Publications by authors named "Debabrata Chanda"

54 Publications

Cliv-92-Loaded Glycyrrhetinic Acid-Modified Chitosan Nanoparticles for Enhanced Hepatoprotection-Preparation, Characterization, and In Vivo Evaluation.

AAPS PharmSciTech 2021 Oct 26;22(8):259. Epub 2021 Oct 26.

Division of Bioprospection and Product Development, CSIR-Central Institute of Medicinal and Aromatic Plants, P.O.-CIMAP, Lucknow, 226015, Uttar Pradesh, India.

Cliv-92 is a mixture of three structurally similar coumarinolignoids and a proven hepatoprotective agent. Low aqueous solubility and poor bioavailability are notable hindrances for its further use. Therefore, glycyrrhetinic acid-linked chitosan nanoparticles loaded with Cliv-92 were prepared for active targeting to the liver. The nanoparticles were prepared by the ionic gelation method to avoid the use of toxic solvents/rigorous agitation. The method of preparation was optimized using a central composite design with independent variables, namely polymer: drug ratio (3:1, w/w), crosslinker concentration (0.5%), and stirring speed (750 rpm). The optimized nanoparticles had a mean particle size of 185.17 nm, a polydispersity index of 0.41, a zeta potential of 30.93 mV, and a drug loading of 16.30%. The prepared formulation showed sustained release of approximately 63% of loaded Cliv-92 over 72 h. The nanoparticles were freeze-dried for long-term storage and further characterized. The formulation was found to be biocompatible for parenteral delivery. In vivo imaging study showed that optimized nanoparticles were preferentially accumulated in the liver and successfully targeting the liver. The present study successfully demonstrated the improved pharmacokinetic properties (≈12% relative bioavailability) and efficacy profile (evidenced by in vivo and histopathological studies) of fabricated Cliv-92 nanoparticles.
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http://dx.doi.org/10.1208/s12249-021-02130-7DOI Listing
October 2021

Studies on Anion Exchange Membrane and Interface Properties by Electrochemical Impedance Spectroscopy: The Role of pH.

Membranes (Basel) 2021 Oct 10;11(10). Epub 2021 Oct 10.

State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin 150090, China.

Ion-exchange membranes (IEMs) represent a key component in various electrochemical energy conversion and storage systems. In this study, electrochemical impedance spectroscopy (EIS) was used to investigate the effects of structural changes of anion exchange membranes (AEMs) on the bulk membrane and interface properties as a function of solution pH. The variations in the physico/electrochemical properties, including ion exchange capacity, swelling degree, fixed charge density, zeta potentials as well as membrane and interface resistances of two commercial AEMs and cation exchange membranes (CEMs, as a control) were systematically investigated in different pH environments. Structural changes of the membrane surface were analyzed by Fourier transform infrared and X-ray photoelectron spectroscopy. Most notably, at high pH (pH > 10), the membrane (R) and the diffusion boundary layer resistances (R) increased for the two AEMs, whereas the electrical double layer resistance decreased simultaneously. This increase in R and R was mainly attributed to the deprotonation of the tertiary amino groups (-NRH) as a membrane functionality. Our results show that the local pH at the membrane-solution interface plays a crucial role on membrane electrochemical properties in IEM transport processes, particularly for AEMs.
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http://dx.doi.org/10.3390/membranes11100771DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8540937PMC
October 2021

Electroreduction of COto ethanol by electrochemically deposited Cu-lignin complexes on Ni foam electrodes.

Nanotechnology 2021 Nov 12;33(5). Epub 2021 Nov 12.

Department of Chemical Engineering, Indian Institute of Technology Delhi, New Delhi 110016, India.

A low cost, non-toxic and highly selective catalyst based on a Cu-lignin molecular complex is developed for COelectroreduction to ethanol. Ni foam (NF), Cu-Ni foam (Cu-NF) and Cu-lignin-Ni foam (Cu-lignin-NF) were prepared by a facile and reproducible electrochemical deposition method. The electrochemical COreduction activity of Cu-lignin-NF was found to be higher than Cu-NF. A maximum faradaic efficiency of 23.2% with current density of 22.5 mA cmwas obtained for Cu-lignin-NF at -0.80 V (versus RHE) in 0.1 M NaSOtowards ethanol production. The enhancement of catalytic performance is attributed to the growth of the number of active sites and the change of oxidation states of Cu and NF due to the presence of lignin.
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http://dx.doi.org/10.1088/1361-6528/ac302bDOI Listing
November 2021

Electrochemical nitrogen reduction: recent progress and prospects.

Chem Commun (Camb) 2021 Jul;57(60):7335-7349

Institute of Fundamental and Frontier Sciences, University of Electronic Science and Technology of China, Chengdu 610054, Sichuan, China.

Ammonia is one of the most useful chemicals for the fertilizer industry and is also promising as an important energy carrier for fuel cell application, and is currently mostly produced by the traditional Haber-Bosch process under high temperature and pressure conditions. This energy-intensive process is detrimental to the environment due to the dependence on fossil fuels and the emission of significant greenhouse gases (such as CO2). Ammonia production via the electrochemical nitrogen reduction reaction (ENRR) has been recognized as a green sustainable alternative to the Haber-Bosch process in recent years. Current ENRR research mainly focuses on the catalyst for ammonia selective production and the enhancement of faradaic efficiency at high current density; however, these have not been explored well due to the unavailability of highly efficient and cheap catalysts. Herein, this review provides information on the ENRR process along with (i) theoretical background, (ii) experimental methodology of the electrocatalytic process and (iii) computational screening of promising catalysts. The impact of active sites and defects on the activity, selectivity, and stability of the catalysts is deeply understood. Furthermore, we demonstrate the mechanistic understanding of the ENRR process on the surface of catalysts, with the aim of boosting the improvement of the ENRR activities. The ammonia detection methods are also summarized along with thorough discussion of control experiments. Finally, this review highlights prevailing problems in existing ENRR methods of ammonia production along with technical advancements proposed to address these issues and concludes with comments on opportunities and future directions of the ENRR process.
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http://dx.doi.org/10.1039/d1cc01451jDOI Listing
July 2021

Design, synthesis and broad spectrum antibreast cancer activity of diarylindoles via induction of apoptosis in aggressive breast cancer cells.

Bioorg Med Chem 2021 07 5;42:116252. Epub 2021 Jun 5.

CSIR-Central Institute of Medicinal and Aromatic Plants (CSIR-CIMAP), P.O. CIMAP, Kukrail Picnic Spot Road, Lucknow 226 015, U.P., India; Academy of Scientific and Innovative Research (AcSIR), New Delhi 110001, India. Electronic address:

Breast cancer is the second leading cause of cancer deaths in women with significant morbidity and mortality. Present study describes design, synthesis and detailed pharmacology of indole derivatives exhibiting remarkable broad spectrum antiproliferative activity against breast cancer cells. Detailed mechanistic evaluations confirmed induction of G0/G1 arrest, apoptosis induction, loss of mitochondrial integrity, enhanced ROS generation, autophagy, estrogen receptor β-transactivation and increased tubulin polymerization. In in-vivo efficacy studies in rodent model, these indole derivatives induced significant regression in mice mammary tumour on 21 days daily oral dose. Moreover, compounds 19 and 23 were safe in Swiss albino mice in safety studies. These diarylindoles may further be optimized for better efficacy.
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http://dx.doi.org/10.1016/j.bmc.2021.116252DOI Listing
July 2021

An improved synthesis of indanocine and antiproliferative activity of 2-benzylindanocine via microtubule destabilization.

Chem Biol Drug Des 2021 07 28;98(1):127-143. Epub 2021 May 28.

CSIR-Central Institute of Medicinal and Aromatic Plants (CSIR-CIMAP) P.O. CIMAP, Lucknow, India.

Indanocine, a potent anticancer investigational drug of National Cancer Institute-USA, has been much discussed in recent years. Present communication aimed at total synthesis of indanocine and its close analogues. Total synthesis was improved by double yields than previously reported yields. Some of the benzylidene and 2-benzyl derivatives with free rotation at C2 position exhibited potential cytotoxicities against various human cancer cell lines. Five such analogues exhibited potential antiproliferative effect against HCT-116 and MIA PACA-2 cell lines. Benzylindanocine 12i induced microtubule destabilization by occupying colchicine binding pocket of β-tubulin. It also exhibited anti-inflammatory activity by down-regulating IL-6 and TNF-α. In Ehrlich ascites carcinoma model, 12i reduced 78.4% of EAC tumour in Swiss albino mice at 90 mg/kg (i.p.) dose. Further, in in vivo safety studies, 12i was found to be safe to rodents up to 1,000 mg/kg dose. Concomitant anticancer and anti-inflammatory activity of benzylindanocine is distinctive, which suggests its further optimization for better efficacy and druggability.
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http://dx.doi.org/10.1111/cbdd.13857DOI Listing
July 2021

Antihypertensive Effect of a Novel Angiotensin II Receptor Blocker Fluorophenyl Benzimidazole: Contribution of cGMP, Voltage-dependent Calcium Channels, and BK Channels to Vasorelaxant Mechanisms.

Front Pharmacol 2021 30;12:611109. Epub 2021 Mar 30.

Bioprospection and Product Development Division, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, India.

The current study presents the novel angiotensin II receptor blocker fluorophenyl benzimidazole (FPD) as an antihypertensive agent in the SHR model of hypertension. We investigated the role of cGMP, voltage-dependent L-type calcium channels, and BK channels in the vasorelaxant mechanisms of FPD in the rat superior mesenteric artery. The antihypertensive effect of FPD was examined using an invasive technique measuring blood pressure in SHR animals. Using a myograph, tension measurement was completed in the superior mesenteric artery to elucidate the mechanisms of vasorelaxation involving AT1 receptors, the NO/cGMP pathway, L-type calcium channels, and BK channels. Ion flux (Ca, K) studies were conducted in aortic smooth muscle cells. Putative targets proteins were determined by docking studies. A safety evaluation of FPD was carried out using Swiss albino mice. FPD significantly decreased blood pressure in SHR. It relaxed superior mesenteric arteries in a concentration-dependent manner and significantly inhibited angiotensin II-induced contraction. The relaxation response was also mediated by an increase in tissue cGMP levels, inhibition of L-type calcium channels, and the opening of BK channels. FPD further enhanced efflux of K and inhibited Bay K8644-stimulated Ca influx in aortic smooth muscle cells and docked well in an study with the targets. It was well tolerated in the toxicity study. The present study reports the antihypertensive activity of novel AT-1 receptor blocker FPD at 50 and 100 mg kg with cGMP, L-type calcium channels, and BK channels as putative targets of vasorelaxation, and was found safe in oral toxicity.
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http://dx.doi.org/10.3389/fphar.2021.611109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042648PMC
March 2021

Inhibition of Mitogen-Activated Protein Kinase (MAPK)-Activated Protein Kinase 2 (MK2) is Protective in Pulmonary Hypertension.

Hypertension 2021 04 1;77(4):1248-1259. Epub 2021 Mar 1.

From the Division of Pharmacology (M.S., K.J., K.H.), CSIR-Central Drug Research Institute, Lucknow, India.

[Figure: see text].
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.15229DOI Listing
April 2021

Standardization of Kaempferia galanga L. rhizome and vasorelaxation effect of its key metabolite ethyl p-methoxycinnamate.

J Ethnopharmacol 2021 May 9;271:113911. Epub 2021 Feb 9.

Analytical Chemistry Department, CSIR-Central Institute of Medicinal and Aromatic Plants (CIMAP), Lucknow, 226 015, India. Electronic address:

Ethnopharmacological Relevance: Kaempferia galanga L. rhizome (KGR) is part of more than sixty-one Ayurvedic formulations and commonly known as 'Chandramula'. KGR is widely used in traditional Indian medicines to treat fever (jwar), rheumatism (Amavata), respiratory (Shwasa), hypertension (Vyanabala vaishamya) and cardiovascular disorders (Vyanavayu Dushtijanya Hrudrog). Although ethnomedicinal properties have extensively been demonstrated in traditional medicines of south-east countries i.e. China, India, Indonesia, and Malaysia, the chemico-biological validation are still lacking.

Aim Of The Study: Chemico-biological standardization with respect to its vasorelaxation potential is the main objective of the present study. To investigate the vasorelaxation potential of key phytochemical of KGR, i.e., ethyl-p-methoxycinnamate (EPMC) and to study it's the mechanism of action.

Materials And Methods: A HPLC method was developed and validated for the quality assessment of KGR using its two major phytochemicals i.e. ethyl-p-methoxycinnamate (EPMC) and ethyl cinnamate (EC) in KGR. The vasorelaxation effect of major phytochemicals of KGR was evaluated on the main mesenteric arteries isolated from male Wistar rats. Specific BKca channel blocker tetraethylammonium (TEA), receptor antagonist, nitric oxide scavenging capacity, and antioxidant potential were also evaluated for its plausible mechanism.

Results: Present validated HPLC method facilitates simultaneous quantitation of EPMC and EC faster than classical GC techniques. EPMC has shown a dose-dependent relaxation in rat main mesenteric arteries (MMA) contracted by U46619 with an E of 58.68 ± 3.31%. Similarly, in endothelium-denuded MMA rings, relaxation was also observed (E of 61.83 ± 3.38%). Moreover, relaxation response to EPMC has strongly inhibited (E 14.76 ± 2.29%) when the tissue exposed to depolarizing high K containing buffer for the contraction. The point correlation dimension (pD2) values were also significantly decreased in high K treated arterial rings compared to control. Interestingly, when MMA rings incubated with a specific BK channel blocker (TEA, 1 mM), the relaxation response to EPMC was also significantly blocked.

Conclusions: The first time this study demonstrated the chemical standardization of K. galanga rhizome and EPMC is responsible for its vasorelaxation potential as demonstrated by the endothelium-independent response mediated by Ca2+ dependent potassium channels.
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http://dx.doi.org/10.1016/j.jep.2021.113911DOI Listing
May 2021

Design, synthesis and drug resistance reversal potential of novel curcumin mimics Van D: Synergy potential of curcumin mimics.

Bioorg Chem 2021 01 4;106:104454. Epub 2020 Nov 4.

Bioprospection and Product Development Division, CSIR-Central Institute of Medicinal and Aromatic Plants, Near Kukrail Picnic Spot, P.O. CIMAP, Lucknow 226015, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.

Being crucial part of plant-based novel discovery of drug from natural resources, a study was done to explore the antibacterial potential of curcumin mimics in combination with antibiotics against multidrug resistant isolates of Pseudomonas aeruginosa. The best candidate Van D, a curcumin mimics reduced the MIC of tetracycline (TET) up to 16 folds against multidrug resistant clinical isolates. VanD further inhibited the efflux pumps as evident by ethidium bromide efflux and by in-silico docking studies. In another experiment, it was also found that Van D inhibits biofilm synthesis. This derivative kills the KG-P2, an isolate of P. aeruginosa in a time dependent manner, the post-antibiotic effect (PAE) of tetracycline was extended as well as mutant prevention concentration (MPC) of TET was also decreased. In Swiss albino mice, Van D reduced the proinflammatory cytokines concentration. In acute oral toxicity study, this derivative was well tolerated and found to be safe up to 1000 mg/kg dose. To the best of our knowledge, this is the first report on curcumin mimics as synergistic agent via inhibition of efflux pump.
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http://dx.doi.org/10.1016/j.bioorg.2020.104454DOI Listing
January 2021

Fluorinated benzylidene indanone exhibits antiproliferative activity through modulation of microtubule dynamics and antiangiogenic activity.

Eur J Pharm Sci 2020 Nov 14;154:105513. Epub 2020 Aug 14.

CSIR-Central Institute of Medicinal and Aromatic Plants (CSIR-CIMAP), Kukrail Picnic Spot Road, P.O. CIMAP, Lucknow, 226015, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, Uttar Pradesh, India. Electronic address:

The application of fluorine in drug design has been understood significantly by the medicinal chemists in recent years. Modulation of tubulin-microtubule dynamics is one of the most effective targets for cancer chemotherapeutics. A logically designed and identified lead compound, fluorinated benzylidene indanone 1 has been extensively evaluated for cancer pharmacology. It occupied colchicine binding pocket acting as microtubule destabilizer and induced a G2/M phase arrest in MCF-7 cells. Compound 1 exerted an antiangiogenic effect in MCF-7 cells by down-regulating Vascular Endothelial Growth Factor (VEGF) and Hypoxia Inducible Factor-α (HIF-α). In in-vivo efficacy in C3H/Jax mice mammary carcinoma model, benzylidene indanone 1 reduced tumour volumes by 48.2%. Further in acute oral toxicity studies compound 1 was well tolerated and safe up to 1000 mg/kg dose in Swiss albino mice. The fluorinated benzylidene indanone 1, a new chemical entity (NCE) can further be optimized for better efficacy against breast adenocarcinoma..
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http://dx.doi.org/10.1016/j.ejps.2020.105513DOI Listing
November 2020

Antiproliferative activity of diarylnaphthylpyrrolidine derivative via dual target inhibition.

Eur J Med Chem 2020 Feb 20;188:111986. Epub 2019 Dec 20.

CSIR-Central Institute of Medicinal and Aromatic Plants (CSIR-CIMAP), P.O. CIMAP, Kukrail Picnic Spot Road, Lucknow, 226 015, Uttar Pradesh, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, Uttar Pradesh, India. Electronic address:

Breast cancer is the second leading cause of deaths in women globally. Present communication deals with design and synthesis of a few diarylnaphthyls as possible anti-breast cancer agents. Among the thirty three representatives with significant antiproliferative activity compounds 23 and 50 were quite efficacious against human breast cancer cells. Compound 50 induced apoptosis in both MCF-7 and MDA-MB-231 cells and exerted S phase and G2/M phase arrest respectively via distinct mechanistic pathways. It showed moderate microtubule destabilization. Further, it exhibited DNA topoisomerase-II inhibition effect in MCF-7 cells. It was well tolerable and found safe up to 300 mg/kg dose in Swiss albino mice. The dual action antiproliferative effect of compound 50 is quite interesting and warrants for future development.
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http://dx.doi.org/10.1016/j.ejmech.2019.111986DOI Listing
February 2020

Synthesis and evaluation of substituted 8,8-dimethyl-8H-pyrano[2,3-f]chromen-2-one derivatives as vasorelaxing agents.

Bioorg Med Chem Lett 2020 01 28;30(1):126759. Epub 2019 Oct 28.

Medicinal Chemistry Department, CSIR-Central Institute of Medicinal and Aromatic Plants, P.O. CIMAP, Kukrail Road, Lucknow 226015, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh 201002, India. Electronic address:

A series of substituted 8,8-dimethyl-8H-pyrano[2,3-f]chromen-2-ones (chromeno-coumarin hybrids) was synthesized from scopoletin (11) as vasorelaxing agents. The synthesized compounds 21a-f, 22, 23a-e and scopoletin (11) were evaluated for vasorelaxation in endothelium intact rat main mesenteric artery (MMA). Compounds 11, 21a, 21c-f and 22 showed significant vasorelaxation in precontracted MMA within the range of EC value 1.58-5.02 µM. These derivatives presented 29.40-70.89 fold increased sensitivity for experimental tissue compared to scopoletin (11), the parent molecule. Among others, 22 was found to be the most active compound which had EC 1.58 µM with 70.89 fold increased sensitivity. The mechanistic evaluation of 22 showed that it exerted vasorelaxation through Ca-activated K (BKca) channel and the effect was endothelium-independent.
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http://dx.doi.org/10.1016/j.bmcl.2019.126759DOI Listing
January 2020

Interface Engineering of an RGO/MoS/Pd 2D Heterostructure for Electrocatalytic Overall Water Splitting in Alkaline Medium.

ACS Appl Mater Interfaces 2019 Nov 29;11(45):42094-42103. Epub 2019 Oct 29.

Department of Chemical Engineering , Indian Institute of Technology Delhi , New Delhi 110016 , India.

To achieve sustainable production of H at ambient temperature, highly active and stable electrocatalysts are the key to water splitting technology commercialization for hydrogen and oxygen production to replace Pt and IrO catalysts. Herein, a modified interface of palladium (Pd) and reduced graphene oxide (RGO)-supported molybdenum disulfide (MoS) prepared by the solvothermal followed by chemical reduction method is established, in which abundant interfaces are formed. The phase structure, composition, chemical coupling, and morphology of the two-dimensional nanostructures are established by X-ray diffraction (XRD), Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), and transmission electron microscopy, respectively. A structural phase transformation in MoS is observed from trigonal (2H) to octahedral (1T) by virtue of Pd addition, which is well established from XRD, Raman, and XPS studies. For oxygen evolution reaction (OER) and hydrogen evolution reaction (HER), the RGO/MoS/Pd (RMoSPd) catalyst exhibits extremely low overpotential (245 mV for OER and 86 mV for HER) to achieve benchmark current density, with small values of Tafel slope (42 mV dec for OER and 35.9 mV dec for HER) and charge transfer resistance. The quantitative study shows the hydrogen production rate of RMoSPd of 335 μmol h with excellent stability in alkaline medium, which is superior to MoS, RMoS, and MoSPd. The improved performance of RMoSPd is attributed to the combined synergetic effect of 1T MoS, sulfur vacancy, and conducting RGO sheet, which efficiently accelerate the overall electrochemical water splitting.
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http://dx.doi.org/10.1021/acsami.9b13358DOI Listing
November 2019

Brevifoliol ester induces apoptosis in prostate cancer cells by activation of caspase pathway.

Chem Biol Drug Des 2020 01 20;95(1):150-161. Epub 2019 Oct 20.

CSIR-Central Institute of Medicinal and Aromatics Plants (CSIR-CIMAP), Lucknow, Uttar Pradesh, India.

Prostate cancer is fourth most abundant cancer type around the globe. Brevifoliol, a rearranged taxoid from Taxus walllichiana needles has been derivatized as C5 esters using Steglich esterification reaction. Seventeen diverse analogues were evaluated against a panel of human cancer cell lines by MTT assay. Among these, two of the semi-synthetic analogues, that is, 13 and 16 exhibited potent cytotoxicity, selectively against PC-3, prostate cancer cell lines. In cell cycle analysis, analogue 13 induced S and G2/M phase arrest and induced apoptosis by activating caspase-3. Compound 13 showed moderate efficacy in in-vivo Ehrlich ascites carcinoma in Swiss albino mice. Further, compound 13 was found to be safe in Swiss albino mice up to 1,000 mg/kg dose in acute oral toxicity. Brevifoliol ester 13 may further be optimized for better efficacy.
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http://dx.doi.org/10.1111/cbdd.13631DOI Listing
January 2020

Bivalent furostene carbamates as antiproliferative and antiinflammatory agents.

J Steroid Biochem Mol Biol 2019 11 24;194:105457. Epub 2019 Aug 24.

CSIR-Central Institute of Medicinal and Aromatic Plants (CSIR-CIMAP), P.O. CIMAP, Kukrail Picnic Spot Road, Lucknow, 226 015, Uttar Pradesh, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, Uttar Pradesh, India. Electronic address:

Breast cancer is the most prevalent cancer in women affecting about 12% of world's female population. It is a multifactorial disease, mostly invasive in nature. Diosgenin and related compounds are potent antiproliferative agents. Carbamate derivatives have been synthesized at C26 of furostene ring after opening spiroketal bond (F-ring) of diosgenin. Compound 10 possessed significant antiproliferative activity against human breast cancer cells by arresting the population at G1 phase of cell division cycle and induced apoptosis. Induction of apoptosis was observed through the caspase signalling cascade by activating caspase-3. Moreover, carbamate 10 exhibited moderate antiinflammatory activity by decreasing the expression of cytokines, TNF-α and IL-6 in LPS-induced inflammation in primary macrophage cells. Furthermore, compound 10 significantly reduced Ehrlich ascites carcinoma significantly in mice. It was well tolerated and safe in acute oral toxicity in Swiss albino mice. The concomitant anticancer and antiinflammatory properties of carbamate 10 are important and thus, can further be optimized for a better anti-breast cancer candidate.
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http://dx.doi.org/10.1016/j.jsbmb.2019.105457DOI Listing
November 2019

Antihypertensive activity of diethyl-4,4'-dihydroxy-8,3'-neolign-7,7'-dien-9,9'-dionate: A continuation study in L-NAME treated wistar rats.

Eur J Pharmacol 2019 Sep 21;858:172482. Epub 2019 Jun 21.

Molecular Bioprospection Department, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, 226015, India. Electronic address:

In the present study, we report that neolignan1 (Diethyl-4,4'-dihydroxy-8,3'-neolign-7,7'-dien-9,9'-dionate) relaxes the superior mesenteric artery in a concentration dependent manner (pD2 value 5.392 ± 0.04; n = 8 for endothelium intact and 5.204 ± 0.03; n = 8 for endothelium denuded mesenteric rings, respectively). The relaxation response of neolignan1 was found to be endothelium independent and sensitive to 1H-[1,2,4] oxadiazolo [4,3-a]quinoxalin-1-on (ODQ; 1 μM) and tetraethyl ammonium (TEA; 1 mM). In-silico studies showed good LibDock score (92.66) of neolignan1 with BK channel and are in well corroboration with ex-vivo study. Further, neolignan1 significantly decreased the systolic blood pressure, diastolic blood pressure and mean arterial pressure in the Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME; 50 mg/kg) treated Wistar rats at the dose of 30 and 100 mg/kg given once orally for 15 days. In addition, neolignan1 is well tolerated up to 100 mg/kg when given as a repeated dose, once orally for 28 days in Swiss albino mice. Neolignan1 was well absorbed from oral route, reached peak at 4 h and eliminated below detection level by 12 h after administration. Our present study concludes that neolignan1 produced relaxation in superior mesenteric artery by opening of BK channel and produced significant antihypertensive activity in L-NAME treated Wistar rats and was well tolerated by the experimental animal.
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http://dx.doi.org/10.1016/j.ejphar.2019.172482DOI Listing
September 2019

3-Arylindanones and related compounds as antiproliferative agents against colorectal cancer.

Chem Biol Drug Des 2019 09 10;94(3):1694-1705. Epub 2019 Jul 10.

CSIR-Central Institute of Medicinal and Aromatic Plants (CSIR-CIMAP), Lucknow, India.

Diverse benzylidene indanones and their derivatives were synthesized as anticancer agents. Two of the analogues, that is 7 and 22, exhibited significant antiproliferative activity against several human cancer cell lines. Both the compounds possessed antimitotic activity and induced apoptosis in DLD1 colorectal adenocarcinoma cells through activation of caspase pathways. In cell cycle analysis, both the compounds induced predominantly G2/M phase arrest in DLD1 cells. Molecular docking studies revealed that compound 7 occupies colchicine binding pocket of β-tubulin. Both the compounds were safe in acute oral toxicity in rodents. Both the compounds are further being optimized for better efficacy.
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http://dx.doi.org/10.1111/cbdd.13574DOI Listing
September 2019

A novel synthesis of 2-arylbenzimidazoles in molecular sieves-MeOH system and their antitubercular activity.

Bioorg Med Chem 2018 08 1;26(15):4551-4559. Epub 2018 Aug 1.

CSIR-Central Institute of Medicinal and Aromatic Plants (CSIR-CIMAP), P.O. CIMAP, Kukrail Picnic Spot Road, Lucknow 226 015, U.P., India. Electronic address:

Arylbenzimidazoles have been synthesized as antimycobacterial agents. An efficient synthesis has been developed for 2-arylbenzimidazoles from o-phenylenediamines and aromatic aldehydes in molecular sieves-methanol system. The methodology is straightforward to get 2-arylbenzimidazoles (3a-3z) in excellent yields with high chemoselectivity over 2-aryl-1-benzylbenzimidazoles (4a-4z). All these benzimidazole analogues were evaluated against M. tuberculosis in BACTEC radiometric assay. The compounds 4y and 4z exhibited potential antitubercular activity against M. tuberculosis HR, MIC at 16 µM and 24 µM respectively. The best compound of the series i.e. compound 4y was well tolerated by Swiss-albino mice in acute oral toxicity. Compound 4y possessing a diarylbenzimidazole core, can further be optimized for better activity.
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http://dx.doi.org/10.1016/j.bmc.2018.07.049DOI Listing
August 2018

Antiproliferative efficacy of curcumin mimics through microtubule destabilization.

Eur J Med Chem 2018 May 26;151:51-61. Epub 2018 Mar 26.

CSIR-Central Institute of Medicinal and Aromatic Plants (CSIR-CIMAP), Kukrail Picnic Spot Road, P.O. CIMAP, Lucknow, 226015, India. Electronic address:

Curcumin possesses an attractive chemical structure with highly conjugated diferuloylmethane core. Curcumin mimics have been designed and prepared with an additional bridged phenyl ring in conjugation. Fourteen diverse analogues were evaluated against a panel of human cancer cell lines. The best analogue of the series i.e. compound 6a exhibited potent cytotoxicity against A431, epidermoid carcinoma cell line (IC = 1.5 μM) and DLD1, colorectal adenocarcinoma cell line (IC = 6.9 μM). In tubulin kinetics experiment, compound 6a destabilized polymerisation process (IC = 4.68 μM). In cell cycle analysis, compound 6a exerted G2/M phase arrest in A431 cells and induced apoptosis. In Ehrlich Ascites Carcinoma in Swiss-albino mice, compound 6a showed 78.6% tumour reduction at 80 mg/kg dose and 57% solid tumour reduction at 150 mg/kg dose. Further, in acute-oral toxicity experiment in rodent model, compound 6a was given in three different oral doses to Swiss albino mice. There were non-significant changes in various biochemical parameters and major body organs studied, including their absolute and relative weights. It was tolerable up to 300 mg/kg dose in Swiss-albino mice. The present study shows that the novel curcumin mimic 6a is a safe and efficacious anticancer compound. However, it needs to be optimized for better efficacy.
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http://dx.doi.org/10.1016/j.ejmech.2018.03.063DOI Listing
May 2018

Essential oil from waste leaves of Curcuma longa L. alleviates skin inflammation.

Inflammopharmacology 2018 Oct 10;26(5):1245-1255. Epub 2018 Feb 10.

Molecular Bioprospection Department, CSIR-Central Institute of Medicinal and Aromatic Plants (CIMAP), PO CIMAP, Lucknow, 226015, India.

Background: Curcuma longa L. is an important industrial crop used by medicinal and cosmetic industries in the world. Its leaves are a waste material after harvesting rhizomes. The aim of the study was to evaluate the chemical and pharmacological profile of essential oil from waste leaves of Curcuma longa (EOCl) against skin inflammation.

Methods: EOCl was subjected to gas chromatography (GC) analysis for identification of essential oil constituents and its anti-inflammatory evaluation through in vitro and in vivo models.

Results: Chemical fingerprinting using GC and GC-MS analysis of EOCl revealed the presence of 11 compounds, representing 90.29% of the oil, in which terpinolene (52.88%) and α-phellandrene (21.13%) are the major components. In the in vitro testing EOCl inhibited the production of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) in lipopolysaccharide (LPS) and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation in the human keratinocyte cell line (HaCaT). Topical application of EOCl produced anti-inflammatory effects by reducing ear thickness, ear weight and ameliorating the level of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) at protein and mRNA levels as well as regulating the overproduction of oxidative markers and restoring the histopathological damage in a TPA-induced mouse model of inflammation.

Conclusion: These findings of topical anti-inflammatory properties of EOCl provide a scientific basis for medicinal use of this plant material against inflammatory disorders.
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http://dx.doi.org/10.1007/s10787-018-0447-3DOI Listing
October 2018

Chemical Composition and Allelopathic, Antibacterial, Antifungal, and Antiacetylcholinesterase Activity of Fish-mint (Houttuynia cordataThunb.) from India.

Chem Biodivers 2017 Oct 21;14(10). Epub 2017 Sep 21.

CSIR-Central Institute of Medicinal and Aromatic Plants, PO CIMAP, Near Kukrail Picnic Spot, Lucknow-226015, Uttar Pradesh, India.

Fish-mint (Houttuynia cordataThunb.), belonging to family Saururaceae, has long been used as food and traditional herbal medicine. The present study was framed to assess the changes occurring in the essential-oil composition of H. cordata during annual growth and to evaluate allelopathic, antibacterial, antifungal, and antiacetylcholinesterase activities. The essential-oil content ranged from 0.06 - 0.14% and 0.08 - 0.16% in aerial parts and underground stem, respectively. The essential oils were analysed by GC-FID, GC/MS, and NMR ( H and C). Major constituents of aerial-parts oil was 2-undecanone (19.4 - 56.3%), myrcene (2.6 - 44.3%), ethyl decanoate (0.0 - 10.6%), ethyl dodecanoate (1.1 - 8.6%), 2-tridecanone (0.5 - 8.3%), and decanal (1.1 - 6.9%). However, major constituents of underground-stem oil were 2-undecanone (29.5 - 42.3%), myrcene (14.4 - 20.8%), sabinene (6.0 - 11.1%), 2-tridecanone (1.8 - 10.5%), β-pinene (5.3 - 10.0%), and ethyl dodecanoate (0.8 - 7.3%). Cluster analysis revealed that essential-oil composition varied substantially due to the plant parts and season of collection. The oils exhibited significant allelopathic (inhibition: 77.8 - 88.8%; LD : 2.45 - 3.05 μl/plate), antibacterial (MIC: 0.52 - 2.08 μl/ml; MBC: bacteriostatic) and antifungal (MIC: 2.08 - 33.33 μl/ml; MFC: 4.16 - 33.33 μl/ml) activities. The results indicate that the essential oil from H. cordata has a significant potential to allow future exploration and exploitation as a natural antimicrobial and allelopathic agent.
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http://dx.doi.org/10.1002/cbdv.201700189DOI Listing
October 2017

Chemical composition and antibacterial, antifungal, allelopathic and acetylcholinesterase inhibitory activities of cassumunar-ginger.

J Sci Food Agric 2018 Jan 24;98(1):321-327. Epub 2017 Jul 24.

Botanical Survey of India-APRC, Senki View, Itanagar, Arunachal Pradesh, India.

Background: Zingiber montanum (J.Koenig) Link ex A.Dietr. (Zingiberaceae), commonly known as cassumunar-ginger, is a folk remedy for the treatment of inflammations, sprains, rheumatism and asthma. The aim of the present study was to assess the chemical composition, and antibacterial, antifungal, allelopathic and acetylcholinesterase inhibitory activities of the essential oil of Z. montanum originating from India.

Results: The hydrodistilled essential oil of Z. montanum rhizome was analyzed using gas chromatography-flame ionization detection and gas chromatography-mass spectrometry. A total of 49 constituents, forming 98.7-99.9% of the total oil compositions, was identified. The essential oil was characterized by higher amount of monoterpene hydrocarbons (32.6-43.5%), phenylbutanoids (27.5-41.2%) and oxygenated monoterpenes (11.4-34.1%). Major constituents of the oil were sabinene (13.5-38.0%), (E)-1-(3',4'-dimethoxyphenyl)buta-1,3-diene (DMPBD) (20.6-35.3%), terpinen-4-ol (9.0-31.3%), γ-terpinene (1.1-4.8%) and β-phellandrene (1.0-4.4%). The oil was evaluated against eight pathogenic bacteria and two fungal strains. It exhibited low to good antibacterial activity (minimum inhibitory concentration: 125-500 µg mL ) and moderate antifungal activity (250 µg mL ) against the tested strains. The oil reduced germination (69.8%) and inhibited the root and shoot growth of lettuce significantly (LD : 3.58 µL plate ). However, it did not demonstrate acetylcholinesterase inhibitory activity up to a concentration of 10 mg mL .

Conclusions: The essential oil of Z. montanum can be used as a potential source of DMPBD, terpinen-4-ol and sabinene for pharmaceutical products. The results of the present study add significant information to the pharmacological activity of Z. montanum native to India. © 2017 Society of Chemical Industry.
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http://dx.doi.org/10.1002/jsfa.8474DOI Listing
January 2018

Diethyl-4,4'-dihydroxy-8,3'-neolign-7,7'-dien-9,9'-dionate exhibits antihypertensive activity in rats through increase in intracellular cGMP level and blockade of calcium channels.

Eur J Pharmacol 2017 Mar 31;799:84-93. Epub 2017 Jan 31.

Molecular Bioprospection Department, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow 226015, India. Electronic address:

We report here the antihypertensive and vasorelaxant potential of some steroidal and non-steroidal compounds identified through a library of compounds. All the novel analogues showed vasorelaxant potential in isolated rat aorta. The most potent lead neolignan1 (Diethyl-4,4'-dihydroxy-8,3'-neolign-7,7'-dien-9,9'-dionate) produced concentration dependent relaxation with [pD 5.16±0.05; n=16 and E 96.97%±1.12%; n=16]. The neolignan1 relaxation is independent of endothelium and is sensitive to ODQ (1H-[1, 2, 4] oxadiazolo [4, 3-a] quinoxalin-1-one; a blocker of soluble guanylyl cyclase (sGC) which synthesizes cGMP (cyclic guanosine monophosphate)). ELISA analysis of treated arterial tissues showed concentration-dependent increase in cGMP level in treated tissues compared to control (2.03 and 7.16 fold of control at 10 and 30µM of neolignan1, respectively) and a synergistic increase in cGMP level by 26.66 fold compared to control when used in combination with sildenafil (10µM; a known inducer of cGMP level by selectively blocking cGMP specific phosphodiesterase 5). Our present study reports for the first time that neolignans produce relaxation in isolated rat aorta through increase in intracellular cGMP level. The ODQ resistant relaxation of neolignan1 is mediated by blockade of voltage dependent L-type calcium channel (VDCC) as observed in the experiment with CaCl. Neolignan1 upon intravenous administration via tail vein in Spontaneously Hypertensive Rats (SHR) produced significant decrease in systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial blood pressure (MAP). The present study concludes that neolignan1 exhibited antihypertensive potential in rats through rise in intracellular cGMP and blockade of VDCC.
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http://dx.doi.org/10.1016/j.ejphar.2017.01.044DOI Listing
March 2017

(22β,25R)-3β-Hydroxy-spirost-5-en-7-iminoxy-heptanoic acid exhibits anti-prostate cancer activity through caspase pathway.

Steroids 2017 03 28;119:43-52. Epub 2017 Jan 28.

CSIR-Central Institute of Medicinal and Aromatic Plants (CSIR-CIMAP), Kukrail Picnic Spot Road, P.O. CIMAP, Lucknow 226015, India. Electronic address:

Prostate cancer is one of the most common cancers in men. Diosgenin and related compounds are potential cytotoxic agents. Twelve diverse analogues of long chain fatty acid/ester of diosgenin-7-ketoxime have been prepared. Six of the analogues exhibited significant anticancer activity against a panel of human cancer cell lines with IC ranging from 12 to 35μM. Compound 16, the best representative of the series exerted S phase arrest in DU145 prostate cancer cells and induced apoptosis through caspase pathway. Additionally, these analogues inhibited lipopolysaccharide induced pro-inflammatory cytokines (TNF-α and IL-6) up to 47.7% and 23.3% respectively. Compound 16 was found to be safe in acute oral toxicity in Swiss albino mice up to 300mg/kg dose. The anticancer and antiinflammatory properties of compound 16 are important and can further be optimized for a better anti-prostate cancer candidate.
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http://dx.doi.org/10.1016/j.steroids.2017.01.001DOI Listing
March 2017

Synthesis of pharmacologically important naphthoquinones and anticancer activity of 2-benzyllawsone through DNA topoisomerase-II inhibition.

Bioorg Med Chem 2017 02 28;25(4):1364-1373. Epub 2016 Dec 28.

CSIR-Central Institute of Medicinal and Aromatic Plants (CSIR-CIMAP), Lucknow 226015, U.P., India. Electronic address:

Naphthoquinones are naturally occurring biologically active entities. Practical de novo syntheses of three naphthoquinones i.e. lawsone (1), lapachol (2), and β-lapachone (3b) have been achieved from commercially available starting materials. The conversion of lapachol (2) to β-lapachone (3b) was achieved through p-TSA/Iodine/BF-etherate mediated regioselective cyclisation. Further, 2-alkyl and 2-benzyllawsone derivatives have been prepared as possible anticancer agents. Four derivatives exhibited significant anticancer activity and the best analogue i.e. compound 21a exhibited potential anticancer activity (IC=5.2μM) against FaDu cell line. Compound 21a induced apoptosis through activation of caspase pathway and exerted cell cycle arrest at S phase in FaDU cells. It also exhibited significant topoisomerase-II inhibition activity. Compound 21a was found to be safe in Swiss albino mice up to 1000mg/kg oral dose.
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http://dx.doi.org/10.1016/j.bmc.2016.12.043DOI Listing
February 2017

Anticancer activity of gallic acid template-based benzylidene indanone derivative as microtubule destabilizer.

Chem Biol Drug Des 2016 11 6;88(5):625-634. Epub 2016 Aug 6.

CSIR-Central Institute of Medicinal and Aromatic Plants (CSIR-CIMAP), Lucknow, Uttar Pradesh, India.

Benzylidene indanones have been designed and synthesized from gallic acid, a plant phenolic acid as possible anticancer agent. The best analogue of the series, that is, 3-(3',4',5'-trimethoxyphenyl)-4,5,6-trimethoxy-2-(4˝-nitrobenzylidene)-indan-1-one (8) exhibited potent cytotoxicity (IC =3-10 μm) against several human cancer cell lines through microtubule destabilization (IC =1.54 μm) after occupying colchicine-binding site of β-tubulin. In cell cycle analysis, compound 8 exerted G2/M phase arrest in both MCF-7 and MDA-MB-231 cells and induced apoptosis. It reduced 34.8% solid tumor in in vivo Ehrlich ascite carcinoma in Swiss albino mice at 30 mg/kg dose. In acute oral toxicity experiment, it was tolerable up to 300 mg/kg doses in Swiss albino mice. The lead compound 8 needs to be optimized for better activity.
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http://dx.doi.org/10.1111/cbdd.12805DOI Listing
November 2016

Differentiation of skeletal osteogenic progenitor cells to osteoblasts with 3,4-diarylbenzopyran based amide derivatives: Novel osteogenic agents.

Eur J Med Chem 2016 Oct 9;121:82-99. Epub 2016 May 9.

Division of Endocrinology, CSIR-Central Drug Research Institute, Sector-10, Jankipuram Extension, Lucknow, 226031, India.

A series of 3,4-diarylbenzopyran based amide derivatives was synthesized and evaluated for osteogenic activity in in vitro and in vivo models of osteoporosis. Compounds 17a, 21b-c and 22a-b showed significant osteogenic activity in osteoblast differentiation assay. Among the synthesized compounds, 22b was identified as lead molecule which showed significant osteogenic activity at 1 pM concentration in osteoblast differentiation assay and at 1 mg kg(-1) body weight dose in estrogen deficient balb/c mice model. In vitro bone mineralization and expression of osteogenic marker genes viz BMP-2, RUNX-2, OCN, and collagen type 1 further confirmed the osteogenic potential of 22b. Gene expression study for estrogen receptor α and β (ER-α and ER-β) in mouse calvarial osteoblasts (MCOs) unveiled that possibly 22b exerted osteogenic efficacy via activation of Estrogen receptor-β preferentially. In vivo pharmacokinetic, estrogenicity and acute toxicity studies of 22b showed that it had good bioavailability and was devoid of uterine estrogenicity at 1 mg kg(-1) and inherent toxicity up to 1000 mg kg(-1) body weight dose respectively.
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http://dx.doi.org/10.1016/j.ejmech.2016.05.023DOI Listing
October 2016

Development, optimization, and characterization of a novel tea tree oil nanogel using response surface methodology.

Drug Dev Ind Pharm 2016 Sep 15;42(9):1434-45. Epub 2016 Feb 15.

a Department of Herbal Medicinal Products , CSIR - Central Institute of Medicinal and Aromatic Plants, PO CIMAP , Lucknow , UP , India ;

Purpose: To develop and optimize nanoemulsion (NE)-based emulgel (EG) formulation as a potential vehicle for topical delivery of tea tree oil (TTO).

Methodology: Central composite design was adopted for optimizing the processing conditions for NE preparation by high energy emulsification method viz. surfactant concentration, co-surfactant concentration, and stirring speed. The optimized NE was developed into emulgel (EG) using pH sensitive polymer Carbopol 940 and triethanolamine as alkalizer. The prepared EG was evaluated for its pH, viscosity, and texture parameters, ex vivo permeation at 37 °C and stability. Antimicrobial evaluation of EG in comparison to conventional gel and pure TTO was also carried out against selected microbial strains.

Results And Discussion: Optimized NE had particle size and zeta potential of 16.23 ± 0.411 nm and 36.11 ± 1.234 mV, respectively. TEM analysis revealed the spherical shape of droplets. The pH of EG (5.57 ± 0.05 ) was found to be in accordance with the range of human skin pH. EG also illustrated efficient permeation (79.58 μL/cm(2)) and flux value (JSS) of 7.96 μL cm(2)/h through skin in 10 h. Viscosity and texture parameters, firmness (9.3 ± 0.08 g), spreadability (2.26 ± 0.06 mJ), extrudability (61.6 ± 0.05 mJ), and adhesiveness (8.66 ± 0.08 g) depict its suitability for topical application. Antimicrobial evaluation of EG with same amount of TTO as conventional gel revealed broader zones of growth inhibitions against all the selected microbial strains. Moreover, EG was also found to be nonirritant (PII 0.0833). These parameters were consistent over 90 d.

Conclusion: TTO EG turned out to be a promising vehicle for the topical delivery of TTO with enhanced therapeutic efficacy.
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http://dx.doi.org/10.3109/03639045.2016.1141931DOI Listing
September 2016
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