Benzylidene Barbituric Acid Derivatives Shown Anticonvulsant Activity on Pentylenetetrazole-Induced Seizures in Mice: Involvement of Nitric Oxide Pathway

ABSTRACT Background: Barbituric acid derivatives have long been used as central nervous system (CNS) suppressants, such as sedatives, hypnotics and anticonvulsants. In addition, previous studies have implicated the involvement of nitric oxide (NO) in the anticonvulsive effects of barbiturates in CNS. Therefore, the purpose of this study was to figure out the effects of a novel class of barbituric acid derivatives on pentylenetetrazole (PTZ)-induced seizures in male mice. Methods: Thirteen synthesized barbituric acid derivatives (a-m) and phenobarbital were administered intraperitoneally (i.p.) 30 min before induction of seizures by PTZ administration. The mechanisms of PTZ-induced seizures in the mice was evaluated using a non-selective nitric oxide synthase (NOS) inhibitor, selective inducible NOS (iNOS) inhibitor, a selective neuronal NOS (nNOS) inhibitor, and NO substrate. Results: Administration of most of the above mentioned derivatives significantly increased the seizures threshold (P<0.001). The most potent derivative (compound a), was chosen in order to investigate the mechanism of action involving in anticonvulsant activity. Administration of a non-selective NOS inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) and a selective nNOS inhibitor, 7-nitroindazole (7-NI) reversed anticonvulsant activity of compound a. However, injection of the nitric oxide precursor, L-arginine (L-Arg) and a selective iNOS inhibitor, aminoguanidine (AG), did not change anticonvulsant activity of the mentioned compound. Conclusion: These results indicated that the NO system, specifically nNOS may contribute to the anticonvulsant activity of benzylidene barbituric acid derivative a. Therefore, this compound is a good candidate in order to designing new anticonvulsant medication

Breast cancer cells imaging by targeting methionine transporters with gadolinium-based nanoprobe

Purpose: Early cancer diagnosis using MRI imaging is of high global interest as a non-invasive and powerful modality. In this study, methionine was conjugated on gadolinium-based mesoporous silica nanospheres to evaluate intra-cellular uptake and its accumulation in human breast cancer cells. Procedures: The contrast agent was synthesized and characterized using different techniques including N2 physisorption, thermal gravimetric analysis, dynamic light scattering, and inductively coupled plasma atomic emission spectroscopy (ICP-AES). The intra-cellular uptake of Gd3+ was measured by ICP-AES, fluorescent microscopy, and flow cytometry. Finally, cellular and tumor MR imaging were performed to determine in vitro and in vivo relaxometry. Results: According to the results, the contrast agents accumulated in tumor cells both in vitro and in vivo. There was no significant cellular toxicity on either normal or cancer cells along with strong intense signal on T1 compared to the unlabeled cells. Conclusions: The results showed that the novel contrast agent could become a useful tool in early detection of cancer. © 2014 World Molecular Imaging Society

Use of translation in the writings of International students learning English in Malaysia / Soheila Mahernia

There are increasing numbers of international students coming to Malaysia every year. One of the problems they face while they are learning English in ESL classrooms is to know whether it is beneficial or not for them to use their native language and translation as a tool for learning the second language. Second language researchers have also currently started to re-evaluate the role of translation and first language (L1) in ESL classrooms. This research was based primarily on an examination of direct and indirect (translated) essay writing in English by 25 college students from different Russian speaking countries having pre advanced and advanced level of English proficiency. The intension of this research is to investigate the quality of students’ writing with and without the use of translation by comparing and analysing their written output linguistically. The main research question in this study is: “How does translation help international students to improve their ESL essay writing?” For the purpose of triangulation, two questionnaires were used, one for the participants and another one for their instructors regarding their beliefs about the use of translation in ESL writing in order to answer the second research question: “What do the students’ think about the use of translation and mother tongue or L1 considering it to be a tool for ESL learning?” and the third research question : “What do the students’ instructors think about the use of translation and L1 in ESL classrooms?” An oral interview was also conducted to find out about the students’ beliefs regarding the use of translation in second language learning. The interview was recorded and transcribed accordingly. The results show that pre advanced (60%) students benefited more from translation than the advanced students. In the case of the advanced students’ writing there was no significant amount of change in their two writing products. The findings also show that iv majority of the participants (14), believed that with the use of translation they could write English compositions much better. Considering their instructors’ beliefs, it was observed by the reactions of their two teachers belonging to two different generations that nowadays some teachers of the new generation have started to realize the importance of using the L1 in second language learning. On the other hand, the older generation of ESL teachers regard the use of the L1 and translation in the classrooms as a taboo. The conclusions reached were that both pre advanced and advanced students in their translated writings had traces of Russian dominance according to the Russian translators assisting the researcher in the analysis of the writings. Hence, it is beneficial for the students that their instructors in ESL classrooms provide them suggestions on how the systematic use of translation can serve them. They should be guided to organize their ideas and provide information in a lexically and grammatically acceptable and appropriate way. In fact the findings suggest that there should be a focus on how these students select appropriate vocabulary both for their direct and indirect writing as well as learning to prevent their L1 from dominating their L2 lexis and syntax. Keywords: translation, mother tongue, first language (L1), student beliefs, language analysis, English as a Second Language (ESL), writing

Pantoprazole Derivatives: Synthesis, Urease Inhibition Assay and In Silico Molecular Modeling Studies

A number of pantoprazole derivatives were synthesized and screened for their urease inhibitory properties. Some of them showed potent inhibitions against jack bean urease. All compounds showed varying degree of IC50 in the range of 25.85 to 181 μMol as compared to standard acetohydroxamic acid (AHA) (100±2.02 μMol). Derivatives bearing 5-aryl-1,3,4-oxadiazole ring substitutions (aryl= pyrazyl, pyridyl and phenyl) were found to be more potent inhibitors than AHA and pantoprazole. The most promising compound, 2-((3,4-dimethoxypyridin-2-yl)methylthio)-5-(pyrazin-2-yl)-1,3,4-oxadiazole 12, with IC50 value of 25.85±1.21 showed remarkable urease inhibition activity. In silico molecular modeling investigation performed to rationalize the possible binding interaction and ADME properties of compounds over the active site of urease enzyme. The induced fit docking study showed that compound 12 interacted with conserved residues His593 and Arg609 located at the mouth of the urease active site flap and are essential for enzyme catalytic activity. These target compounds could be further studied as a lead skeleton for discovery of novel urease inhibitors. © 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinhei

Structure-based pharmacophore design and virtual screening for novel potential inhibitors of epidermal growth factor receptor as an approach to breast cancer chemotherapy

Cancer cells are described with features of uncontrolled growth, invasion and metastasis. The epidermal growth factor receptor subfamily of tyrosine kinases (EGFR-TK) plays a crucial regulatory role in the control of cellular proliferation and progression of various cancers. Therefore, its inhibition might lead to the discovery of a new generation of anticancer drugs. In the present study, structure-based pharmacophore modeling, molecular docking and molecular dynamics simulations were applied to identify potential hits, which exhibited good inhibition on the proliferation of MCF-7 breast cancer cell line and favorable binding interactions on EGFR-TK. Selected compounds were examined for their anticancer activity against the Michigan Cancer Foundation-7 (MCF-7) breast cancer cell line which overexpresses EGFR using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) tetrazolium reduction assay. Compounds 1 and 2, with an isoindoline-1-one core, induced significant inhibition of breast cancer cells proliferation with IC50 values 327 and 370 nM, respectively. © 2017, Springer International Publishing AG, part of Springer Nature