Exploiting new strategies in combating head and neck carcinoma: A comprehensive review on phytochemical approaches passing through PI3K/Akt/mTOR signaling pathway.

Recently, malignant neoplasms have growingly caused human morbidity and mortality. Head and neck cancer (HNC) constitutes a substantial group of malignancies occurring in various anatomical regions of the head and neck, including lips, mouth, throat, larynx, nose, sinuses, oropharynx, hypopharynx, nasopharynx, and salivary glands. The present study addresses the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway as a possible therapeutic target in cancer therapy. Finding new multitargeting agents capable of modulating PI3K/Akt/mTOR and cross-linked mediators could be viewed as an effective strategy in combating HNC. Recent studies have introduced phytochemicals as multitargeting agents and rich sources for finding and developing new therapeutic agents. Phytochemicals have exhibited immense anticancer effects, including targeting different stages of HNC through the modulation of several signaling pathways. Moreover, phenolic/polyphenolic compounds, alkaloids, terpenes/terpenoids, and other secondary metabolites have demonstrated promising anticancer activities because of their diverse pharmacological and biological properties like antiproliferative, antineoplastic, antioxidant, and anti-inflammatory activities. The current review is mainly focused on new therapeutic strategies for HNC passing through the PI3K/Akt/mTOR pathway as new strategies in combating HNC.

Protective effect of a hydromethanolic extract from Fraxinus excelsior L. bark against a rat model of aluminum chloride-induced Alzheimer's disease: Relevance to its anti-inflammatory and antioxidant effects.

ETHNOPHARMACOLOGICAL RELEVANCE: Fraxinus excelsior L. (FE), commonly known as the ash, belongs to the Oleaceae family and has shown several pharmacological and biological properties, such as antioxidant, immunomodulatory, neuroprotective, and anti-inflammatory effects. It has also attracted the most attention toward neuroinflammation. Moreover, FE bark and leaves have been used to treat neurological disorders, aging, neuropathic pain, urinary complaints, and articular pain in traditional and ethnomedicine. Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder resulting from the involvement of amyloid-beta, metal-induced oxidative stress, and neuroinflammation. AIM OF THE STUDY: The objective of the current study was to assess the neuroprotective effects of hydromethanolic extract from FE bark in an AlCl3-induced rat model of AD. MATERIALS AND METHODS: The maceration process was utilized to prepare the hydromethanolic extract of FE bark, and characterized by LC-MS/MS. To assess the anti-AD effects of the FE extract, rats were categorized into five different groups, AlCl3; normal control; FE-treated groups at 50, 100, and 200 mg/kg. Passive avoidance learning test, Y-maze, open field, and elevated plus maze behavioral tests were evaluated on days 7 and 14 to analyze the cognitive impairments. Zymography analysis, biochemical tests, and histopathological changes were also followed in different groups. RESULTS: LC-MS/MS analysis indicated the presence of coumarins, including isofraxidin7-O-diglucoside in the methanolic extract of FE as a new isofraxidin derivative in this genus. FE significantly improved memory and cognitive function, maintained weight, prevented neuronal damages, and preserved the hippocampus's histological features, as demonstrated by behavioral tests and histopathological analysis. FE increased anti-inflammatory MMP-2 activity, whereas it decreased that of inflammatory MMP-9. Moreover, FE increased plasma antioxidant capacity by enhancing CAT and GSH while decreasing nitrite levels in the serum of treated groups. In comparison between the treated groups, the rats that received high doses of the FE extract (200 mg/kg) showed the highest therapeutic effect. CONCLUSION: FE rich in coumarins could be an effective anti-AD adjunct agent, passing through antioxidant and anti-inflammatory pathways. These results encourage further studies for the development of this extract as a promising agent in preventing, managing, or treating AD and related diseases.

Inhibiting Angiogenesis by Anti-Cancer Saponins: From Phytochemistry to Cellular Signaling Pathways.

Saponins are one of the broadest classes of high-molecular-weight natural compounds, consisting mainly of a non-polar moiety with 27 to 30 carbons and a polar moiety containing sugars attached to the sapogenin structure. Saponins are found in more than 100 plant families as well as found in marine organisms. Saponins have several therapeutic effects, including their administration in the treatment of various cancers. These compounds also reveal noteworthy anti-angiogenesis effects as one of the critical strategies for inhibiting cancer growth and metastasis. In this study, a comprehensive review is performed on electronic databases, including PubMed, Scopus, ScienceDirect, and ProQuest. Accordingly, the structural characteristics of triterpenoid/steroid saponins and their anti-cancer effects were highlighted, focusing on their anti-angiogenic effects and related mechanisms. Consequently, the anti-angiogenic effects of saponins, inhibiting the expression of genes related to vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1-α (HIF-1α) are two main anti-angiogenic mechanisms of triterpenoid and steroidal saponins. The inhibition of inflammatory signaling pathways that stimulate angiogenesis, such as pro-inflammatory cytokines, mitogen-activated protein kinase (MAPKs), and phosphoinositide 3-kinases/protein kinase B (PI3K/Akt), are other anti-angiogenic mechanisms of saponins. Furthermore, the anti-angiogenic and anti-cancer activity of saponins was closely related to the binding site of the sugar moiety, the type and number of their monosaccharide units, as well as the presence of some functional groups in their aglycone structure. Therefore, saponins are suitable candidates for cancer treatment by inhibiting angiogenesis, for which extensive pre-clinical and comprehensive clinical trial studies are recommended.

Anti-nociceptive and anti-inflammatory activities of the essential oil isolated from Cupressus arizonica Greene fruits.

BACKGROUND: Cupressus arizonica Greene is a coniferous tree with great importance in fragrance and pharmaceutical industries. Essential oils from C. arizonica (EC) have shown potential antioxidant, and anti-microbial activities. This study aimed at investigating the anti-nociceptive and anti-inflammatory effects/mechanisms of EC. METHODS: The EC was evaluated for anti-nociceptive and anti-inflammatory activities on male Wistar rats using a formalin test and carrageenan-induced paw edema, respectively. Also, we pre-treated some of the animals with naloxone and flumazenil in the formalin test to find out the possible contributions of opioid and benzodiazepine receptors to EC anti-nociceptive effects. Finally, gas chromatography/mass spectrometry (GC/MS) analysis was used to identify the EC's constituents. RESULTS: EC in intraperitoneal doses of 0.5 and 1 g/kg significantly decrease the nociceptive responses in both early and late phases of the formalin test. From a mechanistic point of view, flumazenil administration 20 minutes before the most effective dose of EC (1 g/kg) showed a meaningful reduction in the associated antinociceptive responses during the early and late phases of the formalin test. Naloxone also reduced the anti-nociceptive role of EC in the late phase. Furthermore, EC at the doses of 1, 0.5, and 0.25 g/kg significantly reduced paw edema from 0.5 hours after carrageenan injection to 4 hours. GC/MS analysis showed that isolated EC is a monoterpene-rich oil with the major presence of α-pinene (71.92%), myrcene (6.37%), δ-3-carene (4.68%), ß-pinene (3.71%), and limonene (3.34%). CONCLUSIONS: EC showed potent anti-nociceptive and anti-inflammatory activities with the relative involvement of opioid and benzodiazepine receptors.

The effects of co-administration of artichoke leaf extract supplementation with metformin and vitamin E in patients with nonalcoholic fatty liver disease: A randomized clinical trial.

Medicinal plants are widely used as a complementary therapy to treat complex diseases, such as nonalcoholic fatty liver disease (NAFLD). Therefore, this study was done to investigate the effect of co-administration of artichoke leaf extract supplement (ALES) with conventional medicines on patients with NAFLD. The clinical trial was based on patients randomly divided into three groups involving metformin-vitamin E (ME), metformin-ALES (MA), and vitamin E-ALES (EA). The effectiveness of treatment in the treated groups was evaluated using liver ultrasonography and biochemical markers. After 12 weeks of treatment, the results showed that the rate of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) was significantly reduced within all the study groups (p < .05). Liver ultrasonographic findings revealed that the rate of fat accumulation in liver of patients was decreased significantly within all the study groups and it was increased in the subjects with grade 0 fatty liver (without fat accumulation) in the MA and EA groups by 23.3 and 17.2%, respectively. In summary, the results of the present study showed that the concomitant use of ALES with metformin and vitamin E can have beneficial effects on amelioration of complications in patients with NAFLD. However, larger-scale clinical trial studies are required in this regard.

Targeting miRNA by Natural Products: A Novel Therapeutic Approach for Nonalcoholic Fatty Liver.

The increasing prevalence of nonalcoholic fatty liver disease (NAFLD) as multifactorial chronic liver disease and the lack of a specific treatment have begun a new era in its treatment using gene expression changes and microRNAs. This study aimed to investigate the potential therapeutic effects of natural compounds in NAFLD by regulating miRNA expression. MicroRNAs play essential roles in regulating the cell's biological processes, such as apoptosis, migration, lipid metabolism, insulin resistance, and adipocyte differentiation, by controlling the posttranscriptional gene expression level. The impact of current NAFLD pharmacological management, including drug and biological therapies, is uncertain. In this context, various dietary fruits or medicinal herbal sources have received worldwide attention versus NAFLD development. Natural ingredients such as berberine, lychee pulp, grape seed, and rosemary possess protective and therapeutic effects against NAFLD by modifying the gene's expression and noncoding RNAs, especially miRNAs.

Natural products attenuate PI3K/Akt/mTOR signaling pathway: A promising strategy in regulating neurodegeneration.

BACKGROUND: As common, progressive, and chronic causes of disability and death, neurodegenerative diseases (NDDs) significantly threaten human health, while no effective treatment is available. Given the engagement of multiple dysregulated pathways in neurodegeneration, there is an imperative need to target the axis and provide effective/multi-target agents to tackle neurodegeneration. Recent studies have revealed the role of phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) in some diseases and natural products with therapeutic potentials. PURPOSE: This is the first systematic and comprehensive review on the role of plant-derived secondary metabolites in managing and/or treating various neuronal disorders via the PI3K/Akt/mTOR signaling pathway. STUDY DESIGN AND METHODS: A systematic and comprehensive review was done based on the PubMed, Scopus, Web of Science, and Cochrane electronic databases. Two independent investigators followed the PRISMA guidelines and included papers on PI3K/Akt/mTOR and interconnected pathways/mediators targeted by phytochemicals in NDDs. RESULTS: Natural products are multi-target agents with diverse pharmacological and biological activities and rich sources for discovering and developing novel therapeutic agents. Accordingly, recent studies have shown increasing phytochemicals in combating Alzheimer's disease, aging, Parkinson's disease, brain/spinal cord damages, depression, and other neuronal-associated dysfunctions. Amongst the emerging targets in neurodegeneration, PI3K/Akt/mTOR is of great importance. Therefore, attenuation of these mediators would be a great step towards neuroprotection in such NDDs. CONCLUSION: The application of plant-derived secondary metabolites in managing and/or treating various neuronal disorders through the PI3K/Akt/mTOR signaling pathway is a promising strategy towards neuroprotection.

Alkaloids as Potential Phytochemicals against SARS-CoV-2: Approaches to the Associated Pivotal Mechanisms.

Since its inception, the coronavirus disease 2019 (COVID-19) pandemic has infected millions of people around the world. Therefore, it is necessary to find effective treatments against Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), as it is the viral source of COVID-19. Alkaloids are one of the most widespread plant-derived natural compounds with prominent antiviral effects. Accordingly, these phytochemicals have been promising candidates towards discovering effective treatments for COVID-19. Alkaloids have shown potential anti-SARS-CoV activities via inhibiting pathogenesis-associated targets of the Coronaviridae family that are required for the virus life cycle. In the current study, the chemistry, plant sources, and antiviral effects of alkaloids, as well as their anti-SARS-CoV-2 effect with related mechanisms, are reviewed towards discovering an effective treatment against COVID-19.

Rapid and sensitive UHPLC-DAD method for simultaneous determination of sofosbuvir and ledipasvir in human serum.

Today, the direct-acting antiviral agents (DAAs) such as sofosbuvir (SOF) and ledipasvir (LED) are widely used to treat the hepatitis virus infection. The aim of this study was to develop a rapid, simple and valid method for simultaneous determination of SOF and LED in human plasma for bioavailability and pharmacokinetic studies. Chromatographic analysis was performed on the C18 column (Blue Orchid, 1.8 µm, 50 × 2 mm) using 0.1 % formic acid in water (pH 2.6) and acetonitrile (60:40; v/v) as mobile phase at a flow rate of 0.5 mL/min. The UV detector was set at 328 nm and 260 nm for analysis of SOF and LED, respectively. To 400 µL of plasma, 100 µL of clonazepam as the internal standard (I.S, 7 µg/mL) was added and the mixture subjected to liquid-liquid extraction using 1000 µL diethyl ether. The calibration curves were linear with coefficients of variation less than 8% for all analyses. The limit of quantification (LOQ) was 20 and 5 ng/mL for SOF and LED, respectively. The results of inter-day and intra-day precision showed good reproducibility and the total analysis time was 1.2 min. This method successfully applied for determination SOF and LED in four healthy volunteers.

Isofraxidin: Synthesis, Biosynthesis, Isolation, Pharmacokinetic and Pharmacological Properties.

Isofraxidin (7-hydroxy-6, 8-dimethoxy coumarin) (IF) is a hydroxy coumarin with several biological and pharmacological activities. The plant kingdom is of the most prominent sources of IF, which, among them, Eleutherococcus and Fraxinus are the well-known genera in which IF could be isolated/extracted from their species. Considering the complex pathophysiological mechanisms behind some diseases (e.g., cancer, neurodegenerative diseases, and heart diseases), introducing IF as a potent multi-target agent, which possesses several herbal sources and the multiple methods for isolation/purification/synthesis, along with the unique pharmacokinetic profile and low levels of side effects, could be of great importance. Accordingly, a comprehensive review was done without time limitations until February 2020. IF extraction methods include microwave, mechanochemical, and ultrasound, along with other conventional methods in the presence of semi-polar solvents such as ethyl acetate (EtOAc). In addition to the isolation methods, related synthesis protocols of IF is also of great importance. From the synthesis point of view, benzaldehyde derivatives are widely used as precursors for IF synthesis. Along with the methods of isolation and biosynthesis, IF pharmacokinetic studies showed hopeful in vivo results of its rapid absorption after oral uses, leading to different pharmacological effects. In this regard, IF targets varieties of inflammatory mediators including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), tumor necrosis factor-α (TNF-α), and matrix metalloproteinases (MMPs). thereby indicating anticancer, cardioprotective, and neuroprotective effects. This is the first review on the synthesis, biosynthesis, isolation, and pharmacokinetic and pharmacological properties of IF in combating different diseases.

Targeting Neurological Manifestations of Coronaviruses by Candidate Phytochemicals: A Mechanistic Approach.

The novel coronavirus 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made a wide range of manifestations. In this regard, growing evidence is focusing on COVID-19 neurological associations; however, there is a lack of established pathophysiological mechanisms and related treatments. Accordingly, a comprehensive review was conducted, using electronic databases, including PubMed, Scopus, Web of Science, and Cochrane, along with the author's expertize in COVID-19 associated neuronal signaling pathways. Besides, potential phytochemicals have been provided against neurological signs of COVID-19. Considering a high homology among SARS-CoV, Middle East Respiratory Syndrome and SARS-CoV-2, revealing their precise pathophysiological mechanisms seems to pave the road for the treatment of COVID-19 neural manifestations. There is a complex pathophysiological mechanism behind central manifestations of COVID-19, including pain, hypo/anosmia, delirium, impaired consciousness, pyramidal signs, and ischemic stroke. Among those dysregulated neuronal mechanisms, neuroinflammation, angiotensin-converting enzyme 2 (ACE2)/spike proteins, RNA-dependent RNA polymerase and protease are of special attention. So, employing multi-target therapeutic agents with considerable safety and efficacy seems to show a bright future in fighting COVID-19 neurological manifestations. Nowadays, natural secondary metabolites are highlighted as potential multi-target phytochemicals in combating several complications of COVID-19. In this review, central pathophysiological mechanisms and therapeutic targets of SARS-CoV-2 has been provided. Besides, in terms of pharmacological mechanisms, phytochemicals have been introduced as potential multi-target agents in combating COVID-19 central nervous system complications.

Phytochemicals: Potential Therapeutic Interventions Against Coronavirus-Associated Lung Injury.

Since the outbreak of coronavirus disease 2019 (COVID-19) in December 2019, millions of people have been infected and died worldwide. However, no drug has been approved for the treatment of this disease and its complications, which urges the need for finding novel therapeutic agents to combat. Among the complications due to COVID-19, lung injury has attained special attention. Besides, phytochemicals have shown prominent anti-inflammatory effects and thus possess significant effects in reducing lung injury caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Also, the prevailing evidence reveales the antiviral effects of those phytochemicals, including anti-SARS-CoV activity, which could pave the road in providing suitable lead compounds in the treatment of COVID-19. In the present study, candidate phytochemicals and related mechanisms of action have been shown in the treatment/protection of lung injuries induced by various methods. In terms of pharmacological mechanism, phytochemicals have shown potential inhibitory effects on inflammatory and oxidative pathways/mediators, involved in the pathogenesis of lung injury during COVID-19 infection. Also, a brief overview of phytochemicals with anti-SARS-CoV-2 compounds has been presented.

Antiangiogenic Effects of Coumarins against Cancer: From Chemistry to Medicine.

Angiogenesis, the process of formation and recruitment of new blood vessels from pre-existing vessels, plays an important role in the development of cancer. Therefore, the use of antiangiogenic agents is one of the most critical strategies for the treatment of cancer. In addition, the complexity of cancer pathogenicity raises the need for multi-targeting agents. Coumarins are multi-targeting natural agents belonging to the class of benzopyrones. Coumarins have several biological and pharmacological effects, including antimicrobial, antioxidant, anti-inflammation, anticoagulant, anxiolytic, analgesic, and anticancer properties. Several reports have shown that the anticancer effect of coumarins and their derivatives are mediated through targeting angiogenesis by modulating the functions of vascular endothelial growth factor as well as vascular endothelial growth factor receptor 2, which are involved in cancer pathogenesis. In the present review, we focus on the antiangiogenic effects of coumarins and related structure-activity relationships with particular emphasis on cancer.

Application of unfolded principal component analysis-radial basis function neural network for determination of celecoxib in human serum by three-dimensional excitation-emission matrix fluorescence spectroscopy.

This study describes a simple and rapid approach of monitoring celecoxib (CLX). Unfolded principal component analysis-radial basis function neural network (UPCA-RBFNN) and excitation-emission spectra were combined to develop new model in the determination of CLX in human serum samples. Fluorescence landscapes with excitation wavelengths from 250 to 310nm and emission wavelengths in the range 280-450nm were obtained. The figures of merit for the developed model were evaluated. High performance liquid chromatography (HPLC) technique was also used as a standard method. Accuracy of the method was investigated by analysis of the serum samples spiked with various concentration of CLX and a recovery of 103.63% was obtained. The results indicated that the proposed method is an interesting alternative to the traditional techniques normally used for determining CLX such as HPLC.

Synthesis, and In-vitro Cytotoxicity Studies of a Series of Triazene Derivatives on Human Cancer Cell Lines.

Compounds containing triazene ring structure are cytotoxic agents and clinically used as antitumor alkylating agents. In this study, a series of triazene derivatives holding alkyl and aryl moieties were synthesized and proved to be potent cytotoxic agents in-vitro particularly against eight cancer cell lines (PC3, HT29, Hela, HL60, Jurkat, K562, MCF7, HepG2) and a non-cancerous cell line (HUVEC). The cytotoxic activity was assessed using two methods, LDH assay, and trypan blue exclusion. Some of the triazene derivatives showed cytotoxic activity more than temozolomide (TMZ) as the reference drug. The synthesized triazenes showed marked cytotoxicity effects on all eight cancer cell lines. Among the compounds synthesized, 1,3-bis(2-ethoxyphenyl)triazene C had unique efficacy and selectivity so that it had IC50 between 0.560-3.33 µM on cancer cell lines and 12.61 µM on normal cell line (HUVEC). 1-(4-nitrophenyl)-3-(2-hydroxyethyl)triazene E shows weaker effect on cancer cell lines than the other compounds having IC50 between 3-15.54 µM.

9-fluorenylmethyl chloroformate as a fluorescence-labeling reagent for derivatization of carboxylic acid moiety of sodium valproate using liquid chromatography/tandem mass spectrometry for binding characterization: a human pharmacokinetic study.

In High Performance Liquid Chromatographic (HPLC) determination of chemicals with acidic functions, different labeling agents are used to improve sensitivity of the assay. 9-Fluorenylmethyl chloroformate (FMOC-Cl), on the other hand, is a suitable labeling agent, which reacts with both primary and secondary amines and less readily with hydroxyl groups in alkaline conditions. However, the reagent has not been applied in labeling of chemicals with acidic function yet. In this study which is the first report on application of FMOC-Cl in derivatization and analysis of a drug with acidic function, valproic acid (VPA), one of a series of fatty carboxylic acids with anticonvulsant activity, was derivatized using the reagent and quantified in serum samples by HPLC with fluorescence detection. In addition, to document the reaction between the labeling agent and carboxylic acid moiety of the drug, we developed a liquid chromatography-tandem MS/MS (LC-MS/MS) method. Following liquid-liquid extraction, derivatization of the drug and an internal standard was achieved in alkaline medium. The elute was monitored by a fluorescence detector with respective excitation and emission wavelengths of 265 and 315 nm. The present method is more sensitive comparing with other published HPLC procedures for analysis of VPA. The assay is sensitive enough to measure drug levels obtained in human single dose studies with a limit of quantification of 0.01 µg/mL. Also the method is linear over the concentrations range of 0.01-32 µg/mL of VPA in human serum using 100 µL serum sample and 5 µL injection. The coefficient variation values of both inter and intra day analysis were less than 12% and the percentage error was less than 4%. The method performance was studied and the validated procedure applied in a randomized cross-over bioequivalence study of two different VPA preparations in 24 healthy volunteers.

Catecholthioether derivatives: preliminary study of in-vitro antimicrobial and antioxidant activities.

In this research, synthesis, antimicrobial and antioxidant activities of a series of catecholthioethers having benzoxazole and tetrazole moieties are described. Antimicrobial activity was evaluated by minimum inhibitory concentration (MIC) assay. The synthesized compounds were tested in vitro against three Gram-positive bacteria including Staphylococcus aureus (clinical isolated), Staphylococcus aureus ATCC 25922, Enterococcus faecium (clinical isolated), and two Gram-negative bacteria including Klebsiella pneumoniae (clinical isolated) and Pseudomonas aeruginosa 27853 and the yeast Candida albicans in comparison with control drugs. Microbiological results indicated that the synthesized compounds possessed a broad spectrum of activity against the tested microorganisms at MIC values between 4-256 µg/ml. This shows compounds having tetrazole moiety were the most active against Gram-negative strains, whereas compounds having benzoxazole moiety were more active against Gram-positive ones. Also both of them showed significant antifungal activity against Candida albicans and had lower activity than the compared control drugs (Sulfamethoxazole and Fluconazole). The antioxidant activity was assessed using two methods, including, 1,1-biphenyl-2-picrylhydrazyl (DPPH) radical scavenging, and reducing power assays. Some of the catecholthioether derivatives showed antioxidant activity more than Trolox and butylated hydroxyanisole (BHA) as reference antioxidants.

Application of one-step liquid chromatography-electrospray tandem MS/MS and collision-induced dissociation to quantification of ezetimibe and identification of its glucuronated metabolite in human serum: A pharmacokinetic study.

A new one-step liquid chromatography-electrospray tandem MS/MS method is described to quantify ezetimibe (EZM) a novel lipid lowering drug in human serum. Also using collision-induced dissociation (CID) of the analyte, identification and chromatographic separation of its major metabolite, ezetimibe glucuronide (EZM-G) is achieved in this study. A thawed serum aliquot of 100µL was deproteinated by addition of 500µL methanol containing omeprazole as internal standard (I.S.). Separation of the drug, its metabolite and the I.S. were achieved using acetonitrile-water (70:30, v/v) as mobile phase at flow rate of 0.5mL/min on a MZ PerfectSil target C18 column. Multiple reaction monitoring (MRM) mode of precursor-product ion transition (408.7→272.0 for EZM and 345→194.5 for the I.S.) was applied for detection and quantification of the drug while, EZM-G was chromatographically separated and identified using CID. The analytical method was linear over the concentration range of 1-32ng/mL of EZM in human serum with a limit of quantification of 1ng/mL. The coefficient variation values of both inter- and intra-day analysis were less than 8% whereas the percentage error was less than 3.7. The validated method was applied in a randomized cross-over bioequivalence study of two different EZM preparations in 24 healthy volunteers.

Synthesis, in vitro antibacterial and carbonic anhydrase II inhibitory activities of N-acylsulfonamides using silica sulfuric acid as an efficient catalyst under both solvent-free and heterogeneous conditions.

Silica sulfuric acid catalyzes efficiently the reaction of sulfonamides with both carboxylic acid anhydrides and chlorides under solvent-free and heterogeneous conditions. All the reactions were done at room temperature and the N-acylsulfonamides were obtained with high yields and purity via an easy work-up procedure. This method is attractive and is in a close agreement with green chemistry. These compounds were also investigated for antibacterial activity, including Gram-positive cocci and Gram-negative bacilli, and carbonic anhydrase II inhibitory activity.