Journal of Pharmacy Research最新文献_第7页

Pharmacogenomics of drug resistance in Breast Cancer Resistance Protein (BCRP) and its mutated variants 乳腺癌耐药蛋白(BCRP)及其突变体耐药的药物基因组学研究

Journal of Pharmacy Research

Pub Date : 2013-07-01 DOI: 10.1016/j.jopr.2013.06.020

Sugunakar Vuree , Nageswara Rao Dunna , Imran Ali Khan , Khalid K. Alharbi , Satti Vishnupriya , Divya Soni , Pratik Shah , Harshpreet Chandok , Mukesh Yadav , Anuraj Nayarisseri

Aim

Drugs in breast cancer treatment suffer resistance and drug efflux from ATP-binding cassette (ABC) efflux transporter protein. Drugs inhibiting BCRP suffer activity alteration due to sequence variants. It is imperative to investigate role of mutant variants using structure based aspects of drug binding.

Method

In present work, we included single nucleotide polymorphisms like F208S, S248P and F431L in BCRP structure and evaluated their role in alteration of drug binding affinities using computational approaches. Comparative modeling of BCRP 3D structure was achieved using various tools available followed by structure validation. Mutagenesis and its impact by SNPs was attained in 3D structure of BCRP. A set of selected and established BCRP inhibitors were further docked into binding site to record the drug resistance in mutant variants.

Results

Nucleotide binding (NB) domain (258 AA) and transmembrane (TM) domain (291 AA) of BCRP were modeled separately and assembled together to generate a single structure. Ramachandran Plot confirmed quality of modeled structures along with main chain and side chain parameters. Mutagenesis included three main variants (F208S, S248P and F431L) using Triton program. Molecular docking results showed inhibitor CID_25223199 binding effectively to wild and F431L mutant structure of BCRP while inhibitors CID_25223002 to F208S and CID_119373 to S248P.

Conclusion

Distortion in spatial arrangement of amino acids in BCRP protein due to mutations led to low efficacy in drug response with respect to wild isoform. Results of present work demand to probe pharmacogenomic aspects in drug development efforts for breast cancer.

目的治疗乳腺癌的药物存在atp结合盒(ABC)外排转运蛋白的耐药和药物外排。抑制BCRP的药物由于序列变异而发生活性改变。利用基于结构的药物结合方面来研究突变变体的作用是必要的。方法在BCRP结构中纳入F208S、S248P和F431L等单核苷酸多态性，利用计算方法评价其在药物结合亲和力改变中的作用。利用各种可用的工具实现BCRP三维结构的比较建模，然后进行结构验证。在BCRP的三维结构中获得了snp的诱变及其影响。将一组选定并建立的BCRP抑制剂进一步停靠到结合位点，记录突变变体的耐药性。结果BCRP的核苷酸结合(NB)结构域(258 AA)和跨膜结构域(TM)结构域(291 AA)分别建模并组装成单一结构。Ramachandran图通过主链和侧链参数验证了模型结构的质量。利用Triton程序诱变包括F208S、S248P和F431L三个主要变异体。分子对接结果显示，抑制剂CID_25223199与BCRP野生型和F431L突变体结构有效结合，抑制剂CID_25223002与F208S结合，CID_119373与S248P结合。结论与野生亚型相比，突变导致BCRP蛋白氨基酸空间排列扭曲，导致药物疗效较低。目前的工作结果需要探索药物基因组学方面的乳腺癌药物开发工作。

{"title":"Pharmacogenomics of drug resistance in Breast Cancer Resistance Protein (BCRP) and its mutated variants","authors":"Sugunakar Vuree , Nageswara Rao Dunna , Imran Ali Khan , Khalid K. Alharbi , Satti Vishnupriya , Divya Soni , Pratik Shah , Harshpreet Chandok , Mukesh Yadav , Anuraj Nayarisseri","doi":"10.1016/j.jopr.2013.06.020","DOIUrl":"10.1016/j.jopr.2013.06.020","url":null,"abstract":"<div><h3>Aim</h3><p>Drugs in breast cancer treatment suffer resistance and drug efflux from ATP-binding cassette (ABC) efflux transporter protein. Drugs inhibiting BCRP suffer activity alteration due to sequence variants. It is imperative to investigate role of mutant variants using structure based aspects of drug binding.</p></div><div><h3>Method</h3><p>In present work, we included single nucleotide polymorphisms like F208S, S248P and F431L in BCRP structure and evaluated their role in alteration of drug binding affinities using computational approaches. Comparative modeling of BCRP 3D structure was achieved using various tools available followed by structure validation. Mutagenesis and its impact by SNPs was attained in 3D structure of BCRP. A set of selected and established BCRP inhibitors were further docked into binding site to record the drug resistance in mutant variants.</p></div><div><h3>Results</h3><p>Nucleotide binding (NB) domain (258 AA) and transmembrane (TM) domain (291 AA) of BCRP were modeled separately and assembled together to generate a single structure. Ramachandran Plot confirmed quality of modeled structures along with main chain and side chain parameters. Mutagenesis included three main variants (F208S, S248P and F431L) using Triton program. Molecular docking results showed inhibitor CID_25223199 binding effectively to wild and F431L mutant structure of BCRP while inhibitors CID_25223002 to F208S and CID_119373 to S248P.</p></div><div><h3>Conclusion</h3><p>Distortion in spatial arrangement of amino acids in BCRP protein due to mutations led to low efficacy in drug response with respect to wild isoform. Results of present work demand to probe pharmacogenomic aspects in drug development efforts for breast cancer.</p></div>","PeriodicalId":16787,"journal":{"name":"Journal of Pharmacy Research","volume":"6 7","pages":"Pages 791-798"},"PeriodicalIF":0.0,"publicationDate":"2013-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.jopr.2013.06.020","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76188395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 18

Synthesis of novel indole based scaffolds holding pyrazole ring as anti-inflammatory and antioxidant agents 新型吡唑环吲哚基抗炎抗氧化支架的合成

Journal of Pharmacy Research

Pub Date : 2013-07-01 DOI: 10.1016/j.jopr.2013.07.002

Vishwanath Sharath , Honnaiah Vijay Kumar , Nagaraja Naik

Aim

To synthesize substituted indole based scaffolds having pyrazole ring and evaluate for their anti-inflammatory activity and antioxidant.

Method

The structures of newly synthesized compounds were elucidated by spectroscopic methods such as IR, ¹H NMR, ¹³C NMR, mass, ¹H NMR spectra and elemental analysis. Antioxidant assays like 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, 2,2-azino bis (3-ethylbenzothiazoline-6-sulfonic acid) ( ${ABTS}^{+}$ ) radical ion decolorization assay and lipid peroxidation activity (LPO) were performed. Anti-inflammatory activity was studied using linoleic acid as substrate and lipoxidase enzyme.

Results

Among the synthesized analogues compound 7d revealed broad-spectrum of antioxidant activity and on the other hand compound 7c exhibits a promising anti-inflammatory activity.

Conclusion

The achieved results prove that the distinctive compounds could serve as promising lead candidates and also for acclimatization and investigation to construct more active analogues.

目的合成具有吡唑环的取代吲哚基支架，并评价其抗炎和抗氧化活性。方法采用IR、1H NMR、13C NMR、质谱、1H NMR和元素分析等光谱方法对新合成化合物的结构进行鉴定。进行了2,2-二苯基-1-吡啶肼基(DPPH)自由基清除、2,2-氮基双(3-乙基苯并噻唑-6-磺酸)(ABTS+)自由基脱色和脂质过氧化活性(LPO)等抗氧化实验。以亚油酸为底物，用脂氧化酶对其抗炎活性进行了研究。结果化合物7d具有广谱抗氧化活性，化合物7c具有较好的抗炎活性。结论这些独特的化合物可作为有前途的先导化合物，并可用于驯化和研究构建更有活性的类似物。

{"title":"Synthesis of novel indole based scaffolds holding pyrazole ring as anti-inflammatory and antioxidant agents","authors":"Vishwanath Sharath , Honnaiah Vijay Kumar , Nagaraja Naik","doi":"10.1016/j.jopr.2013.07.002","DOIUrl":"10.1016/j.jopr.2013.07.002","url":null,"abstract":"<div><h3>Aim</h3><p>To synthesize substituted indole based scaffolds having pyrazole ring and evaluate for their anti-inflammatory activity and antioxidant.</p></div><div><h3>Method</h3><p>The structures of newly synthesized compounds were elucidated by spectroscopic methods such as IR, <sup>1</sup>H NMR, <sup>13</sup>C NMR, mass, <sup>1</sup>H NMR spectra and elemental analysis. Antioxidant assays like 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, 2,2-azino <em>bis</em> (3-ethylbenzothiazoline-6-sulfonic acid) (<span><math><mrow><msup><mrow><mtext>ABTS</mtext></mrow><mrow><mtext><mglyph></mglyph></mtext><mo>+</mo></mrow></msup></mrow></math></span>) radical ion decolorization assay and lipid peroxidation activity (LPO) were performed. Anti-inflammatory activity was studied using linoleic acid as substrate and lipoxidase enzyme.</p></div><div><h3>Results</h3><p>Among the synthesized analogues compound <strong>7d</strong> revealed broad-spectrum of antioxidant activity and on the other hand compound <strong>7c</strong> exhibits a promising anti-inflammatory activity.</p></div><div><h3>Conclusion</h3><p>The achieved results prove that the distinctive compounds could serve as promising lead candidates and also for acclimatization and investigation to construct more active analogues.</p></div>","PeriodicalId":16787,"journal":{"name":"Journal of Pharmacy Research","volume":"6 7","pages":"Pages 785-790"},"PeriodicalIF":0.0,"publicationDate":"2013-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.jopr.2013.07.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77493974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 21

Matrix type transdermal patches of captopril: Ex vivo permeation studies through excised rat skin 基质型卡托普利透皮贴剂:通过大鼠切除皮肤的体外渗透研究

Journal of Pharmacy Research

Pub Date : 2013-07-01 DOI: 10.1016/j.jopr.2013.07.003

Rajesh Sreedharan Nair, Tai Nyet Ling, Mohamed Saleem Abdul Shukkoor, Balamurugan Manickam

Background/objectives

Captopril, "an ACE inhibitor" has comparatively short elimination half life and its oxidation rate in dermal homogenate is significantly lower than that in intestinal homogenate. So as to enhance the bioavailability and to reduce the difficulties associated with captopril, it is decided to design a transdermal drug delivery system for this drug. So the objective of this present work is to formulate and evaluate the matrix type transdermal drug delivery systems of captopril, with different polymer combinations and penetration enhancers.

Methods

Eight formulations (F1–F8) were prepared by the solvent casting technique using varying proportions of polymers such as hydroxypropyl methylcellulose (HPMC), polyethylene glycol (PEG) 400, along with the permeation enhancers such as menthol and aloe vera at different concentrations.

Results

The FTIR results showed no abnormal peaks and thus concluded that no incompatibility between the drug and polymers. The skin irritation studies were performed on rabbits, the results showed no noticeable skin reactions, pointed out the compatibility of drug as well as polymer matrix with the skin. The uniformity of drug content was evidenced by low standard deviation (S.D) values. High folding endurance (>280) revealed that the prepared films have good flexibility. The weight of patches were uniform and thickness varied from 0.05 to 0.13 mm. Ex vivo permeation studies through excised rat skin were carried out using modified Franz diffusion cell, and the results showed that film (F6) containing HPMC and PEG 400 (1:1) with menthol as a permeation enhancer demonstrated the highest drug permeation (90.04%) at 24 h (p < 0.05) with the transdermal flux of 54.5 μg/cm²/h.

Conclusions

The formulation coded as F6 was found to be the ideal patch, shown the maximum drug permeation of 90.04% at the end of 24 h followed Higuchi diffusion kinetics.

背景/目的“ACE抑制剂”escaptopril的消除半衰期较短，其在真皮匀浆中的氧化速率明显低于在肠道匀浆中的氧化速率。为了提高卡托普利的生物利用度，减少卡托普利给药的困难，我们决定设计一种卡托普利经皮给药系统。因此，本研究的目的是通过不同的聚合物组合和渗透促进剂来制备和评价卡托普利的基质型透皮给药系统。方法采用溶剂铸造技术，采用羟丙基甲基纤维素(HPMC)、聚乙二醇(PEG) 400等不同配比的聚合物，以及不同浓度的薄荷醇和芦荟等渗透促进剂，制备了f1 ~ f8 8个配方。结果FTIR无异常峰，药物与聚合物不存在不相容性。对家兔进行皮肤刺激实验，未见明显的皮肤反应，说明药物及聚合物基质与皮肤的相容性良好。标准偏差(sd)值低，证明了药物含量的均匀性。高的折叠耐久性(>280)表明制备的薄膜具有良好的柔韧性。斑块重量均匀，厚度在0.05 ~ 0.13 mm之间。采用改良的Franz扩散池对大鼠皮肤进行体外渗透研究，结果表明，以薄荷醇为渗透促进剂，含HPMC和PEG 400(1:1)的膜(F6)在24 h时的药物渗透率最高(90.04%)(p <0.05)，透皮通量为54.5 μg/cm2/h。结论F6为理想贴剂，24 h时药物最大透度为90.04%，符合Higuchi扩散动力学。

{"title":"Matrix type transdermal patches of captopril: Ex vivo permeation studies through excised rat skin","authors":"Rajesh Sreedharan Nair, Tai Nyet Ling, Mohamed Saleem Abdul Shukkoor, Balamurugan Manickam","doi":"10.1016/j.jopr.2013.07.003","DOIUrl":"10.1016/j.jopr.2013.07.003","url":null,"abstract":"<div><h3>Background/objectives</h3><p>Captopril, \"an ACE inhibitor\" has comparatively short elimination half life and its oxidation rate in dermal homogenate is significantly lower than that in intestinal homogenate. So as to enhance the bioavailability and to reduce the difficulties associated with captopril, it is decided to design a transdermal drug delivery system for this drug. So the objective of this present work is to formulate and evaluate the matrix type transdermal drug delivery systems of captopril, with different polymer combinations and penetration enhancers.</p></div><div><h3>Methods</h3><p>Eight formulations (F1–F8) were prepared by the solvent casting technique using varying proportions of polymers such as hydroxypropyl methylcellulose (HPMC), polyethylene glycol (PEG) 400, along with the permeation enhancers such as menthol and <em>aloe vera</em> at different concentrations.</p></div><div><h3>Results</h3><p>The FTIR results showed no abnormal peaks and thus concluded that no incompatibility between the drug and polymers. The skin irritation studies were performed on rabbits, the results showed no noticeable skin reactions, pointed out the compatibility of drug as well as polymer matrix with the skin. The uniformity of drug content was evidenced by low standard deviation (S.D) values. High folding endurance (>280) revealed that the prepared films have good flexibility. The weight of patches were uniform and thickness varied from 0.05 to 0.13 mm. <em>Ex vivo</em> permeation studies through excised rat skin were carried out using modified Franz diffusion cell, and the results showed that film (F6) containing HPMC and PEG 400 (1:1) with menthol as a permeation enhancer demonstrated the highest drug permeation (90.04%) at 24 h (<em>p</em> < 0.05) with the transdermal flux of 54.5 μg/cm<sup>2</sup>/h.</p></div><div><h3>Conclusions</h3><p>The formulation coded as F6 was found to be the ideal patch, shown the maximum drug permeation of 90.04% at the end of 24 h followed Higuchi diffusion kinetics.</p></div>","PeriodicalId":16787,"journal":{"name":"Journal of Pharmacy Research","volume":"6 7","pages":"Pages 774-779"},"PeriodicalIF":0.0,"publicationDate":"2013-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.jopr.2013.07.003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73749167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 20

In vitro and in vivo antiproliferative potential of Cuscuta reflexa Roxb. 山茱萸体外和体内抗增殖潜能的研究。

Journal of Pharmacy Research

Pub Date : 2013-07-01 DOI: 10.1016/j.jopr.2013.06.005

Madhulika Bhagat , Jatinder Singh Arora , Ajit Kumar Saxena

Background

Cuscuta reflexa Roxb., (Convolvulaceae), is well known medicinal plant in Indian System of Medicine for various ailments. We have explored antiproliferative properties of Cuscuta reflexa (whole plant).

Methods

Three extracts (95% alcoholic, 50% hydro-alcoholic and aqueous) and four fractions (n-hexane, chloroform, n-butanol and aqueous) were prepared. In vitro cytotoxicity was observed by using SRB assay and in vivo antitumor activity was also performed using murine models.

Results

The alcoholic extract and its chloroform fraction were found to be most potent among three extracts and four fractions of alcoholic extract. It showed maximum cytotoxicity against human breast (MCF-7) cancer cell lines. The alcoholic extract showed significant (p < 0.05) tumor growth inhibition at 40 mg/kg which were 42.62% and 25.96% for Ehrlich tumor and Sarcoma −180 solid tumor model respectively. Similarly, chloroform fraction of alcoholic extract showed significant tumor growth inhibition of 48.98% and 44.11% for Ehrlich tumor and Sarcoma-180 solid tumor model at 10 mg/kg respectively.

Conclusion

This study indicates that the cytotoxic potential of Cuscuta reflexa lies in its alcoholic extract and chloroform fraction of alcoholic extract of the whole plant due to interference in cell proliferation.

背景cuscuta反射Roxb。(旋花科)，是印度医学系统中众所周知的药用植物，用于治疗各种疾病。我们对全株菟丝子的抗增殖特性进行了研究。方法制备三种提取物(95%乙醇、50%水乙醇和水)和四种馏分(正己烷、氯仿、正丁醇和水)。用SRB法观察其体外细胞毒性，用小鼠模型观察其体内抗肿瘤活性。结果在三种提取物和四种提取物中，酒精提取物及其氯仿部分的药效最强。对人乳腺(MCF-7)癌细胞具有最大的细胞毒性。酒精提取物显示显著(p <0.05)， 40 mg/kg对Ehrlich瘤和Sarcoma−180实体瘤模型的抑制率分别为42.62%和25.96%。同样，酒精提取物氯仿部分对Ehrlich瘤和saroma -180实体瘤模型的生长抑制作用分别为48.98%和44.11%。结论菟丝子的细胞毒作用主要表现在其醇提物和全株醇提物的氯仿部分对细胞增殖的干扰作用。

{"title":"In vitro and in vivo antiproliferative potential of Cuscuta reflexa Roxb.","authors":"Madhulika Bhagat , Jatinder Singh Arora , Ajit Kumar Saxena","doi":"10.1016/j.jopr.2013.06.005","DOIUrl":"10.1016/j.jopr.2013.06.005","url":null,"abstract":"<div><h3>Background</h3><p><em>Cuscuta reflexa</em> Roxb., (Convolvulaceae), is well known medicinal plant in Indian System of Medicine for various ailments. We have explored antiproliferative properties of <em>Cuscuta reflexa</em> (whole plant).</p></div><div><h3>Methods</h3><p>Three extracts (95% alcoholic, 50% hydro-alcoholic and aqueous) and four fractions (n-hexane, chloroform, n-butanol and aqueous) were prepared. <em>In vitro</em> cytotoxicity was observed by using SRB assay and <em>in vivo</em> antitumor activity was also performed using murine models.</p></div><div><h3>Results</h3><p>The alcoholic extract and its chloroform fraction were found to be most potent among three extracts and four fractions of alcoholic extract. It showed maximum cytotoxicity against human breast (MCF-7) cancer cell lines. The alcoholic extract showed significant (<em>p</em> < 0.05) tumor growth inhibition at 40 mg/kg which were 42.62% and 25.96% for Ehrlich tumor and Sarcoma −180 solid tumor model respectively. Similarly, chloroform fraction of alcoholic extract showed significant tumor growth inhibition of 48.98% and 44.11% for Ehrlich tumor and Sarcoma-180 solid tumor model at 10 mg/kg respectively.</p></div><div><h3>Conclusion</h3><p>This study indicates that the cytotoxic potential of <em>Cuscuta reflexa</em> lies in its alcoholic extract and chloroform fraction of alcoholic extract of the whole plant due to interference in cell proliferation.</p></div>","PeriodicalId":16787,"journal":{"name":"Journal of Pharmacy Research","volume":"6 7","pages":"Pages 690-695"},"PeriodicalIF":0.0,"publicationDate":"2013-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.jopr.2013.06.005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91193475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

Antinociceptive activity of the ethanolic extract of Persicaria acuminata Sach. 荆芥醇提物的抗伤活性研究。

Journal of Pharmacy Research

Pub Date : 2013-07-01 DOI: 10.1016/j.jopr.2013.07.005

Md. Saifuzzaman , Md. Sarowar Jahan Shamim , Kamanashis Mahaldar , Eunus Sheemul Ali , Md. Amirul Islam

Background

Persicaria acuminata Sach. (Family – Polygonaceae) commonly known as Bishkathali is a Bangladeshi native plant which is traditionally used in painful conditions.

Objective

The aim of the present study was to evaluate antinociceptive effect of the plant and to prove the scientific basis of traditional use.

Methods

The ethanolic extracts of leaf and stem of the plant were investigated using acetic acid induced writhing method on animal model.

Results

Oral administration of both leaf and stem extracts at the doses of 250 and 500 mg/kg body weight showed significant and dose-dependent inhibition of writhing response.

Conclusion

The study signifies the antinociceptive activity of the plant and supports its popular folkloric use in the management of pain.

背景:桃金体会。(科-蓼科)通常被称为比什卡塔利是一种孟加拉国本土植物，传统上用于痛苦的条件。目的评价该植物的抗伤性作用，为其传统应用提供科学依据。方法采用醋酸扭体法对植物叶和茎的乙醇提取物进行动物模型研究。结果叶提取物和茎提取物分别以250和500 mg/kg体重给药，均能显著抑制扭体反应，且呈剂量依赖性。结论该研究表明了该植物的抗伤害活性，并支持了其在治疗疼痛方面的流行民间应用。

引用次数: 2

Synthesis and pharmacological evaluation of some new dibenzo [b, f] [1, 4]thiazepines 几种新型二苯并[b, f][1,4]噻唑类药物的合成及药理评价

Journal of Pharmacy Research

Pub Date : 2013-07-01 DOI: 10.1016/j.jopr.2013.07.011

Sarita Pawar , Akhilesh Roy , Sanjay Wagh

Aim

In the present study ten dibenzothiazepines with a methylene bridge between tricyclic nucleus and the substituent at C-11 were synthesized in order to investigate their antipsychotic activity. Some of the derivatives showed significant activity.

Methods

The title compounds were synthesized by condensation of 11-piperazinyl-dibenzothiazepine with the substituted benzyl halides in presence of triethylamine and 1,4-dioxane. The structures of the derivatives were elucidated by spectral analysis. The antipsychotic activity of the synthesized derivatives was evaluated using haloperidol induced catalepsy and lithium induced head twitches.

Results

In SSP-9 treated group, maximum catalepsy was noted 30 min after haloperidol. Lithium induced 40.2 ± 1.655 head twitches in 1 h. Clozapine (5 mg per kg) and SSP-9 (5 mg per kg) reduced the number of head twitches to 10 ± 0.7071 and 14.8 ± 0.8602, respectively.

Conclusion

The results demonstrated that the derivative SSP-9 possesses significant in vitro antipsychotic activity when compared with standard clozapine. Therefore, compound SSP-9 prototype could be considered as novel antipsychotic agent for further developing new atypical antipsychotics.

目的合成了10种在三环核和C-11取代基之间有亚甲基桥的二苯并噻唑类药物，研究其抗精神病活性。其中一些衍生品表现出显著的活性。方法在三乙胺和1,4-二恶烷的存在下，将11-哌嗪基二苯并噻唑与取代的苄基卤化物缩合合成上述化合物。通过光谱分析对衍生物的结构进行了表征。合成衍生物的抗精神病活性通过氟哌啶醇诱导的猝厥和锂诱导的头抽搐来评估。结果SSP-9治疗组在氟哌啶醇治疗30 min后出现最大程度的麻痹。锂在1 h内诱发40.2±1.655次头抽搐，氯氮平(5 mg / kg)和SSP-9 (5 mg / kg)分别使头抽搐次数减少至10±0.7071次和14.8±0.8602次。结论与标准氯氮平相比，SSP-9衍生物具有明显的体外抗精神病活性。因此，复方SSP-9原型可作为进一步开发新型非典型抗精神病药物的新型抗精神病药物。

{"title":"Synthesis and pharmacological evaluation of some new dibenzo [b, f] [1, 4]thiazepines","authors":"Sarita Pawar , Akhilesh Roy , Sanjay Wagh","doi":"10.1016/j.jopr.2013.07.011","DOIUrl":"10.1016/j.jopr.2013.07.011","url":null,"abstract":"<div><h3>Aim</h3><p>In the present study ten dibenzothiazepines with a methylene bridge between tricyclic nucleus and the substituent at C-11 were synthesized in order to investigate their antipsychotic activity. Some of the derivatives showed significant activity.</p></div><div><h3>Methods</h3><p>The title compounds were synthesized by condensation of 11-piperazinyl-dibenzothiazepine with the substituted benzyl halides in presence of triethylamine and 1,4-dioxane. The structures of the derivatives were elucidated by spectral analysis. The antipsychotic activity of the synthesized derivatives was evaluated using haloperidol induced catalepsy and lithium induced head twitches.</p></div><div><h3>Results</h3><p>In SSP-9 treated group, maximum catalepsy was noted 30 min after haloperidol. Lithium induced 40.2 ± 1.655 head twitches in 1 h. Clozapine (5 mg per kg) and SSP-9 (5 mg per kg) reduced the number of head twitches to 10 ± 0.7071 and 14.8 ± 0.8602, respectively.</p></div><div><h3>Conclusion</h3><p>The results demonstrated that the derivative SSP-9 possesses significant in vitro antipsychotic activity when compared with standard clozapine. Therefore, compound SSP-9 prototype could be considered as novel antipsychotic agent for further developing new atypical antipsychotics.</p></div>","PeriodicalId":16787,"journal":{"name":"Journal of Pharmacy Research","volume":"6 7","pages":"Pages 756-760"},"PeriodicalIF":0.0,"publicationDate":"2013-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.jopr.2013.07.011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87720282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Acute oral toxicity studies of the standardized methanolic extract of Phyllanthus amarus Schum & Thonn 毛茛标准化甲醇提取物的急性口服毒性研究

Journal of Pharmacy Research

Pub Date : 2013-07-01 DOI: 10.1016/j.jopr.2013.04.020

S.K. Kushwaha , A. Dashora , N. Dashora , J.R. Patel , M.L. Kori

Objectives

To determine the acute toxicity of standardized methanolic extract of Phyllanthus amarus in vivo in female albino rats.

Methods

Treated group of animals were administrated 300, 600, 2000 and 5000 mg/kg body weight of extract orally and the control group received standard laboratory diet and water ad libitum following OECD guideline 423 with some modifications. All animals were sacrificed after 14 days of treatment.

Results

The extract was standardized by HPLC to contain phyllanthin and hypophyllanthin. No mortality was noted and the study exhibited no significant changes in general behavior, body weight, gross appearance of internal organs, hematological and biochemical parameters and the histological profile of liver also indicated the nontoxic nature of this drug. Biochemical studies showed no significant change in the levels of ALT, AST, albumin, triglycerides, cholesterol and albumin. There were no evidence found about congestion of sinusoids, hemorrhage, hepatocytes, fatty changes, centrilobular necrosis and the changes in number of Kupffer cells in the liver. There was no increase of blood pressure and does not induce any nephrotoxicity and acute severe hepatotoxicity.

Conclusion

The present study provides pivotal evidences for ascertaining the safety of the standardized MEPA (LD₅₀ > 5000 mg/kg) that could be used as tonic or food supplement in folklore medicine.

目的研究白化病雌性大鼠的急性体内毒性。方法治疗组分别口服300、600、2000和5000 mg/kg体重的提取物，对照组按照OECD指南423进行修改，给予标准实验室饲料和水。治疗14天后，所有动物均被处死。结果经高效液相色谱法鉴定，提取物中含有叶黄素和茶黄素。没有死亡记录，研究显示一般行为、体重、内脏器官大体外观、血液学和生化参数以及肝脏组织学特征没有显著变化，也表明该药物无毒。生化研究显示ALT、AST、白蛋白、甘油三酯、胆固醇和白蛋白水平无明显变化。未见肝窦充血、出血、肝细胞、脂肪改变、小叶中心坏死及肝内库普弗细胞数目改变。血压未升高，未引起肾毒性和急性严重肝毒性。结论本研究为确定标准化MEPA (LD50 >5000 mg/kg)，可作为民间医学的滋补品或食品补充剂。

{"title":"Acute oral toxicity studies of the standardized methanolic extract of Phyllanthus amarus Schum & Thonn","authors":"S.K. Kushwaha , A. Dashora , N. Dashora , J.R. Patel , M.L. Kori","doi":"10.1016/j.jopr.2013.04.020","DOIUrl":"10.1016/j.jopr.2013.04.020","url":null,"abstract":"<div><h3>Objectives</h3><p>To determine the acute toxicity of standardized methanolic extract of <em>Phyllanthus amarus in vivo</em> in female albino rats.</p></div><div><h3>Methods</h3><p>Treated group of animals were administrated 300, 600, 2000 and 5000 mg/kg body weight of extract orally and the control group received standard laboratory diet and water <em>ad libitum</em> following OECD guideline 423 with some modifications. All animals were sacrificed after 14 days of treatment.</p></div><div><h3>Results</h3><p>The extract was standardized by HPLC to contain phyllanthin and hypophyllanthin. No mortality was noted and the study exhibited no significant changes in general behavior, body weight, gross appearance of internal organs, hematological and biochemical parameters and the histological profile of liver also indicated the nontoxic nature of this drug. Biochemical studies showed no significant change in the levels of ALT, AST, albumin, triglycerides, cholesterol and albumin. There were no evidence found about congestion of sinusoids, hemorrhage, hepatocytes, fatty changes, centrilobular necrosis and the changes in number of Kupffer cells in the liver. There was no increase of blood pressure and does not induce any nephrotoxicity and acute severe hepatotoxicity.</p></div><div><h3>Conclusion</h3><p>The present study provides pivotal evidences for ascertaining the safety of the standardized MEPA (LD<sub>50</sub> > 5000 mg/kg) that could be used as tonic or food supplement in folklore medicine.</p></div>","PeriodicalId":16787,"journal":{"name":"Journal of Pharmacy Research","volume":"6 7","pages":"Pages 720-724"},"PeriodicalIF":0.0,"publicationDate":"2013-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.jopr.2013.04.020","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86615106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 12

Cytotoxic and antioxidant activities of marine sponge diversity at Pecaron Bay Pasir Putih Situbondo East Java, Indonesia 东爪哇Pecaron湾Pasir Putih sitbondo海域海绵多样性的细胞毒性和抗氧化活性

Journal of Pharmacy Research

Pub Date : 2013-07-01 DOI: 10.1016/j.jopr.2013.07.001

Syamsudin Abdillah , Awik Puji Dyah Nurhayati , Sri Nurhatika , Edwin Setiawan , Wan Lelly Heffen

Objective

A study on the cytotoxic and antioxidant activities of Sponges collected from Pecaron Bay Pasir Putih Situbondo was conducted. This study aimed at screening the hydro-ethanolic extracts of 7 sponge species: Callyspongia sp, Acanthella sp and Xestospongia sp colleted at the Pecaron Situbondo, East Java, Indonesia for antiproliferative and antioxidant activities.

Methods

After collection, the species were immediately immersed in ethanol and stored at low temperatures (−20 °C) until use. Cytotoxic assay was conducted using MTT methods for some cancerous cells, including T47D, Casky and HT-29 meanwhile antioxidant assay was conducted using DPPH method.

Results

the extracts from species A. suberitoides has the highest toxicity compare to another species which valued level on tumor cell lines (HT-29, T47D and Casky). Antioxidant assay using DPPH method found that only Aaptos suberitoides that had been identified to show strong activity due to IC₅₀ value of <30 μg/mL; meanwhile Fascaplysinopsis reticulata, Acanthella sp, Petrosia contignata and Xestospongia exigua showed moderate antioxidant activity with a IC₅₀ < 100 μg/mL. Xestospongia sp, Callyspongia sp showed a value of IC₅₀ > 100 μg/mL.

Conclusion

The study showed that Xestospongia sp, Fascaplysinopsis reticulata, Callyspongia sp, Petrosia contignata, Aaptos suberitoides were highly potential to develop for isolation of bioactive compounds as anticancer and antioxidant agents.

目的研究Pecaron Bay Pasir Putih sitbondo海绵体的细胞毒和抗氧化活性。本研究旨在对采自印度尼西亚东爪哇Pecaron sitbondo的7种海绵(Callyspongia sp、Acanthella sp和Xestospongia sp)的水乙醇提取物进行抗增殖和抗氧化活性筛选。方法采集后立即用乙醇浸泡，低温保存(- 20℃)备用。采用MTT法对部分癌细胞T47D、Casky、HT-29进行细胞毒试验，同时采用DPPH法进行抗氧化试验。结果对肿瘤细胞株(HT-29、T47D和Casky)的毒性最高。采用DPPH法进行抗氧化实验，发现只有经鉴定的亚种Aaptos具有较强的抗氧化活性，IC50值为30 μg/mL;网状Fascaplysinopsis reticulata、棘皮藻(Acanthella sp .)、木犀草(Petrosia congnata)和木犀草(Xestospongia exigua)的抗氧化活性中等，IC50 +;100μg / mL。Xestospongia sp, Callyspongia sp的IC50 >值;100μg / mL。结论研究表明，海绒菌属(Xestospongia sp)、网状筋膜鞘菌属(Fascaplysinopsis reticulata)、粘海绵菌属(Callyspongia sp)、褐藻属(Petrosia congnata)、亚亚绒螯虾属(Aaptos sub亚亚绒螯虾属)具有很强的抗癌和抗氧化活性化合物开发潜力。

{"title":"Cytotoxic and antioxidant activities of marine sponge diversity at Pecaron Bay Pasir Putih Situbondo East Java, Indonesia","authors":"Syamsudin Abdillah , Awik Puji Dyah Nurhayati , Sri Nurhatika , Edwin Setiawan , Wan Lelly Heffen","doi":"10.1016/j.jopr.2013.07.001","DOIUrl":"10.1016/j.jopr.2013.07.001","url":null,"abstract":"<div><h3>Objective</h3><p>A study on the cytotoxic and antioxidant activities of Sponges collected from Pecaron Bay Pasir Putih Situbondo was conducted. This study aimed at screening the hydro-ethanolic extracts of 7 sponge species: <em>Callyspongia</em> sp, <em>Acanthella</em> sp and <em>Xestospongia</em> sp colleted at the Pecaron Situbondo, East Java, Indonesia for antiproliferative and antioxidant activities.</p></div><div><h3>Methods</h3><p>After collection, the species were immediately immersed in ethanol and stored at low temperatures (−20 °C) until use. Cytotoxic assay was conducted using MTT methods for some cancerous cells, including T47D, Casky and HT-29 meanwhile antioxidant assay was conducted using DPPH method.</p></div><div><h3>Results</h3><p>the extracts from species <em>A. suberitoides</em> has the highest toxicity compare to another species which valued level on tumor cell lines (HT-29, T47D and Casky). Antioxidant assay using DPPH method found that only <em>Aaptos suberitoides</em> that had been identified to show strong activity due to IC<sub>50</sub> value of <30 μg/mL; meanwhile <em>Fascaplysinopsis reticulata</em>, <em>Acanthella</em> sp, <em>Petrosia contignata</em> and <em>Xestospongia exigua</em> showed moderate antioxidant activity with a IC<sub>50</sub> < 100 μg/mL. <em>Xestospongia</em> sp<em>, Callyspongia</em> sp showed a value of IC<sub>50</sub> > 100 μg/mL.</p></div><div><h3>Conclusion</h3><p>The study showed that <em>Xestospongia</em> sp<em>, Fascaplysinopsis reticulata, Callyspongia</em> sp, <em>Petrosia contignata</em>, <em>Aaptos suberitoides</em> were highly potential to develop for isolation of bioactive compounds as anticancer and antioxidant agents.</p></div>","PeriodicalId":16787,"journal":{"name":"Journal of Pharmacy Research","volume":"6 7","pages":"Pages 685-689"},"PeriodicalIF":0.0,"publicationDate":"2013-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.jopr.2013.07.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74629095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 24

Interpretation of consumer's perception on readability of Consumer Medical Information Leaflets on obesity and lipid lowering drugs with standard methods 用标准方法解读消费者对减肥药降脂药《消费者医疗信息手册》可读性的认知

Journal of Pharmacy Research

Pub Date : 2013-07-01 DOI: 10.1016/j.jopr.2013.07.024

Elizabeth M. Mathew , Kingston Rajiah , Krishana Kumar Sharma

Aim

Printed education materials are often used to augment healthcare professional's verbal information to consumers so it serves as an important component of symptom management. They also enhance the teaching process and can be used by consumers as a home reference. This study was aimed to interpret consumers' perception on Consumer Medical Information Leaflets (CMILs) on obesity and lipid lowering drugs, according to the standard formulae such as Flesch Reading Ease (FRE), Flesch–Kincaid Grade Level (FK-GL).

Method

The study was conducted over a period of 3 years in community pharmacy settings in Tamil Nadu, India. CMILs were interpreted by using the formulae such as Flesch Reading Ease (FRE) and Flesch–Kincaid Grade Level (FK-GL). Among the 1800 consumers, 300 consumers were excluded from the study due to lack of interest.

Results

Data revealed the consumer's perception on readability of Consumer Medical Information Leaflets on obesity and lipid lowering drugs based consumers rating.

Conclusions

Pharmaceutical companies (leaflets providers) are not taking the reading level of consumers into consideration which may not achieve the intended purpose. There is a need for developing CMILs having good readability score according to Indian set up.

目的打印的教育材料通常用于增加医疗保健专业人员的口头信息给消费者，因此它是症状管理的重要组成部分。它们还可以提高教学过程，并可被消费者用作家庭参考。本研究旨在以Flesch Reading Ease (FRE)、Flesch - kincaid Grade Level (FK-GL)等标准配方，解读消费者对《消费者医疗信息手册》(CMILs)中减肥降脂药物的认知。方法在印度泰米尔纳德邦的社区药房进行为期3年的研究。使用Flesch Reading Ease (FRE)和Flesch - kincaid Grade Level (FK-GL)等公式解释cmil。在1800名消费者中，有300名消费者因缺乏兴趣而被排除在研究之外。结果数据揭示了消费者对减肥药、降脂药《消费者医疗信息手册》可读性的认知。结论制药公司(宣传单提供者)没有考虑到消费者的阅读水平，可能达不到预期目的。根据印度的设置，有必要开发具有良好可读性评分的cmil。

{"title":"Interpretation of consumer's perception on readability of Consumer Medical Information Leaflets on obesity and lipid lowering drugs with standard methods","authors":"Elizabeth M. Mathew , Kingston Rajiah , Krishana Kumar Sharma","doi":"10.1016/j.jopr.2013.07.024","DOIUrl":"10.1016/j.jopr.2013.07.024","url":null,"abstract":"<div><h3>Aim</h3><p>Printed education materials are often used to augment healthcare professional's verbal information to consumers so it serves as an important component of symptom management. They also enhance the teaching process and can be used by consumers as a home reference. This study was aimed to interpret consumers' perception on Consumer Medical Information Leaflets (CMILs) on obesity and lipid lowering drugs, according to the standard formulae such as Flesch Reading Ease (FRE), Flesch–Kincaid Grade Level (FK-GL).</p></div><div><h3>Method</h3><p>The study was conducted over a period of 3 years in community pharmacy settings in Tamil Nadu, India. CMILs were interpreted by using the formulae such as Flesch Reading Ease (FRE) and Flesch–Kincaid Grade Level (FK-GL). Among the 1800 consumers, 300 consumers were excluded from the study due to lack of interest.</p></div><div><h3>Results</h3><p>Data revealed the consumer's perception on readability of Consumer Medical Information Leaflets on obesity and lipid lowering drugs based consumers rating.</p></div><div><h3>Conclusions</h3><p>Pharmaceutical companies (leaflets providers) are not taking the reading level of consumers into consideration which may not achieve the intended purpose. There is a need for developing CMILs having good readability score according to Indian set up.</p></div>","PeriodicalId":16787,"journal":{"name":"Journal of Pharmacy Research","volume":"7 7","pages":"Pages 606-610"},"PeriodicalIF":0.0,"publicationDate":"2013-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.jopr.2013.07.024","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85153942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

Molecular modelling studies of Histone Deacetylase inhibitors as anticancer agents 组蛋白去乙酰化酶抑制剂抗癌作用的分子模拟研究

Journal of Pharmacy Research

Pub Date : 2013-07-01 DOI: 10.1016/j.jopr.2013.07.017

Sibi Narayanan , D. Velmurugan

Background

Cancer causes death to over 7.6 million people every year. The disease can be classified as cells' uncontrolled division. This uncontrolled division of cells or uncontrolled growth is caused by DNA damage. This eventually results in genes mutations, which encodes cell division controlling proteins. Histone deacetylase (HDAC) is one among the principal targets for the anticancer drugs.

Methods

Molecular docking studies of nearly 60 Trichostatin A, SuberoylAnilide Hydroxamic Acid and Sulfonamide anilides which show good inhibitory activity against HDAC were carried out using GLIDE program of Schrödinger Suite 2009. Comparison of docking scores of the compounds with their respective QSAR IC₅₀ have also been made.

Results

From Trichostatin A and SuberoylAnilide Hydroxamic Acid analogues binding results, it was found that HDAC conformational changes are based on the ligand binding. C/N/O atoms present in the aliphatic chains of the analogues interacted well with the Zn²⁺ metal ion and active site amino acid residues to disrupt the enzymatic activity of target protein HDAC.

Conclusion

Analogue inhibition taken into study with the target protein HDAC assures to be an advantageous therapeutic approach in cancer treatment.

癌症每年导致超过760万人死亡。这种疾病可归类为细胞不受控制的分裂。这种不受控制的细胞分裂或不受控制的生长是由DNA损伤引起的。这最终导致基因突变，从而编码控制细胞分裂的蛋白质。组蛋白去乙酰化酶(HDAC)是抗癌药物的主要靶点之一。方法利用Schrödinger Suite 2009的GLIDE软件对近60种对HDAC具有良好抑制活性的曲古霉素A、亚羟肟酸和磺胺类苯胺进行分子对接研究。并将化合物的对接分数与其QSAR IC50进行了比较。结果从曲古霉素A与亚羟肟酸类似物的结合结果中发现，HDAC的构象变化是以配体结合为基础的。类似物的脂肪链上的C/N/O原子与Zn2+金属离子和活性位点氨基酸残基相互作用良好，破坏靶蛋白HDAC的酶活性。结论利用靶蛋白HDAC进行类似物抑制研究，有望成为治疗肿瘤的有效途径。

{"title":"Molecular modelling studies of Histone Deacetylase inhibitors as anticancer agents","authors":"Sibi Narayanan , D. Velmurugan","doi":"10.1016/j.jopr.2013.07.017","DOIUrl":"10.1016/j.jopr.2013.07.017","url":null,"abstract":"<div><h3>Background</h3><p>Cancer causes death to over 7.6 million people every year. The disease can be classified as cells' uncontrolled division. This uncontrolled division of cells or uncontrolled growth is caused by DNA damage. This eventually results in genes mutations, which encodes cell division controlling proteins. Histone deacetylase (HDAC) is one among the principal targets for the anticancer drugs.</p></div><div><h3>Methods</h3><p>Molecular docking studies of nearly 60 Trichostatin A, SuberoylAnilide Hydroxamic Acid and Sulfonamide anilides which show good inhibitory activity against HDAC were carried out using GLIDE program of Schrödinger Suite 2009. Comparison of docking scores of the compounds with their respective QSAR IC<sub>50</sub> have also been made.</p></div><div><h3>Results</h3><p>From Trichostatin A and SuberoylAnilide Hydroxamic Acid analogues binding results, it was found that HDAC conformational changes are based on the ligand binding. C/N/O atoms present in the aliphatic chains of the analogues interacted well with the Zn<sup>2+</sup> metal ion and active site amino acid residues to disrupt the enzymatic activity of target protein HDAC.</p></div><div><h3>Conclusion</h3><p>Analogue inhibition taken into study with the target protein HDAC assures to be an advantageous therapeutic approach in cancer treatment.</p></div>","PeriodicalId":16787,"journal":{"name":"Journal of Pharmacy Research","volume":"7 7","pages":"Pages 611-620"},"PeriodicalIF":0.0,"publicationDate":"2013-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.jopr.2013.07.017","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85186120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0