Design, Synthesis and Biological Evaluation of New 5,5-Diarylhydantoin Derivatives as Selective Cyclooxygenase-2 Inhibitors

A new group of 5,5-diarylhydantoin derivatives bearing a methylsulfonyl COX-2 pharmacophore at the para position of the C-5 phenyl ring were designed and synthesized as selective COX-2 inhibitors. In vitro COX-1/COX-2 inhibition structure-activity relationships identified 5-[4-(methylsulfonyl)phenyl]-5-phenyl-hydantoin (4) as a highly potent and selective COX-2 inhibitor (COX-2 IC50 = 0.077 μM; selectivity index > 1298). It was more selective than the reference drug celecoxib (COX-2 IC50 = 0.060 μM; selectivity index = 405). A molecular modeling study where 4 was docked in the binding site of COX-2 indicated that the p-MeSO2 COX-2 pharmacophore group on the C-5 phenyl ring is oriented in the vicinity of the COX-2 secondary pocket. The results of this study showed that the type of substituent on the N-3 hydantoin ring substituent is important for COX-2 inhibitory activity

Optimization of Aflatoxin B1 Aptasensing

Combination of aptamers with DNAzymes attracted intense attention for development of DNA-based biosensors for detection of mycotoxins. In the present study a combination of aflatoxin B1 specific aptamer and HRP- (horseradish peroxidase-) mimicking DNAzyme was optimized for detecting aflatoxin B1. Detecting approach is based on the binding affinity of aflatoxin B1 to its specific aptamer and conversion of substrate to a detectable colorimetric signal by a linked DNAzyme. Compared to conventional methods for aflatoxin B1 detection, DNA-based assay has the advantages of low cost, long-term stability, and rapid, simple, and user-friendly steps

Application of the oxycodone templated molecular imprinted polymer in adsorption of the drug from human blood plasma as the real biological environment; a joint experimental and density functional theory study

In this project, we have synthesized and used a molecular imprinted polymer (MIP) for adsorption of oxycodone residue from the biological samples. Indeed, this study aims to develop a suitable method for determination of oxycodone drug residue in the human plasma using the common analysis methods. Therefore, the MIP was used for the solid phase extraction (MIP-SPE) approach in order to collect the oxycodone opioid and to concentrate it in the blood plasma samples. The extraction parameters such as adsorption time, pH, and the amount of sorbent in blood plasma were optimized and the capacity of loading amount (LA) for adsorbing it was determined. Moreover, a high performance liquid chromatography (HPLC)-UV detector method was validated and used for analyzing of the mentioned opioid extracted from plasma. The results showed that the limit of detection (LOD), and the limit of quantization (LOQ) for the developed MIP-SPE method were 1.24 ppb, and 3.76 ppb, respectively. Moreover, both of the MIP-, and non-imprinted polymers (NIP)-drug complexes were designed and were then optimized by the density functional theory (DFT) method. The results showed that the theoretical calculations supported the experimental data, confirming the favorability of adsorption of the drug by MIP compared to NIP

Evaluation of Cytotoxicity Effects of Chalcone Epoxide Analogues as a Selective COX-II Inhibitor in the Human Liver Carcinoma Cell Line

Objectives: Study of the mechanisms involved in cancer progression suggests that cyclooxygenase enzymes play an important role in the induction of inflammation, tumor formation, and metastasis of cancer cells. Thus, cyclooxygenase enzymes could be considered for cancer chemotherapy. Among these enzymes, cyclooxygenase 2 (COX-2) is associated with liver carcinogenesis. Various COX-2 inhibitors cause growth inhibition of human hepatocellular carcinoma cells, but many of them act in the COX-2 independent mechanism. Thus, the introduction of selective COX-2 inhibitors is necessary to achieve a clear result. The present study was aimed to determine the growth-inhibitory effects of new analogues of chalcone epoxide as selective COX-2 inhibitors on the human hepatocellular carcinoma (HepG2) cell line. Methods: Estimation of both cell growth and the amount of prostaglandin E2 (PGE2) production were used to study the effect of selective COX-2 inhibitors on the hepatocellular carcinoma cell. Cell growth determination has done by MTT assay in 24 h, 48 h and 72 h, and PGE2 production has estimated by using ELYSA kit in 48 h and 72 h. Results: The results showed growth inhibition of the HepG2 cell line in a concentration and time-dependent manner, as well as a reduction in the formation of PGE2 as a product of COX-2 activity. Among the compounds those analogues with methoxy and hydrogen group showed more inhibitory effect than others. Conclusion: The current in-vitro study indicates that the observed significant growth-inhibitory effect of chalcone-epoxide analogues on the HepG2 cell line may involve COX-dependent mechanisms and the PGE2 pathway parallel to the effect of celecoxib. It can be said that these analogues might be efficient compounds in chemotherapy of COX-2 dependent carcinoma specially preventing and treatment of hepatocellular carcinomas

Chlorpyrifos Toxicity in Mouse Cultured Cerebellar Granule Neurons at Different Stages of Development: Additive Effect on Glutamate-Induced Excitotoxicity

Objective: Chlorpyrifos (CPF) is a neurotoxic organophosphorus (OP) insecticide. Its mechanism of action includes oxidative stress, excitotoxicity, and inhibition of the acetylcholinesterase enzyme (AChE). The aim of the present study is to investigate CPF toxicity in mature and immature cerebellar granule neurons (CGNs), as well as its effect on glutamate induced excitotoxicity. Materials and Methods: This study was an in vitro experimental study performed on mice cultured CGNs. Immature and mature neurons were exposed to different concentrations of CPF (1-1000 μM) and glutamate (10-600 μM) for 48 hours after which we used the MTT assay to measure cytotoxicity. Immature neurons had exposure to CPF for 5 days in order to evaluate the cytotoxic effect on developing neurons. Mature neurons received sub-lethal concentrations of CPF (10, 100 μM) combined with different concentrations of glutamate. AChE activity and reactive oxygen species (ROS) generation were assessed after treatments. Results: Immature CGNs had increased sensitivity to CPF toxicity compared to mature neurons. We observed significantly greater ROS production in immature compared to mature neurons, however AChE activity was more inhibited in mature neurons. Although CPF toxicity was not well correlated with AChE inhibition, it correlated well with ROS production. Glutamate toxicity was potentiated by sub-lethal concentration of CPF, however glutamate induced ROS production was not affected. The results suggested that CPF potentiated glutamate toxicity by mechanisms other than oxidative stress. Conclusion: CPF toxicity differed in mature and immature neurons. Potentiated glutamate toxicity by CPF implied that CPF exposure might be a risk factor for neurodegenerative disease

Evaluation of noises in different government hospitals of Khorramabad in winter 2017

Background: One of the physical factors in the hospital environment is the sound. The sound can interfere with comfort and normal activities of patients. An annoying sound can prevent the proper staffing of the hospital in the direction of the patient's activities. The aim of this study was to measure noise pollution level in various parts of government hospitals in Khorramabad city.Materials and Methods: This study was a cross-sectional study. Sound at the hospital was measured at two times in the morning and in the evening. The sound was measured by digital sound level meter models CEL440. Collected Data with were analyzed using MS excel and SPSS 22 (ANOVA and T test).Results: The mean of sound equivalent level was obtained in Dialysis, Cardiac admission, Admission to men, internal admission of men, Admission to children, ICU, CCU, NICU of Shahid Rahimi Hospital. And the ICU section and Cardiac of Shahid Madani hospital. The highest and lowest sound level were in parts of NICU and CCU, respectively.Conclusion: The findings showed that there was a significant relationship (Pvalue<0.001) between the measured level of sound at the time and place of most parts. Sound level was higher in the morning than the evening. The measured sound was significantly relationship in the two hospital. Also, The measured sound was higher than the standards (35 dB), which seems to have to take control measures in this regard

Evaluation of noises in different government hospitals of Khorramabad in winter 2017

Background: One of the physical factors in the hospital environment is the sound. The sound can interfere with comfort and normal activities of patients. An annoying sound can prevent the proper staffing of the hospital in the direction of the patient's activities. The aim of this study was to measure noise pollution level in various parts of government hospitals in Khorramabad city.Materials and Methods: This study was a cross-sectional study. Sound at the hospital was measured at two times in the morning and in the evening. The sound was measured by digital sound level meter models CEL440. Collected Data with were analyzed using MS excel and SPSS 22 (ANOVA and T test).Results: The mean of sound equivalent level was obtained in Dialysis, Cardiac admission, Admission to men, internal admission of men, Admission to children, ICU, CCU, NICU of Shahid Rahimi Hospital. And the ICU section and Cardiac of Shahid Madani hospital. The highest and lowest sound level were in parts of NICU and CCU, respectively.Conclusion: The findings showed that there was a significant relationship (Pvalue<0.001) between the measured level of sound at the time and place of most parts. Sound level was higher in the morning than the evening. The measured sound was significantly relationship in the two hospital. Also, The measured sound was higher than the standards (35 dB), which seems to have to take control measures in this regard

Route exposure and adverse effects monitoring of Aflatoxin B1 in the workers of wet waste management, the role of body redox system modulation

Exposure to dust, containing different fungi metabolites such as aflatoxins is a risk factor for developing liver and kidney health abnormalities. Occupational evaluation of the aflatoxin's exposure-induced health abnormalities should include the monitoring of bioaerosols in the workplace and personal air, and applying of appropriate blood biomarkers to assess Aflatoxin B1 (AFB1) detrimental effects on a worker’s health. However, to the best of our knowledge, these appropriate methods, especially determining the associated-adverse effects on health, following exposure, haven't been well documented in the literature at the wet waste handling sites. In the current study, the AFB1 quantity in the area, personal, and settled dust in wet household waste handling samples and AFB1-Albumin levels in the serum of workers in comparison with the control group were determined using high-pressure liquid chromatography with a fluorescent detector (HPLC-FLD) methods. Moreover, the adverse effects of AFB1 on the liver and kidney biochemical profiles of the exposed workers and its relation to antioxidant capacity in the household wet waste sorting were recorded in a consolidated investigation. The results demonstrated that the average airborne dust concentration and its associated AFB1 content were significantly higher in wet waste management sections as compared to the control place, corresponding to the serum AFB1-Albumin levels of workers. Furthermore, AFB1-induced changes in the serum biochemicals evaluating liver and kidney function tests and antioxidant profiles of workers in wet waste handling sections were indicative of their function abnormalities. The results imply AFB1-induced adverse effects on the liver and kidney functions may be mediated through the body redox system modulation

The Effect of Rebadioside A on Attenuation of Oxidative Stress in Kidney of Mice under Acetaminophen Toxicity

Background: Acetaminophen (APAP) overdose causes renal and hepatic injury. It is also believed that oxidative stress has a pivotal role in APAP-induced renal injury. Therefore, protective effects of different antioxidants have been examined in APAP-induced renal and hepatic toxicity models. Stevia rebadiana is a plant with a high degree of natural antioxidant activity in its leaf extract. The aim of this study was to investigate the possible protective effects of rebadioside A; one of the main components of stevia extract, on APAP-induced oxidative stress in kidney of mice. Methods: Oxidative stress was induced in kidney of BALB/c mice by the intraperitoneal (i.p.) administration of a single dose of 300 mg/kg APAP. Some of these mice also received rebadioside A (700 mg/kg) (i.p.) 30 minutes after APAP injection. Two and six hours after APAP injection, all mice were sacrificed and malondialdehyde (MDA), glutathione (GSH), free APAP, and glutathione conjugated of APAP (APAP-GSH) were determined in the kidney tissue. Results: GSH depletion and MDA levels significantly (P<0.05) increased in mice treated with either APAP or APAP plus Rebadioside A, respectively in 2 and 6 hours intervals after APAP administration. Significantly (P<0.05) higher levels of free APAP and APAP-GSH levels detected in kidney of mice administrated with APAP plus rebadioside A compared to APAP treated ones. Conclusion: Rebadioside A may be a potential compound in alleviation of APAP-induced oxidative stress in kidney of mice after APAP overdoses