, failure rate of a machine, and down machines' repairing rate). Moreover, an economic model based on the Markov chain model is introduced to analyze the FMC's net profit under these varying parameters.

Citral derivative activates cell cycle arrest and apoptosis signaling pathways in Candida albicans by generating oxidative stress.

For combating life-threatening infections caused by Candida albicans there is an urgent requirement of new antifungal agents with a targeted activity and low host cytotoxicity. Manipulating the mechanistic basis of cell death decision in yeast may provide an alternative approach for future antifungal therapeutics. Herein, the effect of an active citral derivative (Cd1) over the physiology of cell death in C. albicans was assessed. The viability of C. albicans SC5314 cells was determined by broth microdilution assay. The crucial morphological changes and apoptotic markers in Cd1-exposed yeast cells were analyzed. Subsequently the results confirmed that Cd1 arrested growth and caused death in yeast cells. Furthermore, this molecule inhibited antioxidant enzymes that resulted in production of reactive oxygen species. DNA fragmentation and condensation, phosphatidylserine exposure at the outer leaflet of cell membrane, mitochondrial disintegration as well as accumulation of cells at G2/M phase of the cell cycle were recorded. Altogether, this derivative induced apoptotic-type cell death in C. albicans SC5314.

Azole Based Acetohydrazide Derivatives of Cinnamaldehyde Target and Kill Candida albicans by Causing Cellular Apoptosis.

Opportunistic fungal pathogens including Candida albicans are responsible for the alarming rise in hospital acquired infections and millions of deaths worldwide. The current treatment modalities are not enough to handle this situation, and therefore, new treatment modalities and strategies are desperately needed. In this direction, we synthesized a series of azole based acetohydrazide derivatives of cinnamaldehyde and subjected it to antifungal activity evaluation. Preliminary antifungal activity evaluation revealed tremendous antifungal potential of some of the derivatives against fluconazole susceptible and resistant clinical isolates of Candida albicans. Although all the compounds in the series are structurally similar except for the presence of different substituents on the phenyl ring of the acetohydrazide pendent, they sharply differed in their activity profile. Further mechanism of action studies revealed that these compounds have an apoptotic effect on C. albicans confirmed via Annexin V-FITC staining and TUNEL assay.

Shelf life extension of wheat bread by alhydwan flour and Carboxymethylcellulose and improvement of their quality characteristics, dough rheological and microstructure.

Alhydwan, has been used in bakery products for many years in South of Yemen. Alhydwan primary function in bakery products is to inhibit moisture content during storage, leading to improved shelf life. However, as a fresh strategy to bread staling, no extensive study has been conducted to evaluate its potential. The present study therefore examined the alhydwan as a comparison with Carboxymethylcellulose (CMC) at 0.5% (w/w) level in dough rheology improvement, microstructure, quality parameters and delayed wheat bread staling. The CMC or alhydwan for farinograph characteristics comprising the dough's portrayed showed greater water absorption, while growth and stability time was significantly decreased. Staling of bread, the findings showed that in both alhydwan and CMC minimized crumb hardening frequency and enhanced freshness, quality and retention ability for moisture, making the bread softer and postponed staling. The microstructure of CMC or alhydwan supplemented formulation showed the distinguishable characteristics and constituents that could explain, to some degree, that the CMC and alhydwan had antistaling effect. The incorporation of alhydwan such as CMC into the formulation of bread could thus play a sustainable role in improving the quality of bread by having an extended shelf life.

Development of an ergonomic four-finger-push manual pipette design.

The purpose of this study was to develop a new pipette design in which the pipette is operated by four fingers, taking into account the anatomy and anthropometry of the hand. The proposed new pipette designs were compared with a traditional thumb-push pipette based on muscle activity, wrist posture, subjective discomfort ratings for upper extremities, and user preference. The results of the study revealed that the four-finger, ergonomic pipette design reduced muscle exertion (25% reduction for aspiration and 35% reduction for dispensing), awkward wrist posture (33% reduction in wrist flexion, radial and ulnar deviation), and perceived discomfort in the wrist, hand and lower arm. Furthermore, most participants (9 of 10) who used a pipette in their daily work preferred the new pipette designs to a traditional thumb-push pipette design. Thus, we expect that this study will contribute to the reduction of WMSDs risk factors and pain.

Synthesis and synergistic studies of isatin based mixed ligand complexes as potential antifungal therapeutic agents.

Metal based drugs are important class of chemotherapeutic agents that have the potential to circumvent drug resistance. Increasing drug resistance, treatment failures and limited treatment options necessitates the development of new therapeutic drugs with different mechanisms of action. Towards this direction, we synthesized a series of isatin based mixed ligand complexes of [Cu(dbm)LClH2O] (mlc1), [Co(dbm)LCl2]‒ (mlc2) and [Ni(dbm)LClH2O] (mlc3) and evaluated their antifungal activity alone and in combination with fluconazole (FLC) against seven different Candida albicans isolates. The insight mechanism of antifungal action was revealed by studying apoptosis via terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. The study revealed that all these compounds showed antifungal activity at varying concentrations with mlc3 as the most potent compound with minimum inhibitory concentration ranging from 0.5-8 µg/mL and minimum fungicidal concentration ranging from 4-16 µg/mL. Upon combination with FLC, most of the interactions were either synergistic (54 %) or additive (32 %) with no antagonistic combination against any of the tested isolate. The study on their mechanism of action revealed that these compounds show apoptotic effect on C. albicans at sub-inhibitory concentrations, suggesting that strategies to target this process may augment the current antifungal treatment modalities.

α-Amylase immobilization on amidoximated acrylic microfibres activated by cyanuric chloride.

Enzyme immobilization is one of the most important techniques for industrial applications. It makes the immobilized enzyme more stable and advantageous than the free form in different aspects. α-Amylase was immobilized on 4% cyanuric chloride-activated amidoximated acrylic fabric at pH 7.0 with (79%) maximum efficiency. A field emission scanning electron microscope and Fourier transform infrared were used to confirm the immobilization process. Even after being recycled 10 times, the immobilized enzyme lost just 28% of its initial activity. Owing to immobilization, the pH of the soluble α-amylase was shifted from 6.0 to 6.5. The immobilized α-amylases showed thermal stability at 60°C, and became more resistant to heavy metal ions. The k m values of the immobilized and soluble α-amylases were 9.6 and 3.8 mg starch ml-1, respectively. In conclusion, this method shows that the immobilized α-amylase proved to be more efficient than its soluble form, and hence could be used during saccharification of starch.

Synthesis, spectroscopic, single crystal diffraction and potential nonlinear optical properties of novel pyrazoline derivatives: Interplay of experimental and computational analyses.

Pyrazoline are widely being studied due to their potential applications in chemical field. Herein, five pyrazolines compounds were synthesized and characterized spectroscopically using nuclear magnetic resonance techniques (1H NMR &13C NMR) to determine the structures of molecules along-with UV-Visible and infrared (FT-IR) studies for additional spectroscopic support in characterization of entitle synthesized molecules. Unit cells, specific space groups, bond lengths, bond angles and hydrogen bonding interactions were determined by the x-ray diffraction studies. Further, computational study of compounds with B3LYP/6-311 + G(d,p) level were carried out to explore optimized geometry, spectroscopic data for FT-IR, frontier molecular orbitals (FMOs) and non-linear optical (NLO) parameters. While, UV-Vis spectral were performed by TD-DFT/B3LYP/6-311 + G(d,p) level. The experimental results of spectroscopic and single crystal studies were compared and found in good agreement with the computational. The global reactivity parameters have been calculated with the help of the energy of FMOs. The order for the total first and second order hyperpolarizabilities of 1-5 is found in the following orders: 1 > 4 > 3 > 5 > 2 and 1 > 4 > 5 > 2 > 3 respectively. Overall, greater NLO response than urea molecule prove that investigated molecules are excellent candidate for NLO applications.

Synergistic antifungal effect of cyclized chalcone derivatives and fluconazole against Candida albicans.

The occurrence of invasive fungal diseases, particularly in immunocompromised patients, is life-threatening and increases the economic burden. The rising problem of multi-drug resistance is becoming a major concern for clinicians. In addition, a repertoire of antifungal agents is far less in number than antibacterial drugs. To combat these problems, combination therapy has gained a lot of interest. We previously reported the synergistic interaction of some mono- and bis-dihydropyrimidinone and thione derivatives with fluconazole and amphotericin B for combination antifungal therapy. In this study we used the same approach and synthesized different azole and non-azole derivatives of mono-(M) and bis-(B) chalcones and evaluated their antifungal activity profile alone and in combination with the most commonly used antifungal drug - fluconazole (FLC) - against seven FLC susceptible and three FLC resistant clinically isolated Candida albicans strains. Based on the minimum inhibitory concentration results, the bis-derivatives showed lower MIC values compared to their mono-analogues. Both fractional inhibitory concentration index and isobologram results revealed mostly synergistic, additive or indifferent interactions between the tested compounds and FLC against different Candida isolates. None of the tested compounds showed any effect on energy dependent R6G efflux, revealing that they do not reverse the mechanism of drug efflux. However, surprisingly, these compounds profoundly decreased ergosterol biosynthesis and showed down regulation of ERG11 gene expression, which is the possible mechanism of reversal of azole drug resistance by these compounds. These results provide a platform for further research to develop pyrimidinone/thione ring containing compounds as promising new antifungal agents, which could be used in antifungal combination therapy.