Publications by authors named "Kuladip Jana"

74 Publications

Filarial thioredoxin reductase exerts anti-inflammatory effects upon lipopolysaccharide induced inflammation in macrophages.

Int J Biol Macromol 2021 Nov 10. Epub 2021 Nov 10.

Parasitology Laboratory, Department of Zoology, Siksha Bhavana, Visva-Bharati, Santiniketan 731235, India. Electronic address:

Lymphatic filariasis and its associated health hazards have taken enormous tolls especially in the tropical and sub-tropical countries round the globe. Our present work contemplates the immunomodulatory role of filarial Thioredoxin reductase (TrxR) for the survival of the parasite inside the human host. For this, the protein TrxR was purified from the filarial parasite Setaria cervi and further substantiated through specific anti-TrxR antibody raised in mice. Both commercially available anti-TrxR antibody and laboratory raised antibody produced a single band with a molecular mass of ~80 kDa on western blot. The protein is optimally active at pH 7.0 and at temperature 37 °C. This protein contains both alpha helix and beta pleated sheet with selenocysteine at its active site. The Km was found to be 2.75 ± 0.49 mM. TrxR was found to downregulate lipopolysaccharide (LPS)-induced inflammation in macrophages due to inhibition of TLR4-NF-κB pathway. The result was further supported by the downregulation of inflammasome pathway and activation of alternatively activated macrophages upon TrxR treatment. Hence this study projects insights into the importance of filarial TrxR in host-parasite interface as well as it illustrates novel therapeutic strategy towards anti-filarial drug development.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.10.200DOI Listing
November 2021

Cloning and immunobiochemical analyses on recombinant chymopapain allergen Cari p 2 showing pollen-fruit cross-reaction.

Mol Immunol 2021 09 29;137:42-51. Epub 2021 Jun 29.

Division of Plant Biology (Main campus), Bose Institute, 93/1 Acharya Prafulla Chandra Road, Kolkata, 700009, West Bengal, India. Electronic address:

Papaya is reported to trigger food and respiratory allergy. Here, we identified chymopapain Cari p 2 as an allergen that can sensitize atopic individuals through fruit consumption followed by respiratory hazards through pollen exposure. Recombinant Cari p 2 displayed IgE-reactivity with 78% of papaya allergic sera. rCari p 2 also displayed allergenic activity through basophil degranulation. rCari p 2 is correctly folded and showed irreversible denaturation in the melting curve. rCari p 2 displayed IgE-cross-reactivity with homologous cysteine proteases from kiwi and pineapple. Cari p 2 transcript was also detected in papaya pulps. rCari p 2 was resistant to pepsin digestion and retained IgE-reactivity after 60 minutes of pepsin digestion. In mouse model, rCari p 2 was found to elicit inflammatory responses in the lung and gastrointestinal epithelium. Hence, Cari p 2 is a newly characterized allergen with diagnostic and immunotherapeutic potential for managing allergic disorders in papaya sensitized individuals.
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http://dx.doi.org/10.1016/j.molimm.2021.06.010DOI Listing
September 2021

Triggering the downstream apoptotic signal inside human parasitic organisms demonstrates a promising approach for anti-parasitic drug development: A mechanistic perspective.

Adv Protein Chem Struct Biol 2021 23;125:193-213. Epub 2021 Jan 23.

Parasitology Laboratory, Department of Zoology, Siksha-Bhavana, Visva-Bharati, Santiniketan, West Bengal, India. Electronic address:

Parasitic organisms of various genera have threatened humankind. Although they are not always fatal but can damage the well-being of an individual in terms of both economic and societal crisis. Marked progress has been made toward eliminating those pathogenic organisms, however, complete removal is still not possible. Several antiparasitic drug moieties have been largely commercialized and are routinely used at the same time novel drug candidates are still required. Programmed cell death (PCD) is a vital biological phenomenon inside every organism. Particularly, induction of the death signaling inside the parasitic species through selective targeting of effective drug candidates is one of the major strategies to combat these infectious organisms. In this chapter significance of apoptosis induction to eliminate the parasitic disease has been illustrated with suitable references. Moreover, we have shared our own experiences of apoptosis induction in eliminating a World Health Organization enlisted Neglected Tropical Disease, lymphatic filariasis. On the other hand, we have also tried to put some light on the mechanism of apoptosis in different parasites.
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http://dx.doi.org/10.1016/bs.apcsb.2020.12.002DOI Listing
September 2021

Disruption of redox homeostasis with synchronized activation of apoptosis highlights the antifilarial efficacy of novel piperine derivatives: An in vitro mechanistic approach.

Free Radic Biol Med 2021 06 23;169:343-360. Epub 2021 Apr 23.

Parasitology Laboratory, Department of Zoology, Siksha-Bhavana, Visva-Bharati, Santiniketan, 731235, West Bengal, India. Electronic address:

A series of novel piperine derivatives were synthesized with high yield and were evaluated for its antifilarial potential against the bovine filarial parasite Setaria cervi. Among 21 (3a-3u) compounds screened, three of them (3k, 3l, 3s) showed significant potential against all the developmental stages (oocytes, microfilariae and adult) of the filarial worm in time and dose dependent manner. 3l showed the highest efficacy among the selected three compounds. These three compounds were further evaluated for both in vitro and in vivo toxicity analyses which further fortified the benign nature of the selected compounds. The antifilarial activities they exhibited were clearly fuelled through disparity of the internal redox homeostasis as evidenced from the alterations in the enzymatic and non-enzymatic antioxidants level which ultimately shifted towards activation of pro-apoptotic signaling cascade eventually leading to the death of the parasites. The ability of the compound 3l to bind thioredoxin reductase and CED-3 protein are the key findings of this study. The present study supported with several biological experiments is therefore a maiden report on the antifilarial effectiveness of these novel piperine derivatives.
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http://dx.doi.org/10.1016/j.freeradbiomed.2021.04.026DOI Listing
June 2021

Leishmania donovani Targets Host Transcription Factor NRF2 To Activate Antioxidant Enzyme HO-1 and Transcriptional Repressor ATF3 for Establishing Infection.

Infect Immun 2021 06 16;89(7):e0076420. Epub 2021 Jun 16.

Department of Biochemistry, University of Calcutta, Kolkata, India.

We showed previously that antioxidant enzyme heme oxygenase 1 (HO-1) is critical for survival in visceral leishmaniasis. HO-1 inhibits host oxidative burst and inflammatory cytokine production, leading to parasite persistence. In the present study, screening of reported HO-1 transcription factors revealed that infection upregulated (4.1-fold compared to control [ < 0.001]) nuclear factor erythroid 2 (NFE2)-related factor 2 (NRF2). Silencing of NRF2 reduced both HO-1 expression and parasite survival. Investigation revealed that infection-induced transient reactive oxygen species (ROS) production dissociated NRF2 from its inhibitor KEAP1 and enabled phosphorylation-dependent nuclear translocation. Both NRF2 and HO-1 silencing in infection increased production of proinflammatory cytokines. But the level was greater in NRF2-silenced cells than in HO-1-silenced ones, suggesting the presence of other targets of NRF2. Another stress responsive transcription factor ATF3 is also induced (4.6-fold compared to control [ < 0.001]) by NRF2 during infection. Silencing of ATF3 reduced parasite survival (59.3% decrease compared to control [ < 0.001]) and increased proinflammatory cytokines. Infection-induced ATF3 recruited HDAC1 into the promoter sites of tumor necrosis factor alpha (TNF-α) and interleukin 12b (IL-12b) genes. Resulting deacetylated histones prevented NF-κB promoter binding, thereby reducing transcription of inflammatory cytokines. Administering the NRF2 inhibitor trigonelline hydrochloride to infected BALB/c mice resulted in reduced HO-1 and ATF3 expression, decreased spleen and liver parasite burdens, and increased proinflammatory cytokine levels. These results suggest that upregulates NRF2 to activate both HO-1 and ATF3 for disease progression.
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http://dx.doi.org/10.1128/IAI.00764-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8373246PMC
June 2021

Corrigendum to "Natural product inspired allicin analogs as novel anti-cancer agents" [Bioorg. Chem. 86 (2019) 259-272].

Bioorg Chem 2021 May 5;110:104780. Epub 2021 Mar 5.

Bose Institute, Division of Molecular Medicine, P-1/12, C.I.T. Scheme VII M, Kolkata 700054, India. Electronic address:

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http://dx.doi.org/10.1016/j.bioorg.2021.104780DOI Listing
May 2021

Identification and biochemical characterization of Asp t 36, a new fungal allergen from Aspergillus terreus.

J Biol Chem 2020 12;295(51):17852-17864

Division of Plant Biology, Bose Institute (Main Campus), Kolkata, India. Electronic address:

Aspergillus terreus is an allergenic fungus, in addition to causing infections in both humans and plants. However, the allergens in this fungus are still unknown, limiting the development of diagnostic and therapeutic strategies. We used a proteomic approach to search for allergens, identifying 16 allergens based on two-dimensional immunoblotting with A. terreus susceptible patient sera. We further characterized triose-phosphate isomerase (Asp t 36), one of the dominant IgE (IgE)-reactive proteins. The gene was cloned and expressed in Escherichia coli. Phylogenetic analysis showed Asp t 36 to be highly conserved with close similarity to the triose-phosphate isomerase protein sequence from Dermatophagoides farinae, an allergenic dust mite. We identified four immunodominant epitopes using synthetic peptides, and mapped them on a homology-based model of the tertiary structure of Asp t 36. Among these, two were found to create a continuous surface patch on the 3D structure, rendering it an IgE-binding hotspot. Biophysical analysis indicated that Asp t 36 shows similar secondary structure content and temperature sensitivity with other reported triose-phosphate isomerase allergens. In vivo studies using a murine model displayed that the recombinant Asp t 36 was able to stimulate airway inflammation, as demonstrated by an influx of eosinophils, goblet cell hyperplasia, elevated serum Igs, and induction of Th2 cytokines. Collectively, our results reveal the immunogenic property of Asp t 36, a major allergen from A. terreus, and define a new fungal allergen more broadly. This allergen could serve as a potent candidate for investigating component resolved diagnosis and immunotherapy.
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http://dx.doi.org/10.1074/jbc.RA120.015801DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762961PMC
December 2020

Corrigendum to "Anti-cancer potential of (1,2-dihydronaphtho[2,1-b]furan-2-yl)methanone derivatives" [Bioorg. Med. Chem. Lett. 30 (2020) 127476].

Bioorg Med Chem Lett 2021 Feb 2;34:127764. Epub 2021 Jan 2.

Bose Institute, Division of Molecular Medicine, P-1/12, C.I.T. Scheme VII M, Kolkata 700054, India. Electronic address:

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http://dx.doi.org/10.1016/j.bmcl.2020.127764DOI Listing
February 2021

X-ray structure of two Schiff bases: TURN-ON sensing of Fe and Al in the HepG2 cell line.

Anal Methods 2020 12 5;12(45):5485-5495. Epub 2020 Nov 5.

Department of Chemistry, Jadavpur University, Kolkata-700032, India.

The efficiency of the fluorescence sensitivity of a sensor may be tuned by the modulation of the steric and electronic parameters in the structure. In this study, the thiophenyl Schiff base (E)-N-(phenyl(pyridin-2-yl)methyl)-N-(thiophen-2-ylmethylene)benzene-1,2-diamine (HL') exhibited very high selectivity and a sensitive fluorescence enhancement towards Fe with violet emission (λ, 385 nm; LOD, 3.8 nM). On the other hand, the naphthyl Schiff base (E)-1-(((2-((phenyl(pyridin-2-yl)methyl)amino)phenyl)imino)methyl)naphthalen-2-ol (HL'') exhibited fluorescence sensitivity towards Al, showing blue emission (λ, 502 nm; LOD, 3.3 nM) in HO (HEPES buffer, pH 7.4) medium. The emission enhancement of HL' upon binding to Fe may be considered to be due to the restriction of intramolecular rotation, while the selectivity of HL'' towards Al may be due to the turn on emission through the restriction of excited state intramolecular proton transfer (ESIPT) and the introduction of chelation enhanced fluorescence (CHEF). Furthermore, DFT computation supported the sensing strategy and the probes were applied for intracellular detection of Fe and Al in HepG2 cell lines.
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http://dx.doi.org/10.1039/d0ay01090aDOI Listing
December 2020

repression by pluripotency factors and consequent chemoresistance in breast cancer stem-like cells is reversed by aspirin.

Sci Signal 2020 10 20;13(654). Epub 2020 Oct 20.

Division of Molecular Medicine, Bose Institute, P-1/12 CIT Scheme VII M, Kolkata-700 054, India.

The high abundance of drug efflux pumps in cancer stem cells (CSCs) contributes to chemotherapy resistance. The transcriptional regulator SMAR1 suppresses CSC expansion in colorectal cancer, and increased abundance of SMAR1 is associated with better prognosis. Here, we found in breast tumors that the expression of was decreased in CSCs through the cooperative interaction of the pluripotency factors Oct4 and Sox2 with the histone deacetylase HDAC1. Overexpressing SMAR1 sensitized CSCs to chemotherapy through SMAR1-dependent recruitment of HDAC2 to the promoter of the gene encoding the drug efflux pump ABCG2. Treating cultured CSCs or 4T1 tumor-bearing mice with the nonsteroidal anti-inflammatory drug aspirin restored expression and repression and enhanced tumor sensitivity to doxorubicin. Our findings reveal transcriptional mechanisms regulating that also regulate cancer stemness and chemoresistance and suggest that, by restoring expression, aspirin might enhance chemotherapeutic efficacy in patients with stem-like tumors.
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http://dx.doi.org/10.1126/scisignal.aay6077DOI Listing
October 2020

Anti-cancer potential of (1,2-dihydronaphtho[2,1-b]furan-2-yl)methanone derivatives.

Bioorg Med Chem Lett 2020 10 8;30(20):127476. Epub 2020 Aug 8.

Bose Institute, Division of Molecular Medicine, P-1/12, C.I.T. Scheme VII M, Kolkata 700054, India. Electronic address:

A series of 1,2-dihydronaphtho[2,1-b]furan derivatives were synthesized by cyclizing 1-(aryl/alkyl(arylthio)methyl)-naphthalen-2-ol and pyridinium bromides in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in very good yield. The synthesized compounds were evaluated for their anti-proliferative potential against human triple negative MDA-MB-468 and MCF-7 breast cancer cells and non-cancerous WI-38 cells (lung fibroblast cell) using MTT experiments. Among 21 synthesized compounds, three compounds (3a, 3b and 3 s) showed promising anti-cancer potential and compound 3b was found to have best anti-proliferative activities based on the results of several biochemical and microscopic experiments.
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http://dx.doi.org/10.1016/j.bmcl.2020.127476DOI Listing
October 2020

Renoprotective effect of Capsicum annum against ethanol-induced oxidative stress and renal apoptosis.

J Food Biochem 2021 03 23;45(3):e13325. Epub 2020 Jun 23.

Department of Physiology, Rammohan College, Kolkata, India.

The present study explored the ameliorative potency of aqueous extract of Capsicum annum (AqCA), against oxidative imbalance and renal toxicity induced by ethanol. Randomly grouped male Wistar rats (n = 6), were marked as ethanol-treated (2 g/kg bw, i.p.), CA (125 mg/kg bw, i.p.), CA (250 mg/kg bw, i.p.), ethanol pre-treated with CA (similar doses), and control (0.5 ml normal saline, i.p.), and treated for 30 consecutive days. Biochemical analysis of tissue and serum parameters was performed, along with histopathological and histochemical studies. Also, we performed TUNEL assay and western blotting for our experimental groups. Statistical analysis revealed significant (p ≤ .001) alteration in the levels of antioxidant enzymes, serum urea, creatinine, pro-inflammatory cytokines, and cleaved caspases, along with histopathological alterations in the ethanol-treated group. Prior treatment with AqCA prevented ethanol-induced alterations in tissue and serum parameters. These findings indicate that the extract of CA can protect renal cells from ethanol-induced damage by inhibiting oxidative stress, inflammatory response, and apoptosis. PRACTICAL APPLICATIONS: Chronic alcohol consumption is a major public health concern that leads to various diseases and social problems as well. It affects both the affluent and non-affluent society equally. Alcohol (ethanol) is a renowned hepato-toxicant and a well-documented risk factor for oxidative stress, with less known effect on the kidney. Thus, it is essential to investigate the effect of alcohol metabolism on the kidney to find a remedy to prevent it. The present investigation depicts the anti-oxidative and anti-inflammatory role of Capsicum annum against ethanol-induced renal damage. The outcome of this study can be utilized in the future for phytotherapeutic herbal drug formulation. Besides, the bioactive components identified in the study can be further explored by researchers or pharmaceutical corporates for potential therapeutic purpose against renal impairment.
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http://dx.doi.org/10.1111/jfbc.13325DOI Listing
March 2021

Corrigendum to "Folic acid conjugated curcumin loaded biopolymeric gum acacia microsphere for triple negative breast cancer therapy in invitro and invivo model" [Mater. Sci. Eng. C (2019) 204-216].

Mater Sci Eng C Mater Biol Appl 2020 Jun 25;111:110866. Epub 2020 Mar 25.

Department of Life Science and Biotechnology, Jadavpur University, Kolkata 700032, India. Electronic address:

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http://dx.doi.org/10.1016/j.msec.2020.110866DOI Listing
June 2020

Pyridoxine enhances chemo-responsiveness of breast cancer stem cells via redox reconditioning.

Free Radic Biol Med 2020 05 4;152:152-165. Epub 2020 Mar 4.

Division of Molecular Medicine, Bose Institute, P-1/12 CIT Scheme, VIIM, Kolkata, 700054, India. Electronic address:

A plethora of molecular strategies are employed by breast cancer stem cells (bCSCs) to evade chemotherapy-induced death signals, redox modulation being a crucial factor among those. Here, we observed that bCSCs are resistant to DNA damage and generate low ROS upon doxorubicin (Dox) treatment. Further exploration revealed inherently high NEIL2, a base excision repair (BER) enzyme that plays a key regulatory role in repairing DNA damage, in bCSCs. However, its role in modulating the redox status of bCSCs remains unexplored. In addition, Dox not only upregulates NEIL2 in bCSCs at both transcriptional and translational levels but also declines p300-induced acetylation thus activating NEIL2 and providing a protective effect against the stress inflicted by the genotoxic drug. However, when the redox status of bCSCs is altered by inducing high ROS, apoptosis of the resistant population is accomplished. Subsequently, when NEIL2 is suppressed in bCSCs, chemo-sensitization of the resistant population is enabled by redox reconditioning via impaired DNA repair. This signifies a possibility of therapeutically disrupting the redox balance in bCSCs to enhance their chemo-responsiveness. Our search for an inhibitor of NEIL2 revealed that vitamin B6, i.e., pyridoxine (PN), hinders NEIL2-mediated transcription-coupled repair process by not only decreasing NEIL2 expression but also inhibiting its association with RNA Pol II, thus stimulating DNA damage and triggering ROS. As a consequence of altered redox regulation, bCSCs become susceptible towards Dox, which then induces apoptosis via caspase cascade. These findings signify that PN enhances chemo-responsiveness of bCSCs via redox reconditioning.
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http://dx.doi.org/10.1016/j.freeradbiomed.2020.02.031DOI Listing
May 2020

Increased host ATP efflux and its conversion to extracellular adenosine is crucial for establishing infection.

J Cell Sci 2020 04 8;133(7). Epub 2020 Apr 8.

Department of Biochemistry, University of Calcutta, Kolkata 700019, West Bengal, India

Intracellular survival of demands rapid production of host ATP for its sustenance. However, a gradual decrease in intracellular ATP in spite of increased glycolysis suggests ATP efflux during infection. Accordingly, upon infection, we show here that ATP is exported and the major exporter was pannexin-1, leading to raised extracellular ATP levels. Extracellular ATP shows a gradual decrease after the initial increase, and analysis of cell surface ATP-degrading enzymes revealed induction of the ectonucleotidases CD39 and CD73. Ectonucleotidase-mediated ATP degradation leads to increased extracellular adenosine (eADO), and inhibition of CD39 and CD73 in infected cells decreased adenosine concentration and parasite survival, documenting the importance of adenosine in infection. Inhibiting adenosine uptake by cells did not affect parasite survival, suggesting that eADO exerts its effect through receptor-mediated signalling. We also show that induces the expression of adenosine receptors AR and AR, both of which are important for anti-inflammatory responses. Treating infected BALB/c mice with CD39 and CD73 inhibitors resulted in decreased parasite burden and increased host-favourable cytokine production. Collectively, these observations indicate that infection-induced ATP is exported, and after conversion into adenosine, propagates infection via receptor-mediated signalling.
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http://dx.doi.org/10.1242/jcs.239939DOI Listing
April 2020

Evaluation of wound healing activity of ethanol extract of L. leaf both and in diabetic mice model.

J Tradit Complement Med 2021 Jan 6;11(1):27-37. Epub 2019 Dec 6.

Department of Life Science and Biotechnology, Jadavpur University, 188, Raja S.C. Mullick Road, Kolkata, 700 032, West Bengal, India.

Background And Aim: The leaves of Linn (niú x ınguǒ; Bullock's heart), a member of Annonaceae family, have been used extensively in folk medicine; however, its wound healing potential is yet to be explored. Our aim was to investigate the wound healing ability of leaf extract and in streptozotocin induced diabetic mice model.

Material And Methods: We observed the plant extract induced proliferation and migration of primary human dermal fibroblast (HDF), human skin fibroblast cell line (GM00637) and human keratinocyte cell line (HACAT). The expression of transforming growth factor beta (TGF-β), connective tissue growth factor (CTGF), vascular endothelial growth factor (VEGF), alpha smooth muscle actin (α-SMA), matrix metalloproteinases (MMP-2, MMP-9), collagen-1, collagen-3, focal adhesion kinase (FAK) were evaluated by Western blot and gelatin zymography. Excisional diabetic wound model was used for wound healing assay. Furthermore, we processed wound tissue for histological and immunohistochemical study.

Result: L. leaf extract stimulates proliferation and migration of HDF, skin fibroblast and keratinocyte significantly in a dose dependent manner; expression of TGF-β, CTGF, VEGF, α-SMA, MMP-2, MMP-9, collagen-1, collagen-3, FAK increased. Additionally, an enhanced expression of phospho-SMAD2, phospho-SMAD3 in the treated cells indicated the activation of TGF-β signal transduction pathway, similarly increased expression of phospho-AkT suggested activation of PI3/AkT pathway. Expression of CTGF and α-SMA was also increased significantly in wound tissue. Mass spectrometric analysis revealed that mainly two compounds to be present in the extract: quercetin and β-sitosterol.

Conclusion: Collective data suggest that leaf extract may have a stimulatory effect in diabetic wound healing.
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http://dx.doi.org/10.1016/j.jtcme.2019.12.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817713PMC
January 2021

The oxidative dehydrogenation of a coumarinyl scaffold with copper ion and metal ion detection in human liver cancer cells (HepG2).

Dalton Trans 2019 Dec 27;48(48):17818-17830. Epub 2019 Nov 27.

Department of Chemistry, Jadavpur University, Kolkata-700032, India.

An unsymmetrical o-phenylenediamine derivative, L (7-hydroxy-4-methyl-8-(1-(phenyl- (pyridin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)-2H-chromen-2-one), has been synthesized from (E)-N-(phenyl(pyridine-2-yl)methylene)benzene-1,2-diamine with 7-hydroxy-4-methyl-2-oxo-2H-chromene-8-carbaldehyde and characterized by X-ray, IR, H NMR and ESI-MS spectral analyses. The X-ray structure shows L as a cyclic benzimidazole derivative, but it undergoes ring-opening upon reaction with transition metal ions. L is non-emissive in 9 : 1 (v/v) EtOH/HO (HEPES buffer, pH 7.4) but becomes highly fluorescent upon Zn coordination, and the emissive Zn(ii) complex undergoes transmetallation in the presence of Cu ions specifically, followed by amine to imine oxidation, i.e. an oxidative dehydrogenation (OD) reaction -(2e + 2H) occurs. The transmetallation of Zn from the complex by Cu (CuCl) separated the non-emissive X-ray diffractable crystal of [Cu(L'')Cl] (L'' = amine oxidized form of L). A square pyramidal [Cu(L'')][ClO] complex was also isolated from the reaction of L with Cu(CHCN)(ClO) in the presence of air, and in this complex the amine is also oxidized to the imine. Here, copper ions in the presence of air play an important role in the OD reaction of L as determined by EPR and cyclic voltammetry studies. The ligand, L, is used for Zn ion recovery from a municipally supplied water sample. A paper strip detection kit for Zn and Cu is designed using L. The ligand is also used for intracellular Zn detection in a human liver cancer cell line (HepG2).
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http://dx.doi.org/10.1039/c9dt03870aDOI Listing
December 2019

Activating transcription factor 3 modulates the macrophage immune response to Mycobacterium tuberculosis infection via reciprocal regulation of inflammatory genes and lipid body formation.

Cell Microbiol 2020 03 20;22(3):e13142. Epub 2019 Nov 20.

Department of Chemistry, Bose Institute, Kolkata, India.

Infection of macrophages by Mycobacterium tuberculosis elicits an immune response that clears the bacterium. However, the bacterium is able to subvert the innate immune response. Differential expression of transcription factors (TFs) is central to the dynamic balance of this interaction. Among other functions, TFs regulate the production of antibacterial agents such as nitric oxide, pro-inflammatory cytokines and neutral lipids which are stored in lipid bodies (LBs) and favour bacterial survival. Here, we demonstrate that the TF activating transcription factor 3 (ATF3) is upregulated early during infection of macrophages or mice. Depletion of ATF3 enhances mycobacterial survival in macrophages suggesting its host-protective role. ATF3 interacts with chromatin remodelling protein brahma-related gene 1 and both associate with the promoters of interleukin-12p40, interleukin-6 and nitric oxide synthase 2, to activate expression of these genes. Strikingly, ATF3 downregulates LB formation by associating at the promoters of positive regulators of LB formation such as cholesterol 25 hydroxylase and the microRNA-33 locus. ATF3 represses the association of the activating mark, acetyl histone H4 lysine 8 at the promoter of cholesterol 25 hydroxylase. Our study suggests opposing roles of ATF3 in regulation of distinct sets of macrophage genes during infection, converging on a host-protective immune response.
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http://dx.doi.org/10.1111/cmi.13142DOI Listing
March 2020

Three-Dimensional-Coordination Polymer of Zn(II)-Carboxylate: Structural Elucidation, Photoelectrical Conductivity, and Biological Activity.

ACS Omega 2019 Oct 17;4(18):17649-17661. Epub 2019 Oct 17.

Department of Chemistry, Department of Physics, and Department of Life Science and Biotechnology, Jadavpur University, Jadavpur, Kolkata 700032, India.

A newly designed mixed-ligand coordination polymer [Zn(bdc)(ppmh)(HO)] () (H = 1,4-benzene dicarboxylic acid, = -pyridin-2-yl-'-pyridin-4-ylmethylene-hydrazine) has been characterized using different physicochemical techniques. The structure has been confirmed by single crystal X-ray diffraction measurements. There are two pyridyl-N and one hydrazino-imine-N donor centers in , where two pyridyl-Ns bind simultaneously to two Zn(II) to serve as a bridging agent to form a coordination polymer. The 1,4-benzene dicarboxylato () is ligated via the aromatic dicarboxylato-O to form a one-dimensional (1D) chain. These two 1D chains about Zn(II) constitute a two-dimensional structure, which undergoes noncovalent interactions (C-H···π and π···π) to generate a three-dimensional supramolecular assembly. Electrical conductivity of is higher by 1 order (1.37 × 10 S/cm) than that of the free ligand, (6.2 × 10 S/cm). Especially, the responsivity of the compound was 56.21 mA/W, which is 11 times higher than that of the ligand (5.12 mA/W). The specific detectivity of the compound was 2.17 × 10 Jones, which is also almost 10 times higher with respect to the specific detectivity of the ligand-based device (4.53 × 10 Jones). The results show that the compound can be valuable for optoelectronic fields. The biological studies suggest that compound is antibacterial as well as a promising anticancer agent (LD, 42.2 μg/mL against HepG2 cells), while ligands remain silent. Investigation of the mechanism of the cell killing activity of compound accounts the generation of intracellular reactive oxygen species.
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http://dx.doi.org/10.1021/acsomega.9b01745DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6822105PMC
October 2019

The sensor kinase MtrB of regulates hypoxic survival and establishment of infection.

J Biol Chem 2019 12 25;294(52):19862-19876. Epub 2019 Oct 25.

Department of Chemistry, Bose Institute, Kolkata 700009, India

Paired two-component systems (TCSs), having a sensor kinase (SK) and a cognate response regulator (RR), enable the human pathogen to respond to the external environment and to persist within its host. Here, we inactivated the SK gene of the TCS MtrAB, , generating the strain Δ We show that loss reduces the bacterium's ability to survive in macrophages and increases its association with autophagosomes and autolysosomes. Notably, the Δ strain was markedly defective in establishing lung infection in mice, with no detectable lung pathology following aerosol challenge. Δ was less able to withstand hypoxic and acid stresses and to form biofilms and had decreased viability under hypoxia. Transcriptional profiling of Δ by gene microarray analysis, validated by quantitative RT-PCR, indicated down-regulation of the hypoxia-associated regulon, as well as genes associated with other pathways linked to adaptation of to the host environment. Using biochemical assays, we demonstrate that MtrB interacts with DosR (a noncognate RR) in a phosphorylation-independent manner. Electrophoretic mobility shift assays revealed that MtrB enhances the binding of DosR to the promoter, suggesting an unexpected role of MtrB in DosR-regulated gene expression in Taken together, these findings indicate that MtrB functions as a regulator of DosR-dependent gene expression and in the adaptation of to hypoxia and the host environment. We propose that MtrB may be exploited as a chemotherapeutic target against tuberculosis.
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http://dx.doi.org/10.1074/jbc.RA119.009449DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6937564PMC
December 2019

Aggregation-Induced Emission-Active Hydrazide-Based Probe: Selective Sensing of Al, HF , and Nitro Explosives.

ACS Omega 2019 May 14;4(5):8451-8464. Epub 2019 May 14.

Department of Chemistry and Department of Life Science and Biotechnology, Jadavpur University, Kolkata 700032, India.

()-'-((2-Hydroxynaphthalen-1-yl)methylene)picolinohydrazide (H-PNAP) shows aggregation-induced emission (AIE) strictly in a 90% water/MeOH (v/v) mixture at 540 nm, and the solid-state emission is blue-shifted to 509 nm upon excitation at 400 nm. The AIE activity of H-PNAP is selectively quenched by 2,4,6-trinitrophenol (TNP) and 2,4-dinitrophenol (DNP) out of different nitroaromatic compounds with a limit of detection (LOD) of 7.79 × 10 and 9.08 × 10 M, respectively. The probe is nonemissive in aqueous medium (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid, HEPES buffer, pH 7.2); however, it shows a strong emission to Al (λ, 490 nm) in the presence of 17 other biological metal ions, and the LOD is 2.09 nM which is far below the WHO recommended value (7.41 mM). The emission of the [Al(PNAP)(NO)] complex is quenched by HF (F and PO are weak quencher), and the LOD is as low as 15 nM. The probable mechanism of the sensing feature of the probe has been authenticated by H nuclear magnetic resonance titration, mass spectrometry, Fourier transform infrared spectroscopy, Benesi-Hildebrand plot, and Job's plot in each case. The probe has some practical applications such as recovery of Al from the drinking water sample, construction of the INHIBIT logic gate, and detection kits for Al and TNP/DNP by simple paper test strips. The probe, H-PNAP, has successfully been applied to the detection of intracellular Al and HF ions in the human breast cancer cell, MDA-MB-468.
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http://dx.doi.org/10.1021/acsomega.9b00369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6648475PMC
May 2019

Anti-cancer potential of novel glycosylated 1,4-substituted triazolylchalcone derivatives.

Bioorg Med Chem Lett 2019 10 19;29(19):126615. Epub 2019 Aug 19.

Bose Institute, Division of Molecular Medicine, P-1/12, C.I.T. Scheme VII M, Kolkata 700054, India. Electronic address:

A series of glycosylated 1,4-substituted triazolyl chalcone derivatives (8a-f and 14a-r) were synthesized in high yield using 1,3-cycloaddition (Click chemistry) of d-glucosyl azides with a variety of propargylated chalcone derivatives followed by de-O-acetylation. The synthesized compounds were evaluated for their cytotoxic potential against the human breast carcinoma cell lines and non-cancerous cells. The MTT assay identified three promising cytotoxic compounds (14c, 14i and 14l) and further biochemical and microscopic studies were carried out with the best compound 14i among the active compounds.
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http://dx.doi.org/10.1016/j.bmcl.2019.08.019DOI Listing
October 2019

Protective Effect of Resveratrol on Benzo(a)Pyrene Induced Dysfunctions of Steroidogenesis and Steroidogenic Acute Regulatory Gene Expression in Leydig Cells.

Front Endocrinol (Lausanne) 2019 30;10:272. Epub 2019 Apr 30.

Division of Molecular Medicine, Bose Institute, Calcutta Improvement Trust Scheme VIIM, Kolkata, India.

Benzo(a)pyrene [B(a)P] is the toxic environmental Polycyclic Aromatic Hydrocarbon (PAH), that exerts male reproductive dysfunctions. In this study the molecular mechanism of B(a)P induced Leydig cell steroidogenic dysfunctions and its protective mechanism of action with a natural Aryl hydrocarbon receptor (AhR) antagonist and anti-oxidant, Resveratrol (Res) has been investigated. B(a)P exposure induced ROS mediated steroidogenic imbalance via activation of p38MAPK and repression of testosterone level as well as other steroidogenic enzymes like CYPIIA1, 3β-HSD, 17β-HSD expressions. B(a)P exposure decreased StAR protein expression along with increased DAX-1, a transcriptional repressor of gene. Along with that B(a)P decreased the expression of SF-1 that acts as a transcriptional inducer of StAR gene expression. The study has established Resveratrol as a potential agent combating the deleterious effect of B(a)P on Leydig cell steroidogenesis. Resveratrol treatment resulted significant protection against B(a)P by scavenging ROS and modulating the transcriptional regulation of anti-oxidant enzymes. Furthermore, Resveratrol also prevented stress kinase like p38 MAPK activation and increased StAR protein expression through the reduction of DAX-1 expression. Moreover, the testosterone production was efficiently restored with Resveratrol treatment. ChIP assay also revealed that resveratrol improved SF-1expression which further increased the gene expression. Resveratrol acted efficiently against B(a)P, through its anti-oxidative properties as well as inhibits p38MAPK and increased steroidogenesis and StAR expression through the modulation of gene expression.
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http://dx.doi.org/10.3389/fendo.2019.00272DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6502972PMC
April 2019

Aryl quinolinyl hydrazone derivatives as anti-inflammatory agents that inhibit TLR4 activation in the macrophages.

Eur J Pharm Sci 2019 Jun 16;134:102-115. Epub 2019 Apr 16.

Bose Institute, Division of Molecular Medicine, P-1/12, C.I.T. Scheme VII M, Kolkata 700054, India. Electronic address:

A series of aryl 7-chloroquinolinyl hydrazone derivatives (3a-u) have been synthesized in 55-76% yield using simple reaction condition. The synthesized compounds were evaluated for their anti-inflammatory activities based on their ability to inhibit pro-inflammatory cytokine secretion from the macrophages after stimulation with lipopolysaccharide (LPS). Three compounds appeared as promising anti-inflammatory agents. The mechanism of inflammatory activity of the potent compound 3e was further investigated using a series of biochemical, molecular and microscopic techniques. Further structure activity relationship (SAR) study was carried out to validate the anti-inflammatory activities of the active compounds. Our experimental data revealed that the active moiety i.e. compound 3e majorly causes inhibition of TLR4 signaling pathway and this appears to be the novel functional attribute of this compound.
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http://dx.doi.org/10.1016/j.ejps.2019.04.016DOI Listing
June 2019

An Study for Targeted Delivery of Curcumin in Human Triple Negative Breast Carcinoma Cells Using Biocompatible PLGA Microspheres Conjugated with Folic Acid.

J Nanosci Nanotechnol 2019 07;19(7):3720-3733

Department of Life Science and Biotechnology, Jadavpur University, Kolkata 700032, India.

Among the different types of polymeric vehicles, (PLGA) is biodegradable and has emerged as promising tool for the delivery of cancer therapeutics. The salient features of PLGA micro carriers include prolonged circulation time, increased tumor localization and biodegradability and effectiveness of the therapeutics. We have synthesized PLGA microspheres where curcumin can be loaded and thereby increases its bioavailability. The cytotoxicity of curcumin ([email protected]) microspheres was evaluated on triple negative breast cancer (TNBC) cell lines. They were found to induce apoptosis by perturbing the mitochondrial membrane potential. [email protected]@FA induces apoptosis in human triple negative breast cancer cells by up-regulating Cleaved caspase-3 and down regutes p-AKT. The study in BALB/C mice model exhibited more tumor regression in case of [email protected]@FA microspheres. Our results suggests that these microspheres can be an effective vehicle for delivery of hydrophobic drugs to the folate over expressed cancer cells.
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http://dx.doi.org/10.1166/jnn.2019.16292DOI Listing
July 2019

Natural product inspired allicin analogs as novel anti-cancer agents.

Bioorg Chem 2019 05 29;86:259-272. Epub 2019 Jan 29.

Bose Institute, Division of Molecular Medicine, P-1/12, C.I.T. Scheme VII M, Kolkata 700054, India. Electronic address:

A series of novel analogs of Allicin (S-allyl prop-2-ene-1-sulfinothioate) present in garlic has been synthesized in high yield. Synthesized 23 compounds were evaluated against different breast cancer cells (MDA-MB-468 and MCF-7) and non-cancer cells (WI38). Four compounds (3f, 3h, 3m and 3u) showed significant cytotoxicity against cancer cells whereas nontoxic to the normal cells. Based on the LD values and selectivity index (SI), compound 3h (S-p-methoxybenzyl (p-methoxyphenyl)methanesulfinothioate) was considered as most promising anticancer agent amongst the above three compounds. Further bio-chemical studies confirmed that compound 3h promotes ROS generation, changes in mitochondrial permeability transition and induced caspase mediated DNA damage and apoptosis.
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http://dx.doi.org/10.1016/j.bioorg.2019.01.057DOI Listing
May 2019

Exploits Macrophage Heme Oxygenase-1 To Neutralize Oxidative Burst and TLR Signaling-Dependent Host Defense.

J Immunol 2019 02 28;202(3):827-840. Epub 2018 Dec 28.

Department of Biochemistry, University of Calcutta, Kolkata 700019, India;

Suppression of host oxidative burst is essential for survival of the intracellular parasite Screening of macrophage antioxidant enzymes during infection revealed marked upregulation of the heme-degrading enzyme, heme oxygenase-1 (HO-1). Moreover, HO-1-silenced RAW macrophages depicted increased superoxide production and decreased parasite survival. HO-1 induction decreased cellular heme content, thereby inhibiting the heme-dependent maturation of gp91phox, a catalytic component of major reactive oxygen species-producing enzyme NAD(P)H oxidase. Decreased gp91phox expression resulted in reduced stability of p22phox, another component of the catalytic center of NAD(P)H oxidase. Replenishing infected cells with exogenous heme reversed these effects and restored NAD(P)H oxidase activity. Persistent HO-1 expression at late hour of infection prompted us to investigate its effect on other host defense parameters, and inhibition study revealed a reciprocal relationship of HO-1 with host proinflammatory responses. Among all the HO-1-mediated heme degradation products (CO, Fe, and biliverdin), only CO documented potent anti-inflammatory effects. Quenching of CO during infection increased the production of disease-resolving cytokines IL-12 and TNF-α. Coimmunoprecipitation experiments revealed that CO inhibited the interaction of TLR4 with MyD88 and TIR domain-containing adapter-inducing IFN-β, thereby dampening the activation of NF-κB and IFN regulatory factor 3-mediated production of proinflammatory cytokines. Administration of HO-1 inhibitor tin protoporphyrin IX dichloride in infected BALB/c mice led to a decrease in liver and spleen parasite burden along with increased production of IL-12 and TNF-α. These results suggest that HO-1 on one hand inhibits reactive oxygen species generation and on the other hand downregulates host favorable cytokine responses, thereby facilitating intramacrophage parasite survival.
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http://dx.doi.org/10.4049/jimmunol.1800958DOI Listing
February 2019

Folic acid conjugated curcumin loaded biopolymeric gum acacia microsphere for triple negative breast cancer therapy in invitro and invivo model.

Mater Sci Eng C Mater Biol Appl 2019 Feb 22;95:204-216. Epub 2018 Oct 22.

Department of Life Science and Biotechnology, Jadavpur University, Kolkata 700032, India. Electronic address:

Among the different types of biomaterials, natural excipients gum acacia (GA) is economic and has the potential for controlled drug delivery. We have synthesized GA microspheres by co-precipitation method and characterized them by XRD, FESEM, H NMR, FTIR, UV visible spectra and DLS. Despite its potential anti-cancer activity, solubility of curcumin is very low rendering its limit in application. We have used GA microspheres where curcumin can be loaded comfortably and thereby increases its bioavailability. The cytotoxicity of curcumin encapsulated GA microspheres was evaluated on triple negative breast cancer cell lines. They were found to induce apoptosis by perturbing the mitochondrial membrane potential. Folic acid was conjugated to curcumin encapsulated GA microspheres, for delivering it specifically to the cancer cells. The in-vivo study in BALB/C mice model exhibited more tumor regression in case of folic acid targeted curcumin encapsulated GA microsphere. Our results implicates that these microspheres can be an effective therapeutic agent to folate receptors over expressing cancer cells.
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http://dx.doi.org/10.1016/j.msec.2018.10.071DOI Listing
February 2019

Multiple paralogues of α-SNAP in Giardia lamblia exhibit independent subcellular localization and redistribution during encystation and stress.

Parasit Vectors 2018 Oct 4;11(1):539. Epub 2018 Oct 4.

Department of Biochemistry, Bose Institute, P 1/12 CIT Road Scheme VII M, Kolkata, West Bengal, 700054, India.

Background: The differently-diverged parasitic protist Giardia lamblia is known to have minimal machinery for vesicular transport. Yet, it has three paralogues of SNAP, a crucial component that together with NSF brings about disassembly of the cis-SNARE complex formed following vesicle fusion to target membranes. Given that most opisthokont hosts of this gut parasite express only one α-SNAP, this study was undertaken to determine whether these giardial SNAP proteins have undergone functional divergence.

Results: All three SNAP paralogues are expressed in trophozoites, encysting trophozoites and cysts. Even though one of them clusters with γ-SNAP sequences in a phylogenetic tree, functional complementation analysis in yeast indicates that all the three proteins are functionally orthologous to α-SNAP. Localization studies showed a mostly non-overlapping distribution of these α-SNAPs in trophozoites, encysting cells and cysts. In addition, two of the paralogues exhibit substantial subcellular redistribution during encystation, which was also seen following exposure to oxidative stress. However, the expression of the three genes remained unchanged during this redistribution process. There is also a difference in the affinity of each of these α-SNAP paralogues for GlNSF.

Conclusions: None of the genes encoding the three α-SNAPs are pseudogenes and the encoded proteins are likely to discharge non-redundant functions in the different morphological states of G. lamblia. Based on the difference in the interaction of individual α-SNAPs with GlNSF and their non-overlapping pattern of subcellular redistribution during encystation and under stress conditions, it may be concluded that the three giardial α-SNAP paralogues have undergone functional divergence. Presence of one of the giardial α-SNAPs at the PDRs of flagella, where neither GlNSF nor any of the SNAREs localize, indicates that this α-SNAP discharges a SNARE-independent role in this gut pathogen.
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http://dx.doi.org/10.1186/s13071-018-3112-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6172762PMC
October 2018
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