Phthalimide analogs as probable 15-lipoxygenase-1 inhibitors: synthesis,biological evaluation and docking studies

Background

Recent studies have been explained the role of lipoxygenases (LOX) in the origin of cancer. Among the lipoxygenases, the 5-LOX, 12-LOX and 15-LOX are more important in the cause of neoplastic disorders. In the present investigation, a new series of anticancer agents with 1,3,4-thiadiazole and phthalimide substructures were synthesized and their in vitro cytotoxicity was evaluated by MTT assay. Moreover, enzyme inhibitory potency was also assessed by enzymatic protocol towards 15-LOX-1. Molecular docking was performed to explore in silico binding mode of the target compounds.

Results

Tested compounds showed a better cytotoxic activity against HT29 cell line (colorectal cancer) in comparison with other cell lines (PC3: prostate carcinoma; SKNMC: neuroblastoma). Unfortunately, all of the tested derivatives rendered lower inhibitory potency than quercetin towards 15-LOX-1. Four hydrogen bonds were detected in docking studies for compound 4d as the most potent derivative in enzymatic assay.

Conclusions

The biological results of reported compounds in this research were not so satisfactory. But, further structural modifications are necessary to improve the bioactivity of these derivatives.     

The safety assessment of saffron (Crocus sativus L.) on sympathovagal balance and heart rate variability; a comparison with amiodarone

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Can gray values derived from CT and cone beam CT estimate new bone formation? An in vivo study

Objectives

The main aim of this study was to investigate whether Hounsfield unit derived from computed tomography (HU/CT) and gray value derived from cone beam computed tomography (GV/CBCT) can predict the amount of new bone formation (NBF) in the defects after bone reconstruction surgeries.

Materials and methods

Thirty calvaria defects created in 5 rabbits and grafted with both radiolucent (RL, n = 15) and radiopaque (RO, n = 15) bone substitute materials were evaluated, 8 weeks postoperatively. The defects were scanned by multislice computed tomography (Somatom®, Siemens Healthineers, Erlangen, Germany) and CBCT (NewTom VG®, Qualitative Radiology, Verona, Italy). MSCT and CBCT scans were matched to select the exact region of interest (ROI, diameter = 5 mm and height = 1 mm). HU/CT and GV/CBCT of each ROI were obtained. Mean amount of NBF in whole of the defects was measured using serial histomorphometric assessment. We investigated the correlation between HU/CT and GV/CBCT, HU/CT and NBF, and GV/CBCT and NBF generally, and separately among the RL or RO grafted defects, by linear generalized estimating equation modeling. Receiver operation characteristic analysis was performed to check the accuracy of HU/CT and GV/CBCT in diagnosing more than 10% NBF in the samples.

Results

There were linear correlations between HU/CT and GV/CBCT, HU/CT and NBF, and GV/CBCT and NBF.

Conclusion

According to the results, both HU/CT and GV/CBCT can be considered as fairly good predictors for assessment of the amount of NBF following bone reconstruction surgeries.

     

Effects of cigarette smoking on morphological features of platelets in healthy men

Objectives:

To assess the effects of cigarette smoking on thrombocytopoiesis and some platelet morphological parameters in healthy male smokers.

Methods:

In this cross-sectional study, 542 consecutive healthy men (aged 20 to 88 years), referred to the laboratory of Fatemieh Hospital, Semnan, Iran, between November 2011 and November 2012 for checking up were enrolled. The subjects were divided into 2 groups of smokers (n=258 with frequency of 10 or more cigarette per day with more than 12 months duration of smoking) and non-smokers (n=284). The blood samples were extracted to examine values of platelet indices using an ABX Micros 60 cell counter.

Results:

Comparing platelet indices across smokers and non-smokers showed that the mean platelet count was statistically significantly higher in adult smokers than in nonsmokers (264.1 ± 81.2/µl versus 247.7 ± 83.9/µl, p=0.021), while the mean plateletcrit value was contrarily lower in the adult smokers (18.0 ± 12.0% versus 25.0 ± 10.0%, p<0.001). Other platelet indicators were not discrepant between the smokers and non-smokers.

Conclusion:

Cigarette smoking in healthy individuals results in significant and considerable effects on platelet morphological indices. The mean platelet count is significantly increased, and plateletcrit values are reduced, compared with non-smoking status.The International Agency for Research on Cancer (IARC) in its recent reports introduced cigarette smoking as one of the main carcinogenic agents because of thousands of chemical compounds that induce the generation of free radicals, reduce prostacyclin production leading to clot formation, as well as increase the production of fibrinogen and coagulative factor VII.1,2 Smoking has been also identified as a principal underlying etiology for the occurrence and progression of cardiovascular diseases, inflammatory disorders, and oxidative stress stimulation.3 Cigarette smoking’s crucial role in disrupting platelet activation and aggregation, as well as other coagulation processing components leading to thrombotic formations has been recently suggested.4,5 The pathophysiological effects of cigarette smoking on platelet activation have been recently investigated. Cigarette smoking can induce both acute and chronic potential effects on platelet function. Shortly after smoking, acute platelet potentiating can be occurred that may be resulted in chronic desensitization of the cell to activating agents over time.6 A study showed that acute smoking can change the platelet count and induce endothelial damage,7 other study did not lead to platelet aggregation stimulated by adenosine diphosphate (ADP), epinephrine, and collagen such effects.8 Although it was observed that inhalation of cigarette smoke can trigger platelet aggregation mediated by thrombin and ADP.9 Even, reduced platelet agreeability induced by aggregating processes was shown in smokers compared with non-smokers.10 With due attention to this matter which was mentioned above, and because there are few reports on the effect of smoking on thrombocytopoiesis, we assessed the effect of cigarette smoking on thrombocytopoiesis and some platelet morphological parameters in healthy male smokers.     

Decreased serum total T3 level in hepatitis B and C related cirrhosis by severity of liver damage

Objective. Thyroid hormones profile in patients with hepatic cirrhosis due to chronic HBV and HCV infections was evaluated in order to find any relationship between thyroid hormones and severity of liver damage. Material and methods. Patients with the diagnosis of hepatic cirrhosis due to hepatitis B or C were screened for thyroid function status. Child-Pugh and model for end-stage liver disease (MELD) scores were calculated. Considering each thyroid function test, patients were divided into two groups with lower than normal and normal range of thyroid hormones, separately for each (for TSH, normal and upper than nor- mal). The correlation between thyroid function tests and severity of liver disease was taken into account. Results. Number of patients with a T3 level lower than normal range (70-110 ng/dL) significantly increased along with Child-Pugh scores A, B and C. A negative correlation was found between Child-Pugh scores and total serum T3 level (r = -0.453, P < 0.001). Also a reverse correlation was observed between MELD score and T3 levels (r = -0.305, P = 0.14). Conclusion. In conclusion serum T3 concentration is a good index of hepatic function, decreasing by the severity of liver damage.     

Relation between usual daily walking time and metabolic syndrome

Background:

There are several studies about the positive relation between physical inactivity or low cardio respiratory fitness with development of metabolic syndrome (MS). In contrast, physical activity had favourable effects on all components of MS but the quantity and the frequency of physical activity necessary to produce this beneficial effect has not been defined as yet. The aim of this survey was to study the association of regular physical activity, measured by patient''s estimation of walking time per day, with MS.

Materials and Methods:

This cross-sectional study was conducted as a part of Isfahan Healthy Heart Program (IHHP). Persons who had no component of MS were considered as reference group. Demographic data were collected by questionnaire. Relation between walking time and MS was evaluated by using logistic regression adjusted by age, sex, socioeconomic status (SES), life style and food item.

Results:

The study populations consisted of 4151 persons. Lower physical activity was associated with higher prevalence of MS (P < 0.001). There was a negative relation between the usual daily walking time and MS. Adjusted odds ratio for age groups, sex, SES, life style and food items (fat and oil, sweet and sweet drink, rice and bread, fried food) revealed that MS decreases with increasing walking time (P < 0.05) [OR = 0.70 (0.52-0.94)].

Conclusion:

Total daily walking time is negatively associated with MS and increasing daily walking time is an effective way for preventing MS.     

Use of Pindex System in Fabrication of the Sectional Custom Tray

This article describes a new, precise, and simple method for making an impression with an individual tray for a patient with microstomia. In this method, a Pindex system on the handle of the tray was used for attaching two parts of the sectional tray.     

N-(5-(Trifluoromethyl)-1,3,4-Thiadiazol-2-Yl)Benzamide and Benzothioamide Derivatives Induce Apoptosis Via Caspase-Dependent Pathway

Pharmaceutical Chemistry Journal - New 1,3,4-thiadiazole-based compounds were designed, synthesized, and their anticancer effects were assessed by MTT assay against PC3 (prostate cancer), HT-29...