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An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely... more
An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely... more
An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
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Correction for ‘Endoplasmic reticulum targeting tumour selective photocytotoxic oxovanadium(iv) complexes having vitamin-B6 and acridinyl moieties’ by Samya Banerjee et al., Dalton Trans., 2016, 45, 783–796.
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An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely... more
An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
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Monoclonal antibodies have been used as probes to study the architecture of several plant viruses over the past decade. These studies complement the information obtained through X-ray crystallography and help in delineating epitopes on... more
Monoclonal antibodies have been used as probes to study the architecture of several plant viruses over the past decade. These studies complement the information obtained through X-ray crystallography and help in delineating epitopes on the surface of the virus. The monoclonal antibodies that recognize distinct epitopes also aid in unravelling the mechanisms of assembly/disassembly of virus particles. Group-specific and strain-specific monoclonal antibodies are widely used in the classification of viruses. The significant developments made in this emerging area are reviewed here with specific examples.
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Vitamin-B6 (VB6) Schiff base (H2L) copper(II) complexes of pyridyl bases, viz. Cu(bpy)(L)] (1), Cu(phen)(L)] (2) and Cu(dppz)(L)] (3), where bpy is 2,2'-bipyridine, phen is 1,10-phenanthroline and dppz is... more
Vitamin-B6 (VB6) Schiff base (H2L) copper(II) complexes of pyridyl bases, viz. Cu(bpy)(L)] (1), Cu(phen)(L)] (2) and Cu(dppz)(L)] (3), where bpy is 2,2'-bipyridine, phen is 1,10-phenanthroline and dppz is dipyrido3,2-a:2',3'c]phenazine are synthesized, characterized and their phto-induced anticancer activity studied. The non-electrolytic one electron paramagnetic complexes exhibit a d-d band near 700 nm in DMF. The dppz complex intercalatively binds to calf-thymus DNA with binding constant (K-b) values of similar to 10(6) M-1. This complex exhibits low chemical nuclease activity but excellent DNA photocleavage activity when irradiated with red light of 705 nm forming (OH)-O-center dot radical. It displays remarkable photocytotoxicity in human cervical cancer cells (HeLa) giving IC50 value of 0.9 mu M in visible light (400-700 nm) while being less toxic in darkness (IC50 : 23 mu M). The cellular uptake of the complexes seems to be via VB6 transporting membrane carrier med...
Research Interests: Chemistry and Schiff Base
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Boron-dipyrromethene (BODIPY) based photosensitizers as porphyrinoids and curcumin as natural product possess exciting photophysical features suitable for theranostic applications, namely, imaging and photodynamic therapy (PDT). Limited... more
Boron-dipyrromethene (BODIPY) based photosensitizers as porphyrinoids and curcumin as natural product possess exciting photophysical features suitable for theranostic applications, namely, imaging and photodynamic therapy (PDT). Limited aqueous solubility and insufficient physiological stability, however, reduce their efficacy significantly. We have designed a novel strategy to deliver these two unusable cytotoxins simultaneously in cancer cells and herein, report the synthesis, characterization and imaging-assisted photocytotoxicity of three zinc(II) complexes containing N3-donor dipicolylamine (dpa) ligands (L1-3) and O,O-donor curcumin (Hcur) viz. [Zn(L1)(cur)]Cl (1), [Zn(L2)(cur)]Cl (2) and [Zn(L3)(cur)]Cl (3), where L2 and L3 have pendant fluorescent BODIPY and non-emissive di-iodo-BODIPY moieties. Metal chelation imparted remarkable biological stability (pH ∼7.4) to the respective ligands and induces significant aqueous solubility. These ternary complexes could act as replacements of the existing metalloporphyrin-based PDT photosensitizers as their visible-light photosensitizing ability is reinforced by the dual presence of blue light absorbing curcumin and green light harvesting BODIPY units. Complex 2 having emissive BODIPY unit L2 and curcumin, showed mitochondria selective localization in HeLa, MCF-7 cancer cells and complex 3, the di-iodinated analogue of complex 2, exhibited type-I/II PDT activity via inducing apoptosis through mitochondrial membrane disruption in cancer cells while being significantly nontoxic in dark and to the healthy cells.
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Natural killer (NK) cells comprise of ∼70% of the immune cell population in the maternal decidua and ∼15% of the mononuclear cells in the peripheral blood. The decidual NK cells capable of producing high levels of cytokines are... more
Natural killer (NK) cells comprise of ∼70% of the immune cell population in the maternal decidua and ∼15% of the mononuclear cells in the peripheral blood. The decidual NK cells capable of producing high levels of cytokines are functionally distinct from the peripheral NK cells that exhibit high cytotoxicity. The numbers of peripheral NK cells and their cytotoxicity potential have been correlated with pregnancy outcome. In the same context, glycodelin, an immunomodulatory protein, has been recognized to be essential for the establishment and maintenance of pregnancy, and its' reduced levels are associated with recurrent spontaneous abortions. We investigated the effect of glycodelin on the peripheral NK cells. Our results reveal that glycodelin suppresses the cytotoxicity of peripheral NK cells via downregulating perforin, granzyme B and IFNγ. Glycodelin also induces caspase-dependent death in only activated peripheral NK cells, the effect suggested to be mediated by glycodelin upon engaging with the CD7 cell surface receptor. Thus, during pregnancy, glycodelin modulates the function and the number of cytotoxic NK cells that pose a deleterious effect on the fetus, a semi-allograft. This study provides insights into the mechanism of the regulatory effect of glycodelin on NK cells and could possibly be exploited for the management of miscarriages.
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Correction for ‘Impact of metal binding on the antitumor activity and cellular imaging of a metal chelator cationic imidazopyridine derivative’ by Mithun Roy et al., Dalton Trans., 2011, 40, 4855–4864.
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Human liver tissue is preferable over nonhuman liver tissue for preclinical drug screening, as the former can better predict side effects specific to humans. However, due to limited supply and ethical issues with human liver tissue, it is... more
Human liver tissue is preferable over nonhuman liver tissue for preclinical drug screening, as the former can better predict side effects specific to humans. However, due to limited supply and ethical issues with human liver tissue, it is desirable to develop an animal model having functional human liver tissue. In this study, we have established an ectopic functional human liver tissue in a mouse model, using a minimally-invasive method. Firstly, a human liver tissue mass using HepG2 cells and poly(N-isopropylacrylamide) (PNIPAAm) incorporated poly(ethylene glycol)-alginate-gelatin (PAG) cryogel matrix was developed in vitro. It was later implanted in mouse peritoneal cavity using a 16 G needle. Viscoelastic nature along with low Young's modulus provided injectable properties to the cryogel. We confirmed minimal cell loss/death while injecting. Further, by in vivo study efficacy of both injectable and surgical implantation approaches were compared. No significant difference in terms of cell infiltration, human serum albumin (HSA) secretion and enzyme activity confirmed efficacy. This model developed using a minimally-invasive approach can overcome the limitations of surgical implantation due to its cost effective and user friendly nature.
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Tumor necrosis factor-α (TNFα), one of the major pro-inflammatory cytokines, plays a key role in an effective immune response. However, the chronic presence of TNFα can lead to several inflammatory disorders like... more
Tumor necrosis factor-α (TNFα), one of the major pro-inflammatory cytokines, plays a key role in an effective immune response. However, the chronic presence of TNFα can lead to several inflammatory disorders like rheumatoid arthritis, psoriasis, Crohn’s disease etc. Inhibition of TNFα by pharmacological inhibitors or antibodies has proven to be effective in palliative treatment to some extent. The aim of this study was to develop an anti-TNFα antibody which may be used as a therapeutic option to inhibit TNFα-mediated cytotoxicity. We characterized several hybridoma clones secreting monoclonal antibodies (mAbs) to human-TNFα. Four mAbs rescued L929 fibroblast cells from TNFα-triggered cell death and one of these, namely C8 was found to have the highest affinity. To gain insights into the mechanism by which mAb C8 inhibits human TNFα-mediated toxicity, the epitope corresponding to the mAb was delineated. The antigenic determi...
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Though a number of new drugs have been and are being formulated to treat cancer, newer therapeutic approaches are needed due to increased instances of drug resistance and toxic side effects. One relatively new approach for treatment is... more
Though a number of new drugs have been and are being formulated to treat cancer, newer therapeutic approaches are needed due to increased instances of drug resistance and toxic side effects. One relatively new approach for treatment is immunotherapy, using antibodies or ligands to cell surface molecules as vehicles to deliver toxins to specific cells, thus increasing the efficacy of the treatment by several folds. Such conjugates, of antibodies and toxins termed ‘immunotoxins’ are generated either as chemical conjugates using hetero-bifunctional cross-linkers that link the antibody to the toxin, or as ‘fusion proteins’, wherein, the gene for the antibody and the gene for the toxin are cloned together as one construct into bacterial expression systems and expressed as recombinant proteins. Several toxins, mainly the inhibitors of translation, are being explored for preparing immunotoxins. This chapter provides an overview of the treatment modalities adopted to date for the cancer management and introduces the field of immunotherapy. The chapter also focuses on the different toxins used in generating immunotoxins and on those that have made it to clinical trials.
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Monoclonal antibodies raised against human serum retinol-binding protein (hRBP) were used as probes for the study of the antigenic determinants of hRBP and those shared with the same protein from other species. The antibodies could be... more
Monoclonal antibodies raised against human serum retinol-binding protein (hRBP) were used as probes for the study of the antigenic determinants of hRBP and those shared with the same protein from other species. The antibodies could be classified into four distinct groups and react with the homologous proteins from the rat as well as the rabbit sera. Three of these antibodies recognize sequential or continuous epitopes while the remaining antibody is directed against a discontinuous or conformational epitope. By chemical cleavage with cyanogen bromide, the domains recognized by the monoclonal antibodies could be delineated. By solid-phase synthetic approach, the core sequences recognized by two of these monoclonal antibodies were identified to amino acid sequences 45-51 and 128-131 of the primary amino acid sequence of hRBP.
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Oxovanadium(iv) complexes of vitamin-B6 Schiff base, viz., [VO(HL(1)/L(2)/L(3))(B)]Cl (), where B is 2,2'-bipyridine (bpy in and ), 11-(9-acridinyl)dipyrido[3,2-a:2',3'-c]phenazine (acdppz in and ), H2L(1)·HCl is... more
Oxovanadium(iv) complexes of vitamin-B6 Schiff base, viz., [VO(HL(1)/L(2)/L(3))(B)]Cl (), where B is 2,2'-bipyridine (bpy in and ), 11-(9-acridinyl)dipyrido[3,2-a:2',3'-c]phenazine (acdppz in and ), H2L(1)·HCl is 3-hydroxy-5-(hydroxymethyl)-4-(((2-hydroxyphenyl)imino)methyl)-2-methylpyridin-1-ium chloride (in and ), HL(2) is 2-(((2-(1H-imidazol-4-yl)ethyl)imino)methyl)phenol (in ) and HL(3) is 4-(((2-(1H-imidazol-4-yl)ethyl)imino)methyl)-5-(hydroxymethyl)-2-methylpyridin-3-ol (in ) were synthesized, characterized and their cellular uptake, photo-activated cytotoxicity and intracellular localization were studied. Complexes , as the perchlorate salt of , and , as the hexafluorophosphate salt of , were structurally characterized. Vitamin-B6 transporting membrane carrier (VTC) mediated entry into tumour cells in preference to the normal ones seems to be responsible for the higher cellular uptake of the complexes into HeLa and MCF-7 cells over MCF-10A cells. Complexes and hav...
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Copper(ii) acetylacetonates of N,N,N-donor dipicolylamine (dpa) ligands, viz. [Cu(L1)(acac)]ClO4 (1), [Cu(L2)(acac)]ClO4 (2) and [Cu(L3)(acac)]ClO4 (3), where L1 is benzyldipicolylamine (bzdpa), L2 and L3 are non-iodinated and diiodinated... more
Copper(ii) acetylacetonates of N,N,N-donor dipicolylamine (dpa) ligands, viz. [Cu(L1)(acac)]ClO4 (1), [Cu(L2)(acac)]ClO4 (2) and [Cu(L3)(acac)]ClO4 (3), where L1 is benzyldipicolylamine (bzdpa), L2 and L3 are non-iodinated and diiodinated BODIPY (borondipyrromethene) ligands and Hacac is acetylacetone, were synthesized and characterized and their photocytotoxicity was studied. The BODIPY complex 2, structurally characterized by X-ray crystallography, has copper(ii) in a distorted square-pyramidal geometry (degree of trigonality, τ5 = 0.28). The one-electron paramagnetic and redox active copper(ii) complexes displayed 1 : 1 electrolytic behaviour in polar organic solvents. The BODIPY complexes 2 and 3 showed respective visible bands at 498 and 539 nm in 5% DMSO-phosphate buffered saline (PBS). Complex 2 displayed an emission band at 511 nm in 5% DMSO-PBS (λex = 465 nm) with a fluorescence quantum yield (ΦF) value of 0.15. Cellular imaging using this complex showed significant mitocho...
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Hepatitis C virus (HCV) is a leading cause of chronic viral hepatitis, but an effective vaccine is still not available to prevent infection. Use of neutralizing antibodies could be a potential therapeutic option. In this study, presence... more
Hepatitis C virus (HCV) is a leading cause of chronic viral hepatitis, but an effective vaccine is still not available to prevent infection. Use of neutralizing antibodies could be a potential therapeutic option. In this study, presence of anti-HCV antibodies in HCV-infected patients' was assessed from 50 patients and examined for the presence of neutralizing antibodies using the 'hepatitis C virus like particles'. Antibodies from two samples exhibited significant inhibitory activity suggesting that these may neutralize viral infection. Antigenic determinants generating the neutralizing antibodies from these two samples were delineated by epitope mapping using the core, E1 and E2 regions and a stretch of 45 amino acid peptide (E2C45) derived from the C-terminal region of HCV-E2 protein (aa 634-679) was designed. Results suggest that this hitherto uncharacterized region has the potential to generate neutralizing antibodies against HCV and thus effective in preventing viru...
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Glycodelin, also known as placental protein 14, has been implicated in endometriosis-related infertility. To determine the role of glycodelin and its glycosylated state, the influence of recombinant nonglycosylated-glycodelin... more
Glycodelin, also known as placental protein 14, has been implicated in endometriosis-related infertility. To determine the role of glycodelin and its glycosylated state, the influence of recombinant nonglycosylated-glycodelin (nongly-glycodelin) and glycosylated-glycodelin (gly-glycodelin) on human sperm function was evaluated. Whereas there was a significant (P<0.001) increase in the capacitation of nongly-glycodelin-treated spermatozoa compared with untreated controls (28.8 +/- 1.0% v. 21 +/- 1.5% respectively), treatment of spermatozoa with gly-glycodelin markedly (P<0.001) inhibited capacitation (10.7 +/- 0.3%); acrosome reaction (AR) remained unaltered in all treatments. In a zona-free hamster egg penetration assay, the egg penetration index was higher (P<0.001) with nongly-glycodelin-treated spermatozoa (3.4 +/- 0.3) than with gly-glycodelin-treated spermatozoa (0.4 +/- 0.1) and untreated spermatozoa (1.6 +/- 0.2). A similar influence of glycodelin on capacitation was...
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Research Interests: Endocrinology, Genetics, Cognitive Science, Clinical Microbiology, Biological Sciences, and 15 moreBrain, Humans, Female, Animals, Glycoproteins, Francisella tularensis, Clinical Sciences, Forestry Sciences, Fluorescent Antibody Technique, Avian Diseases, Epitopes, Enzyme Linked Immunosorbent Assay, Case Control Studies, Antigenic Variation, and Cardiovascular medicine and haematology
A specific protein exhibiting immunological cross-reactivity with chicken riboflavin carrier protein has been purified to homogeneity from human amniotic fluid by use of ion-exchange and affinity chromatography. The protein is similar to... more
A specific protein exhibiting immunological cross-reactivity with chicken riboflavin carrier protein has been purified to homogeneity from human amniotic fluid by use of ion-exchange and affinity chromatography. The protein is similar to its avian counterpart in terms of molecular size, distribution of 125I-labelled tryptic peptides during finger printing, and preferential binding to riboflavin. Immunologically, they are homologous since most of the monoclonal antibodies raised against the avian protein cross-react with the purified human vitamin carrier.
Research Interests: Biochemistry, Biological Sciences, Pregnancy, Humans, Female, and 12 moreAnimals, Monoclonal Antibodies, Amniotic Fluid, Biochemical, Sodium Dodecyl Sulfate-Polyacrylamide Gel Electrophoresis, Membrane transport proteins, CHEMICAL SCIENCES, Rats, Chickens, Molecular weight, Riboflavin, and Medical and Health Sciences
BODIPY-appended copper(ii) complexes of curcumin show a remarkable PDT effect in visible light in HeLa cells via apoptosis with mitochondrial localization.
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ABSTRACT
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ABSTRACT
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Research Interests: Immunohistochemistry, Biological Sciences, Cell line, Molecular and cellular biology, Humans, and 15 moreMice, Female, Animals, Monoclonal Antibodies, Pituitary Gland, Gonadotropin Releasing Hormone, Western blot, Breast carcinoma, Ovarian Carcinoma, Monoclonal Antibody, Amino Acid Sequence, Recombinant Proteins, Molecular Sequence Data, Breast Neoplasms, and Medical and Health Sciences
Monoclonal antibodies were raised to the idiotype of a gonadotropin releasing hormone (GnRH) specific antibody, one of which was found to bind specifically to GnRH receptors present on pituitary gonadotrophs, placental... more
Monoclonal antibodies were raised to the idiotype of a gonadotropin releasing hormone (GnRH) specific antibody, one of which was found to bind specifically to GnRH receptors present on pituitary gonadotrophs, placental syncytiotrophoblasts and testicular Leydig cells. These observations were confirmed by Western and ligand blotting as well as by the ability of the antibody to induce an increase in intracellular Ca++ in a mouse gonadotroph cell-line viz., alpha T3-1.
Research Interests: Calcium, Western blotting, Cell line, Humans, Mice, and 14 moreSheep, Female, Animals, Male, Monoclonal Antibodies, Aged, Pituitary Gland, Rats, Gonadotropin Releasing Hormone, Biochemistry and molecular biology, Leydig cells, Cell Surface Markers, Enzyme Linked Immunosorbent Assay, and Biochemistry and cell biology
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Antipeptide and antiidiotypic antibodies to several receptors are known to mimic their respective ligands in transducing signals on binding their receptors. In our attempts to study gonadotropin releasing hormone receptor, antipeptide and... more
Antipeptide and antiidiotypic antibodies to several receptors are known to mimic their respective ligands in transducing signals on binding their receptors. In our attempts to study gonadotropin releasing hormone receptor, antipeptide and antiidiotypic monoclonal antibodies specific to the receptor were established earlier. The antipeptide mAb F1G4 was to a synthetic peptide corresponding to the extracellular domain of human GnRH receptor and the antiidiotypic mAb 4D10C1 was to the idiotype of a GnRH specific mAb. Here we report the physiological effects of the two mAbs on binding the receptor, as investigated using in vitro cultures of (a) human term placental villi and (b) rat pituitaries. The mAb 4D10C1 exerted a dose-dependent release of human chorionic gonadotropin in cultures of human term placental villi as well as luteinising and follicle stimulating hormones in cultures of rat pituitaries.
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An oxovanadium(iv) Schiff base vitamin-B6 complex of (acridinyl)dipyridophenazine shows ER-targeted photo-induced anticancer activity while being non-toxic in the dark and to normal cells.