bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthesis and Structural Elucidation of Novel Benzothiazole Derivatives as Anti-tubercular Agents: In-silico Screening for Possible Target Identification
Authors: Venugopala Katharigatta N. , Chandrashekharappa Sandeep , Pillay Melendhran , Bhandary Subhrajyoti , Kandeel Mahmoud , Mahomoodally Fawzi M. , Morsy Mohamed A. , Chopra Deepak , Aldhubiab Bandar E. , Attimarad Mahesh , Alwassil Osama I. , Harsha Sree , Mlisana Koleka , Odhav Bharti 
Published: September 2018

Background:
Benzothiazole derivatives are known for anti-TB properties. Based on the
known anti-TB benzothiazole pharmacophore, in the present study, we described the synthesis,
structural elucidation, and anti-tubercular screening of a series of novel benzothiazole (BNTZ) derivatives
(BNTZ 1–7 and BNTZ 8–13).

Objective:
The study aims to carry out the development of benzothiazole based anti-TB compounds.

Methods:
Title compounds are synthesized by microwave method and purified by column chromatography.
Characterization of the compounds is achieved by FT-IR, NMR (1H and 13C), LCMS
and elemental analysis. Screening of test compounds for anti-TB activity is achieved by Resazurin
Microplate Assay (REMA) Plate method.

Results:
It was noted that the BNTZ compound with an isoquinoline nucleus (BNTZ 9) exhibited
remarkable anti-tubercular activity at 8 &µg/mL against both the susceptible strain H37Rv and the
multi-drug resistant tuberculosis strains of Mycobacterium tuberculosis. On the other hand, the
BNTZ compound with a naphthalene nucleus (BNTZ 2) revealed anti-tubercular activity at 6
µg/mL and 11 &µg/mL against both the susceptible strain H37Rv and the multi-drug resistant tuberculosis
strains of M. tuberculosis, respectively. One of the selected BNTZ derivatives BNTZ 13
was used for single crystal X-ray studies.

Conclusion:
To identify the appropriate target for potent BNTZ compounds from the series, molecular
modeling studies revealed the multiple strong binding of several BNTZs with mycobacterium
lysine-ɛ-aminotransferase and decaprenyl-phosphoryl-β-D-ribose 2&'-oxidase. The interaction
is derived by forming favorable hydrogen bonds and stacking interactions. This new class of
BNTZ compounds gave promising anti-tubercular actions in the low micromolar range, and can be
further optimized on a structural basis to develop promising, novel, BNTZ pharmacophore-based
anti-tubercular drugs.
Design, Synthesis, and Biological Evaluation of Novel Thiazolyl Substituted Bis-pyrazole Oxime Derivatives with Potent Antitumor Activities by Selectively Inducing Apoptosis and ROS in Cancer Cells
Authors: Xiong Biao , Chen Shi , Zhu Peng , Huang Meiling , Gao Weijie , Zhu Rui , Qian Jianqiang , Peng Yanfu , Zhang Yanan , Dai Hong , Ling Yong 
Published: September 2018

Background:
A large number of pyrazole derivatives have different biological activities
such as anticancer, antimicrobial, anti-inflammatory, analgesic and antiepileptic activity.
Among them, pyrazole oximes have attracted much attention due to their potential pharmacological
activities, particularly anticancer activities.

Objective:
Our goal is to synthesize novel thiazolyl substituted bis-pyrazole oxime derivatives
with potent antitumor activities by selectively inducing apoptosis and Reactive Oxygen Species
(ROS) accumulation in cancer cells.

Methods:
Eighteen bis-pyrazole oximes were synthesized by conjugating thiazolyl substituted
pyrazoles with pyrazoxime. The target compounds were characterized by 1HNMR, 13C NMR, and
HRMS, and screened for their antiproliferative activity against four cancer cells in MTT assay.
The most potent compound was examined for its inhibitory effect and ROS accumulation in both
cancer cells HCT116 and normal intestinal epithelial cells CCD841. Finally, the most potent
compound was further evaluated for its apoptotic induction by flow cytometry analysis and immunoblot
analysis of apoptosis-related proteins and DNA damage proteins.

Results:
Most compounds displayed potent antiproliferative activity against four cancer cell lines
in vitro, displaying potencies superior to 5-FU. In particular, the most potent compound 13l selectively
inhibited proliferation of colorectal cancer HCT116 cells but not normal colon CCD841
cells. Furthermore, compound 13l also selectively promoted intracellular ROS accumulation in
HCT116 which was involved in 13l inhibition of cancer cell proliferation and induction of cell
apoptosis. Finally, compound 13l also dose-dependently induced cancer cell apoptosis by regulating
apoptotic and DNA damage related proteins expressions.

Conclusion:
Our synthetic bis-pyrazole oxime derivatives possess potent antitumor activities by
selectively inducing apoptosis and ROS accumulation in cancer cells, which may hold great
promise as therapeutic agents for the treatment of human cancers.
A Novel Simultaneous Estimation of Sofosbuvir and Velpatasvir in Human Plasma by Liquid Chromatography Tandem-Mass Spectrometry after Protein Precipitation Method
Authors: Narenderan S.T. , Babu Basuvan , Gokul T. , Meyyanathan Subramania Nainar 
Published: September 2018

Objective:
The aim of the present work is to achieve a novel highly sensitive chromatographic
method for the simultaneous determination of hepatitis C agents, sofosbuvir and velpatasvir
from human plasma using ritonavir as an internal standard.

Methods:
Chromatographic separation was achieved using Hypersil C18 column (50mm x 4.6mm, 3μm)
with an isocratic elution mode using the mobile phase composition 10 mM ammonium formate buffer
(pH 5.0): acetonitrile (20:80 v/v) pumped at a flow rate of 0.5 ml/min. The detection was carried out by
tandem mass spectrometry using Multiple Reaction Monitoring (MRM) positive Electrospray Ionization
(ESI) with proton adducts at m/z 530.10 > 243.10, 883.40 > 114.0 and 721.25 > 197.0.

Results:
The method validated as per USFDA guidelines with respect to linearity, accuracy, and precision
was found to be acceptable over the concentration range of 0.2–2000 ng/ml and 5-2000 ng/ml for
sofosbuvir and velpatasvir respectively and the method was found to be highly sensitive and selective.

Conclusion:
The developed tandem mass spectrometric method is robust and can be applied for the
monitoring of plasma levels of the analyzed drug in preclinical and clinical pharmacokinetic studies.
Tissue Distribution of Active Principles from Alpiniae Oxyphyllae Fructus Extract: An Experimental Study in Rats
Authors: Wen Qi , Li Hai-Long , Mai Shi-Ying , Tan Yin-Feng , Chen Feng 
Published: September 2018

Background:
Alpiniae Oxyphyllae Fructus (Yizhi in Chinese) have been widely used as an
herbal medicine for the treatment of diuresis, enuresis and diarrhea in China. Many studies have deciphered
some potential underlying mechanisms for its anti-diarrheal effects. However, tissue distribution
of Yizhi constituents is warranted because pharmacological receptors are frequently located in tissues.
Moreover, it is also interesting to know about the potential correlation between behavior in drug distribution
and the observed pharmacological response. The aim of this study is to investigate tissue distribution
behaviors of Yizhi constituents after oral administration of Yizhi extract to rats, focusing on 10
active principles.

Methods:
Twenty four male Sprague Dawley rats were given orally the Yizhi extract and fourteen tissue
samples were collected after being killed by bleeding from the abdominal aorta under ether anesthesia
at different time-points. The resulting tissues were excised and homogenized. Based on our previous
reports, liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) was used to quantify
the target analytes, as well as phase II metabolites, in the various biosamples.

Results:
Almost all the targeted Yizhi active principles and some glucuronidated metabolites were
qualitatively measured in rat stomach, small intestine, large intestine, as well as liver. Nootkatone,
yakuchinone A and tectochrysin were observed in the rat brain. In other rat tissues, these analytes had
lower exposure or could not be detected. Consistently, quantitative analysis revealed that the Yizhi active
principles dominantly distributed into gastrointestinal tissues followed by liver, the overall exposure
levels ranking as follows: stomach > small intestine > large intestine > liver. Tissue concentrationtime
profiles of the test active principles in rat stomach, small intestine, and large intestine were bimodal
with two concentration peaks occurring at 0.5 and 4h after oral administration, respectively. The
exposure levels in rat kidney and bladder were quite low.

Conclusion:
The active principles of Yizhi were specially distributed into gastrointestinal tissues after
oral administration of its ethanol extract to rats. The tissue distribution behaviors partly supported its
anti-diarrheal effects from a pharmacokinetic opinion. This paper will be useful as the starting point for
studying the pharmacological activities of this traditional herb.
Non-Invasive Extraction of Gabapentin for Therapeutic Drug Monitoring by Reverse Iontophoresis: Effect of pH, Ionic Strength, and Polyethylene Glycol 400 in the Receiving Medium
Authors: Giri Tapan Kumar , Chakrabarty Subhasis , Ghosh Bijaya 
Published: September 2018

Background:
Monitoring of plasma concentrations is a necessity for narrow therapeutic index
potent drugs. Development of non-invasive methods can save the patients from the trauma of needles
and hence is considered as a research priority.

Introduction:
Gabapentin, an anti-epileptic drug requires therapeutic monitoring because of its narrow
therapeutic index. The objective of the study was to develop a suitable method for the non-invasive
extraction of gabapentin for the same.

Methods:
Transdermal reverse iontophoresis was performed using pig ear skin as a barrier membrane.
Three compartment iontophoretic cells were used for the extraction study. Extractions were carried out
under low intensity electric field (current intensity- 0.5 mA/cm2, electrical field approximately 5 V).
The donor compartment was charged with aqueous gabapentin (10 µg/ml in phosphate buffer of pH
7.4). For studying the effect of receiving vehicle (pH, ionic strength, and enhancer) on the extraction
efficiency of gabapentin, the two receiver chambers were charged with media having varying concentration
of these factors. Drug content was determined by HPLC.

Results:
Compared to other pHs, cumulative extraction of gabapentin at pH 5 was significantly higher
at both anode and cathode (p<0.001). At low ionic strength, extraction of gabapentin increased linearly
with the increase in concentration of ions up to a certain value but at very high ionic strength the pattern
reversed. Similar results were obtained with enhancer (polyethylene glycol 400). Extraction increased
with increase in polyethylene glycol 400 up to 3% and then decreased.

Conclusion:
Extraction flux can be optimized by manipulation of the receiver media.
Preparation and Characterization of Four Major Novel Degradation Products of Pralatrexate Injection and Validation of HPLC-UV Method
Authors: Prabhakara Sastry Regella Venkata Rama , Venkatesan Chidambaram Subramanian , Sastry Bhetanabhotla Sarveswara , Sathiyanarayanan Singaram , Murali Sanapati 
Published: September 2018

Background:
Four major degradation products (1-4) of pralatrexate injection were formed
under hydrolytic and light stress conditions. The impurities 1 and 2 were the potential photo degradation
products and the impurities 3 and 4 were the potential hydrolytic degradation products.

Objective:
To prepare and characterize the novel degradation impurities 1, 2, 3 and 4 of pralatrexate
injection using NMR, HR MS and IR techniques; and to develop and validate stability indicating analytical
reverse phase HPLC-UV method for quantitative simultaneous determination of potential
degradation impurities, related substances of pralatrexate and pralatrexate active in pralatrexate liquid
formulation.

Methods:
Gradient HPLC-UV method was developed for the quantification of degradation impurities,
related substances and pralatrexate in pralatrexate injection. The separation was achieved on C18 column
(250 mm X 4.6 mm, 5µm) using a mobile phase composed of sodium dihydrogen phosphate
monohydrate in water (pH 3.0; 0.01M) and methanol. The components were monitored by the UVvisible
detector at 242 nm with a flow rate of 1.0 mL/min.

Results:
The method validation parameters such as accuracy, selectivity, linearity, LOD, LOQ, precision,
ruggedness and robustness were demonstrated successfully for pralatrexate and its degradation
impurities. The stability-indicating capability of the developed HPLC method was demonstrated by
adequate separation of all potential pralatrexate related substances from pralatrexate stressed drug
product samples.

Conclusion:
The developed stability indicating HPLC method was found to be suitable for the simultaneous
quantitative determination of potential degradation impurities and related substances of pralatrexate
and pralatrexate active in pralatrexate liquid formulation.
Synthesis of Spiro-Isoxazolidine Derivatives of Methyl α-Isocostate
Authors: Zaki Mohamed , Oukhrib Abdelouahd , Loubidi Mohammed , El Hakmaoui Ahmed , Hiebel Marie-Aude , Akssira Mohammed , Berteina-Raboin Sabine 
Published: September 2018

Background:
In recent decades, natural products are an important source of chemotherapeutics
as more than half of the effective cancer drugs can be traced to natural origins.

Objective:
Moreover, the modification of natural products is one of the most common and fruitful
approaches to obtain novel therapeutic agents in medicinal chemistry.

Method:
Continuing with a research project based on the support of Moroccan plant resources. we
report herein the use of α-isocostic acid extracted in enantiomerically pure form from Dittrichia viscosa
as a convenient starting material for the synthesis of new eudesmane derivatives.

Results:
Novel spiro derivatives with a natural scaffold were prepared. Spiro-isoxazolidine derivatives
were generated on the exocyclic double bond adjacent to the ester α,β-unsaturated function by 1,3-dipolar
cycloaddition of methyl α-isocostate 1 derived from sesquiterpenic isocostic acid, with nitrones 2.

Conclusion:
This procedure allowed us to generate enantiomerically pure spiro compounds in one
diastereoisomer form with a limited number of steps. These compounds were fully characterized by
spectroscopic methods.
Mussel-inspired Polymers: Recent Trends
Authors: Moulay Saad 
Published: September 2018

Background:A number of natural and synthetic polymers were subjected to functionalization with catechol-containing modifiers, mimicking the chemical structure of Mytilus foot proteins of marine mussel, and affording materials with specific properties that are related to their adhesion ability.Objective:This review highlights the various applications of mussel-inspired polymers, worked out within the last five years, in separation processes, hydrogels making, and biomedicals.Method and Results:Marine mussel-inspired polymers were fashioned either by direct synthesis from catechol-containing monomers or chemical modification of existing polymers. Mostly, the catechol units attached to the polymer matrixes are 3,4-dihydroxyphenyl-L-alanine and dopamine.Conclusion:Michael addition and/or Schiff base reaction between catechol-containing molecules units and polyamines afford efficient separative membranes. Hydrogel-making from catecholcontaining polymers can be easily realized via oxidation with oxidants and coordination with transition metal ions.
A Social Media Website (Supporting Our Valued Adolescents) to Support Treatment Uptake for Adolescents With Depression and/or Anxiety and Their Parents: Protocol for a Pilot Randomized Controlled Trial (Preprint)
Authors: Radovic Ana , Li Yaming , Landsittel Douglas , Stein Bradley D , Miller Elizabeth 
Published: September 2018

BACKGROUND

Few adolescents who experience depression or anxiety connect to mental health treatment. Supporting Our Valued Adolescents (SOVA) is a stakeholder-informed technology intervention that consists of 2 blog-format websites—one for adolescents and another for parents. SOVA is designed to intervene on targets, which may increase the mental health treatment uptake when adolescents with depression or anxiety are identified in primary care settings.

OBJECTIVE

This study aims to describe the protocol for a pilot randomized controlled trial designed to refine recruitment and retention strategies, document intervention fidelity and implementation outcomes, and assess changes in health beliefs and knowledge, emotional or informational support, and parent-adolescent communication quality in adolescents and their parents.

METHODS

Adolescents identified with symptoms of depression or anxiety, for which a health care provider recommends treatment, and their parents will be recruited from clinics where adolescents are seen for primary care. Adolescent-parent dyads will be randomized at 1:1 to both receive the SOVA websites and enhanced usual care or enhanced usual care alone. Baseline measures and 6-week and 3-month outcomes will be collected by Web-based self-report surveys and electronic health record review. The main pilot outcome is the 6-week study retention rate. Analyses will also assess changes in health beliefs and knowledge, emotional support, and parent-adolescent communication in both adolescents and their parents.

RESULTS

The project was funded in 2017. Recruitment commenced in April 2018 and enrollment is ongoing, with completion anticipated at the end of 2019 with subsequent plans for data analysis and publication submission in early 2020.

CONCLUSIONS

The findings of this research will inform the design of a multisite hybrid effectiveness-implementation randomized controlled trial examining the effectiveness and optimal implementation strategies for using SOVA in community primary care settings.

CLINICALTRIAL

ClinicalTrials.gov NCT03318666; https://clinicaltrials.gov/ct2/show/NCT03318666

INTERNATIONAL REGISTERED REPOR

PRR1-10.2196/12117
Cost impact of the transitional care model for hospitalized cognitively impaired older adults
Authors: Pauly Mark V , Hirschman Karen B , Hanlon Alexandra L , Huang Liming , Bowles Kathryn H , Bradway Christine , McCauley Kathleen , Naylor Mary D 
Published: September 2018

Aim:
The goal of this study was to compare postacute care costs of three care management interventions.
Materials & methods:
A total of 202 hospitalized older adults with cognitive impairment received either Augmented Standard Care, Resource Nurse Care or the Transitional Care Model. The Lin method was used to estimate costs at 30 and 180 days postindex hospital discharge.
Results:
The Transitional Care Model had significantly lower costs than the Augmented Standard Care group at both 30 (p < 0.001) and 180 days (p = 0.03) and significantly lower costs than Resource Nurse Care at 30 days (p = 0.02).
Conclusion:
These findings suggest that the Transitional Care Model can reduce both the amount of other postacute care and the total cost of care compared with alternative services for cognitively impaired older adults.
Clinicaltrials.gov
: NCT00294307.
Contracultura e transgressão: uma análise do álbum “tropicalia ou panis et circencis” (1968)
Authors: Silva Bruno Sanches Mariante , Gonçalves Jessica Yohana 
Published: September 2018

O movimento tropicalista é um exemplo significativo das manifestações culturais que marcaram a década de 1960 no Brasil. A influência mútua aproximou músicos que sentiam-se desafiados à crítica cultural do período. O presente artigo intenta mostrar a Tropicália como um movimento de contracultura que se propôs a evidenciar certas práticas e costumes conservadores da sociedade brasileira, bem como a transgredi-los. A crítica proposta no álbum vai além daquela endereçada às forças repressoras do Estado-militar, e abrangem as posturas conservadoras no âmbito musical, estético, comportamental e sexual. Lançado no ano de 1968 o disco-manifesto coletivo Tropicália ou panis et circenses, representa um novo momento na canção brasileira: a abertura explícita aos diálogos culturais. O estudo de algumas canções desse disco-manifesto é o que impulsiona esse estudo.
“O cinema falado é o grande culpado da transformação”: a chegada do cinema sonoro em Pernambuco (1930)
Authors: Nascimento Arthur Gustavo Lira do 
Published: September 2018

Com a chegada do cinema sonoro norte-americano às salas de cinema recifenses, a cinematografia local, ainda produzindo filmes silenciosos, perde seu espaço. O cinema mudo pernambucano foi então ofuscado pelas inovações técnicas e dificuldades financeiras. Visto as inúmeras reivindicações dos cineastas brasileiros, o governo de Getúlio Vargas, iniciado em 1930, vai buscar incentivar o cinema nacional através de leis e financiamentos voltados às produções brasileiras. No Recife, os cineastas locais encontraram nos curtas-metragens, documentários e filmes propagandísticos uma possibilidade de fazer cinema. Este artigo tem por finalidade discutir a chegada do cinema sonoro em Pernambuco e as transformações ocasionadas por este processo.
O perfil social dos juízes de fora da capitania de Mato Grosso (século XVIII): famílias, matrimônio e carreiras)
Authors: Almeida Gustavo Balbueno de 
Published: September 2018

As instituições político/administrativa e também a justiça no período do Antigo Regime português vem sendo alvo de estudos há pouco mais de vinte anos no que se refere aos diversos pontos do Império português, reino ou ultramar, entre os séculos XV e XIX. Um deles é o juizado de fora, cargo de justiça proeminentemente português e que foi levado para outros pontos do Império, com o objetivo de cercear a atividade das elites locais exercendo a justiça e presidindo a câmara dos vereadores. Partindo da ideia de que, além das instituições, deve-se estudar também os homens que ocuparam os mesmos cargos, o objetivo desse artigo é apresentar um perfil social dos juízes de fora da capitania do Mato Grosso. Serão analisadas informações sobre suas vidas pessoais, além do desenrolar da carreira destes após cumprirem o tempo do cargo na capitania do Mato Grosso.