Tapan Mukherjee | Maharishi Markandeshwar University (original) (raw)
Papers by Tapan Mukherjee
The consumption of diet-based naturally bioactive metabolites is preferred to synthetic material ... more The consumption of diet-based naturally bioactive metabolites is preferred to synthetic material in order to avert health-associated disorders. Among the plant-derived polyphenols, kaempferol (KMF) is considered as a valuable functional food ingredient with a broad range of therapeutic applications such as anti-cancer, antioxidant and anti-inflammatory uses. KMF acts on a range of intracellular as well as extracellular targets involved in the cell signaling pathways that in turn are known to regulate the hallmarks of cancer growth progressions like apoptosis, cell cycle, invasion or metastasis, angiogenesis and inflammation. Importantly, the understanding of mechanisms of action of KMF-mediated therapeutic effects may help the scientific community to design novel strategies for the treatment of dreadful diseases. The current review summarizes the various types of molecular targets of KMF in cancer cells as well as other health-associated disorders. In addition, this review also highlights the absorption, metabolism and epidemiological findings.
Melanoma is a cancer associated with melanocytes of epidermis. There has been a consistent increa... more Melanoma is a cancer associated with melanocytes of epidermis. There has been a consistent increase in the number of melanoma patients because of the depletion of the ozone layer which makes it of paramount importance to explore the immunogenic potential of various peptides in melanoma therapy. In the current study, a mutated decapeptide (ELAGIGILTV) epitope ID 12941 was taken from the melanoma antigen recognized by T-cells. This epitope displayed relatively better affinity for histocompatibility leukocyte antigen influencing the proliferation of cytotoxic T-cells. Immunogenicity of the oligopeptide can be further intensified by its simultaneous binding to the programmed death receptor of the T lymphocytes. We have used the molecular dynamics (MD) simulation approach to reveal the dynamics of the decapeptide and its consequences to immunogenic effects. The dynamics have ensembled various conformations of the peptide which have been clustered in their representative conformers. During the dynamics, the peptide was found to fold to its conformation with a minimum free energy. Moreover, multiple analysis of the MD trajectory has provided many physiochemical features involved in the biological activity to improve the immunogenicity of this antigenic peptide. The manuscript concludes by proposing this decapeptide as a potential vaccine for the melanoma cancer.
The consumption of diet-based naturally bioactive metabolites is preferred to synthetic material ... more The consumption of diet-based naturally bioactive metabolites is preferred to synthetic material in order to avert health-associated disorders. Among the plant-derived polyphenols, kaempferol (KMF) is considered as a valuable functional food ingredient with a broad range of therapeutic applications such as anti-cancer, antioxidant and anti-inflamma-tory uses. KMF acts on a range of intracellular as well as extracellular targets involved in the cell signaling pathways that in turn are known to regulate the hallmarks of cancer growth progressions like apoptosis, cell cycle, invasion or metastasis, angiogenesis and inflammation. Importantly, the understanding of mechanisms of action of KMF-mediated therapeutic effects may help the scientific community to design novel strategies for the treatment of dreadful diseases. The current review summarizes the various types of molecular targets of KMF in cancer cells as well as other health-associated disorders. In addition, this review also highlights the absorption, metabolism and epidemiological findings.
Despite significant improvements in the technical aspects of cancer diagnosis and management, it ... more Despite significant improvements in the technical aspects of cancer diagnosis and management, it is still a leading cause of mortality worldwide. Although, the development of a variety of therapeutic strategies with effective mechanisms of action is increasing, the advanced understanding of molecular mechanisms of cancer initiation and progression is still the important consequence. Reactive oxygen species (ROS) with great concern due to the ability to modulate cell survival and cell death signaling pathways are could be considered to design the effective anti-cancer strategies. Several anti-cancer agents used for the treatment of various cancers regulates ROSs generation which subsequently modulate the pro-apoptotic molecules, expression of various transcription factors including Sp1, AP1, NF-kβ, and other pro-oncogenic genes that are engaged in cancer cell proliferation, survival and metastasis. Concentration dependent ROS has distinct role in different cancer processes like in apoptosis, cancer survival, autophagy, angiogenesis, metastasis, and inflammation. Radiation and potent agents used in chemotherapy are working on the phenomenon of ROS generation that inhibit cancer process. With the intense understanding of ROS's role in the particular cancer process which is inevitable in cancer, may be used in health care to improve patient's survival rate. The current review presents all the proposed molecular interactions of ROS with their known cellular targets in cancer cell.
Plants are known to be an assortment of bioactive metabolites that are being utilized to cure dif... more Plants are known to be an assortment of bioactive metabolites that are being utilized to cure different life undermining and ceaseless sicknesses. The evaluation of therapeutic activity of such bioactive phytochemicals may leads to new paths for the researchers to create or enhance novel restorative ways to deal with disorders, for example, cancer growth, cardiovascular and neurodegenerative disorders. Cordycepin, isothiocyanate, melatonin, oleanolic acid, ursolic acid, kaempferol, quercetin and gambogic acids are some among the classifications of such plant-based remedial metabolites with broad spectrum of various biological activities. These metabolites are known to interact negatively with a variety of cellular signalling pathways and events that are found to be associated with cancer progression including programmed cell death (apoptosis), movement of cancer cells through blood to various organs of the body (invasion), attachment and grow as a new cancer (metastasis), formation of new blood vessels (angiogenesis) and inflammation. Studies recommend that these moieties could be utilized to build up the effective therapies towards the treatment and prevention of life threatening diseases. This mini review highlights the recent trends and future prospective about these wonderful moieties.
Despite extensive efforts done in the recent decades, cancer has still remained an incurable diso... more Despite extensive efforts done in the recent decades, cancer has still remained an incurable disorder. On the other hand, there is no doubt that different natural compounds possess a huge potential to suppress the promotion and progression of tumorigenesis, and numerous studies have described the possible molecular mechanisms of such substances. Probably one of the most efficient ways to hinder the multiplication of cancer cells is to arrest their cell cycle progression. Therefore, in the current article, a detailed review is presented about the arrest of cell cycle in different phases followed by exposure of cancer cells to two natural dietary agents, quercetin, and ursolic acid. Both these compounds have previously been shown to exert anticancer properties, whereas pleiotropic action mechanisms were proposed. The current work describes a variety of molecules occupied in regulation of cell cycle progression and transition between different phases initiated by treatment of cancer cells with the respective flavonoid and triterpenoid. It is clear that better knowledge about the processes and molecules involved in cell cycle, as well as possibilities to modulate such mechanisms by natural compounds, may lead to the development of more efficient and targeted chemopreventive and chemotherapeutic strategies in the future.
The Biochemical journal, Jan 15, 1996
The 49 kDa penicillin-binding protein (PBP) of Mycobacterium smegmatis catalyses the hydrolysis o... more The 49 kDa penicillin-binding protein (PBP) of Mycobacterium smegmatis catalyses the hydrolysis of the peptide or S-ester bond of carbonyl donors R1-CONH-CHR2-COX-CHR2-COO- (where X is NH or S). In the presence of a suitable amino acceptor, the reaction partitions between the transpeptidation and hydrolysis pathways, with the amino acceptor, behaving as a simple alternative nucleophile at the level of the acyl-enzyme. By virtue of its N-terminal sequence similarity, the 49 kDa PBP represents one of the class of monofunctional low-molecular-mass PBPs. An immunologically related protein of M(r) 52,000 is present in M. tuberculosis. The 49 kDa PBP is sensitive towards amoxycillin, imipenem, flomoxef and cefoxitin.
Turkish Journal of Biology, 2014
Inflammation can be broadly understood as a successive immune response of an organism's immune sy... more Inflammation can be broadly understood as a successive immune response of an organism's immune system towards nonnative or foreign antigens. This is a protective mechanism of the immune system, mediated by diverse immunological cells, to ensure homeostasis of an individual. Once activated, these immunological cells release a number of cytokines, chemokines, reactive oxygen species, reactive nitrogen species, histamines, prostaglandins, and other materials leading to inflammation. Tumor cells express altered proteins due to mutations of their genes, DNA modifications such as histone modification, DNA methylation, or other mechanisms of altered protein expression. The body's immunological cells actively recognize these altered proteins, now acting as tumor antigens, and eliminate the tumor cell; this is popularly known as tumor immunosurveillance. However, in unmanaged or inexorable circumstances, tumor cells escape from immunosurveillance mechanisms. This ultimately leads to the cascading events of cancer development and progression. T regulatory cells, tumor-associated macrophages, and myeloid-derived suppressor cells are pronounced cells involved in immunosuppression. These cells not only dodge the immune system's surveillance but also significantly increase the survival, proliferation, and metastasis rates of tumor cells. They hinder T cytotoxic activation by secreting inhibitory cytokines (which inhibit the antitumor activity of natural killer cells) along with dendritic cells and disrupt presentation of antigens, ultimately leading to cancer development. On their own, these cells have emerged as promising therapeutic targets in cancer immunotherapy. This review highlights some of the mechanisms by which these cells escape immunosurveillance and mediate immune suppression.
Despite extensive efforts done in the recent decades, cancer has still remained an incurable diso... more Despite extensive efforts done in the recent decades, cancer has still remained an incurable disorder. On the other hand, there is no doubt that different natural compounds possess a huge potential to suppress the promotion and progression of tumorigenesis, and numerous studies have described the possible molecular mechanisms of such substances. Probably one of the most efficient ways to hinder the multiplication of cancer cells is to arrest their cell cycle progression. Therefore, in the current article, a detailed review is presented about the arrest of cell cycle in different phases followed by exposure of cancer cells to two natural dietary agents, quercetin, and ursolic acid. Both these compounds have previously been shown to exert anticancer properties, whereas pleiotropic action mechanisms were proposed. The current work describes a variety of molecules occupied in regulation of cell cycle progression and transition between different phases initiated by treatment of cancer cells with the respective flavonoid and triterpenoid. It is clear that better knowledge about the processes and molecules involved in cell cycle, as well as possibilities to modulate such mechanisms by natural compounds, may lead to the development of more efficient and targeted chemopreventive and chemotherapeutic strategies in the future.
We report that arsenic trioxide (ATO) and 17-beta-estradiol (E2) abolish each other's independent... more We report that arsenic trioxide (ATO) and 17-beta-estradiol (E2) abolish each other's independent cell signaling effects in respect of cell survival and proliferation/migration of breast cancer (MCF-7) cells. The possibility that this is due to binding of ATO to E2 was confirmed through difference absorption spec-troscopy, chromatography-coupled voltammometry and 1-D 1 H and 13 C NMR spectroscopy. Binding leads to attenuation of E2's hydroxyl 1 H peaks at its C17 and C3 carbon positions. The results suggest that ATO and E2 can titrate each other's levels, potentially explaining why sustained arsenic exposure tends to be associated with delays in age of menarche, advanced age of menopause, poorer sperm quality, higher overall morbidity in men, and lower incidences of breast cancer in women in some arsenic-contaminated areas.
Plants are known to be an assortment of bioactive metabolites that are being utilized to cure dif... more Plants are known to be an assortment of bioactive metabolites that are being utilized to cure different life undermining and ceaseless sicknesses. The evaluation of therapeutic activity of such bioactive phytochemicals may leads to new paths for the researchers to create or enhance novel restorative ways to deal with disorders, for example, cancer growth, cardiovascular and neurodegenerative disorders. Cordycepin, isothiocyanate, melatonin, oleanolic acid, ursolic acid, kaempferol, quercetin and gambogic acids are some among the classifications of such plant-based remedial metabolites with broad spectrum of various biological activities. These metabolites are known to interact negatively with a variety of cellular signalling pathways and events that are found to be associated with cancer progression including programmed cell death (apoptosis), movement of cancer cells through blood to various organs of the body (invasion), attachment and grow as a new cancer (metastasis), formation of new blood vessels (angiogenesis) and inflammation. Studies recommend that these moieties could be utilized to build up the effective therapies towards the treatment and prevention of life threatening diseases. This mini review highlights the recent trends and future prospective about these wonderful moieties.
Phytochemical screening, isolation, antimicrobial and antioxidant activities of methanol, ethanol... more Phytochemical screening, isolation, antimicrobial and antioxidant activities of methanol, ethanol chloroform and water crude extracts of Myristica fragrans and Tinospora cordifolia were studied in this work. The aim of this work is to ascertain the level of antimicrobial activity and antioxidant properties of different solvent extracts of M. fragrans and T. cordifolia as well as isolated phytochemicals. The preliminary screening of various extracts was carried out using E. coli, C. sakazakii and P. aeruginosa by agar well diffusion method. The DPPH method used to determine the antioxidant potential of plant extracts and isolated phytochemicals. Myristicin and eugenol present in methanolic extracts exhibit direct relation with antimicrobial and antioxidant activity while palmatine and berberine could be responsible for T. cordifolia activities. The result showed that M. fragrans and T. cordifolia extracts have pharmocological active compounds with great antioxidant and antimicrobial effects. The results obtained from this study justify the use of this plant in traditional folk medicine and provide leads which could be further exploited for development of new and potent antimicrobials. Copy Right, IJAR, 2016,. All rights reserved.
The wide applications of Bisphenol A (BPA) in food and packaging industry have increased the expo... more The wide applications of Bisphenol A (BPA) in food and packaging industry have increased the exposure and risk of this chemical towards the human population with its endocrine disrupting effects. BPA is used among the various products with everyday use. The vulnerable population especially infants are at an increased risk of exposure as BPA is widely used in baby feeding bottles. The present study was carried out to determine the amount of BPA migrating in to the water samples from the polycarbonate material of baby feeding bottles, drinking water bottles, microwave safe plastic and canned food products. Different brands of polycarbonate feeding bottles, water bottles and microwave safe plastic were included in the study and BPA was determined in the water samples using HPLC with fluorescence detector. BPA leach out was also determined in the canned products which included canned fruits and canned vegetables.The testrevealed 2.80 mg/L of BPA leaching for the feeding water bottles,0.06 mg/L from the drinking water bottles, 0.008 mg/L from microwave safe plastic bowls and 0.067 mg/L in the canned products. Copy Right, IJAR, 2016,. All rights reserved.
Background: Curcumin (Ccm) has shown immense potential as an antimalarial agent; however its low ... more Background: Curcumin (Ccm) has shown immense potential as an antimalarial agent; however its low solubility and less bioavailability attenuate the in vivo efficacy of this potent compound. In order to increase Ccm's bioavailability, a number of organic/inorganic polymer based nanoparticles have been investigated. However, most of the present day nano based delivery systems pose a conundrum with respect to their complex synthesis procedures, poor in vivo stability and toxicity issues. Peptides due to their high biocompatibility could act as excellent materials for the synthesis of nanoparticulate drug delivery systems. Here, we have investigated dehydrophenylalanine (ΔPhe) di-peptide based self-assembled nanoparticles for the efficient delivery of Ccm as an antimalarial agent. The self-assembly and curcumin loading capacity of different ΔPhe dipeptides, phenylalanine–α,β-dehydrophenylalanine (FΔF), arginine-α,β-dehydrophenylalanine (RΔF), valine-α,β-dehydrophenylalanine (VΔF) and methonine-α,β-dehydrophenylalanine (MΔF) were investigated for achieving enhanced and effective delivery of the compound for potential anti-malarial therapy. Results: FΔF, RΔF, VΔF and MΔF peptides formed different types of nanoparticles like nanotubes and nanovesicles under similar assembling conditions. Out of these, F∆F nanotubes showed maximum curcumin loading capacity of almost 68 % W/W. Ccm loaded F∆F nanotubes (Ccm-F∆F) showed comparatively higher (IC 50 , 3.0 µM) inhibition of Plasmodium falciparum (Indo strain) as compared to free Ccm (IC 50 , 13 µM). Ccm-F∆F nano formulation further demonstrated higher inhibition of parasite growth in malaria infected mice as compared to free Ccm. The dipeptide nano-particles were highly biocompatible and didn't show any toxic effect on mammalian cell lines and normal blood cells. Conclusion: This work provides a proof of principle of using highly biocompatible short peptide based nanoparticles for entrapment and in vivo delivery of Ccm leading to an enhancement in its efficacy as an antimalarial agent.
Beta lactamase is one of the main reasons behind the development of antibiotic resistance among p... more Beta lactamase is one of the main reasons behind the development of antibiotic resistance among pathogenic bacteria against beta lactam antibiotics. S. typhi, Gram negative bacteria is main causative agent among human population in developing countries has developed resistance against β-lactam antibiotics which are already in their fourth generation. The availability of a good quality three dimensional structure of target protein is necessary for the development of therapeutic drugs. A good quality three dimensional structure of Beta lactamase TEM-1 from S. typhi was not available. In this study, primary, secondary and tertiary structures of Beta lactamase TEM-1 from S. typhi were predicted using Expasy’s Protpram, PSIPRED and Homology modelling method respectively. The modelled structure was energy minimized and molecular dynamics and simulation studies were performed to investigate how the predicted model behaves structurally, dynamically
and thermodynamically using Gromacs 5.1 molecular dynamics and simulation tool. The structure was predicted to be fast attaining the normal temperature (300 K), pressure (1 Bar) and density (1000 Kg/m3) values during NVT (constant volume and normal temperature) and NPT (constant normal pressure and normal temperature) simulation steps within the given timeframe using OPLSAA
force field and SPC/E water model. The predicted structure was also validated using PROCHECK. The predicted model was found to be stereo-chemically stable in Ramachandran plot produced by PROCHECK as more than 93% residues were falling under core regions of the plot.
The structure will aid in discovery of more efficient alternative therapeutic drugs against typhoid
causing S. typhi.
TURKISH JOURNAL OF BIOLOGY, 2014
Inflammation can be broadly understood as a successive immune response of an organism's immune sy... more Inflammation can be broadly understood as a successive immune response of an organism's immune system towards nonnative or foreign antigens. This is a protective mechanism of the immune system, mediated by diverse immunological cells, to ensure homeostasis of an individual. Once activated, these immunological cells release a number of cytokines, chemokines, reactive oxygen species, reactive nitrogen species, histamines, prostaglandins, and other materials leading to inflammation. Tumor cells express altered proteins due to mutations of their genes, DNA modifications such as histone modification, DNA methylation, or other mechanisms of altered protein expression. The body's immunological cells actively recognize these altered proteins, now acting as tumor antigens, and eliminate the tumor cell; this is popularly known as tumor immunosurveillance. However, in unmanaged or inexorable circumstances, tumor cells escape from immunosurveillance mechanisms. This ultimately leads to the cascading events of cancer development and progression. T regulatory cells, tumor-associated macrophages, and myeloid-derived suppressor cells are pronounced cells involved in immunosuppression. These cells not only dodge the immune system's surveillance but also significantly increase the survival, proliferation, and metastasis rates of tumor cells. They hinder T cytotoxic activation by secreting inhibitory cytokines (which inhibit the antitumor activity of natural killer cells) along with dendritic cells and disrupt presentation of antigens, ultimately leading to cancer development. On their own, these cells have emerged as promising therapeutic targets in cancer immunotherapy. This review highlights some of the mechanisms by which these cells escape immunosurveillance and mediate immune suppression.
Chitinases occur in a wide range of organisms including bacteria, fungi, plants, insects, and ani... more Chitinases occur in a wide range of organisms including bacteria, fungi, plants, insects, and animals. Chitinase has been widely used as one of the mycobiocontrol agent as it degrades chitin which is a chain homopolymer of N- acetylglucosamine (GlcNAc) connected by β-1,4 glucosidic linkages. Beauveria bassiana is an insect pathogenic fungus successfully used as an insect pest control agent worldwide. In this paper, 21 different chitinase, endochitinase and chit proteins / gene retrieved from Swiss-Prot database are analysed and characterized. Various Bioinformatics and molecular modeling approach were adopted to explore properties and structure of chitinase gene in Entomopathogenic fungi. Primary structure analysis predicted the physico-chemical properties such as pI, EC, AI, GRAVY and instability index and provides data about these proteins and their properties. Subcellular localization were predicted by MultiLoc software. Prediction of motifs, patterns, disulfide bridges and secondary structure were performed for functional characterization. Three dimensional structures for chitinase like proteins are not available as yet at PDB. Therefore, homology models for were developed. The modelling of the three dimensional structure of these proteins shows that models generated by Modeller were more acceptable in comparison to that by Geno3D and Swiss Model.
The need for new and useful compounds to provide help and respite in all aspects of the human lif... more The need for new and useful compounds to provide help and respite in all aspects of the human life is always growing. It has
been well familiar that some plant pathogenic fungi can be developed as inundative biological control agents to kill or inhibit the activity of
some insects which cause a large destruction in the crop fields and in forest vegetation. Today, scientist worked on a number of fungi for
making it as a myco-insecticide because some fungi contain chitinase genes which degrade the outer hard cuticle of the insect pest.
Beauvaria bassiana is one of the fungi which is widely used in insect-pest control in forest as well as in crop fields. In the present study, DNA
of Beauvaria bassiana were extracted and amplified by PCR using designed primer from GeneRunner software for isolation of Bbchit1 gene.
Bbchit1 gene showed significant similarities with Cordyceps sp., Metarhizium , Trichoderma with endochitinase, chitinase and chit gene. The
sequencing of the gene was done and subjected to ClustalX for alignment to detect conserved region and a phylogenetic tree was also
generated. These results may be useful in characterizing the evolutionary mechanism of the species. The pathogenecity of the fungi was also
detected against insect larvae of Helicoverpa armigera on the basis of time and temperature. This study will facilitate the identification of virulence genes and the development of improved bio-control strains with customized properties.
Journal of Microbial & Biochemical Technology
Of late, nanotechnology has emerged to be a very reliable bridge in trying to club salient fields... more Of late, nanotechnology has emerged to be a very reliable bridge in trying to club salient fields of natural sciences on a common platform. Deservedly enough, nanomaterials have enabled numerous unconventional wonders to be accomplished through their incorporation, either on a singular or on complexed form. However, the rapid strides being accomplished on a tremendously high speed have sheerly ignored some ground realities in terms of ethical considerations. Bestowed with unconventional physicochemical properties and material behavior, nanomaterials are often surprise candidates in terms of their interaction with several other materials. This leads to a significant difficulty in the discard of integrated structures or individual materials carrying nanomaterials. The emerging threat of nanotoxicology from interactions thereof has attracted significant attention of environmental conservationists from the different corners of the world. In terms of physicochemical behavior, it is extre...
The consumption of diet-based naturally bioactive metabolites is preferred to synthetic material ... more The consumption of diet-based naturally bioactive metabolites is preferred to synthetic material in order to avert health-associated disorders. Among the plant-derived polyphenols, kaempferol (KMF) is considered as a valuable functional food ingredient with a broad range of therapeutic applications such as anti-cancer, antioxidant and anti-inflammatory uses. KMF acts on a range of intracellular as well as extracellular targets involved in the cell signaling pathways that in turn are known to regulate the hallmarks of cancer growth progressions like apoptosis, cell cycle, invasion or metastasis, angiogenesis and inflammation. Importantly, the understanding of mechanisms of action of KMF-mediated therapeutic effects may help the scientific community to design novel strategies for the treatment of dreadful diseases. The current review summarizes the various types of molecular targets of KMF in cancer cells as well as other health-associated disorders. In addition, this review also highlights the absorption, metabolism and epidemiological findings.
Melanoma is a cancer associated with melanocytes of epidermis. There has been a consistent increa... more Melanoma is a cancer associated with melanocytes of epidermis. There has been a consistent increase in the number of melanoma patients because of the depletion of the ozone layer which makes it of paramount importance to explore the immunogenic potential of various peptides in melanoma therapy. In the current study, a mutated decapeptide (ELAGIGILTV) epitope ID 12941 was taken from the melanoma antigen recognized by T-cells. This epitope displayed relatively better affinity for histocompatibility leukocyte antigen influencing the proliferation of cytotoxic T-cells. Immunogenicity of the oligopeptide can be further intensified by its simultaneous binding to the programmed death receptor of the T lymphocytes. We have used the molecular dynamics (MD) simulation approach to reveal the dynamics of the decapeptide and its consequences to immunogenic effects. The dynamics have ensembled various conformations of the peptide which have been clustered in their representative conformers. During the dynamics, the peptide was found to fold to its conformation with a minimum free energy. Moreover, multiple analysis of the MD trajectory has provided many physiochemical features involved in the biological activity to improve the immunogenicity of this antigenic peptide. The manuscript concludes by proposing this decapeptide as a potential vaccine for the melanoma cancer.
The consumption of diet-based naturally bioactive metabolites is preferred to synthetic material ... more The consumption of diet-based naturally bioactive metabolites is preferred to synthetic material in order to avert health-associated disorders. Among the plant-derived polyphenols, kaempferol (KMF) is considered as a valuable functional food ingredient with a broad range of therapeutic applications such as anti-cancer, antioxidant and anti-inflamma-tory uses. KMF acts on a range of intracellular as well as extracellular targets involved in the cell signaling pathways that in turn are known to regulate the hallmarks of cancer growth progressions like apoptosis, cell cycle, invasion or metastasis, angiogenesis and inflammation. Importantly, the understanding of mechanisms of action of KMF-mediated therapeutic effects may help the scientific community to design novel strategies for the treatment of dreadful diseases. The current review summarizes the various types of molecular targets of KMF in cancer cells as well as other health-associated disorders. In addition, this review also highlights the absorption, metabolism and epidemiological findings.
Despite significant improvements in the technical aspects of cancer diagnosis and management, it ... more Despite significant improvements in the technical aspects of cancer diagnosis and management, it is still a leading cause of mortality worldwide. Although, the development of a variety of therapeutic strategies with effective mechanisms of action is increasing, the advanced understanding of molecular mechanisms of cancer initiation and progression is still the important consequence. Reactive oxygen species (ROS) with great concern due to the ability to modulate cell survival and cell death signaling pathways are could be considered to design the effective anti-cancer strategies. Several anti-cancer agents used for the treatment of various cancers regulates ROSs generation which subsequently modulate the pro-apoptotic molecules, expression of various transcription factors including Sp1, AP1, NF-kβ, and other pro-oncogenic genes that are engaged in cancer cell proliferation, survival and metastasis. Concentration dependent ROS has distinct role in different cancer processes like in apoptosis, cancer survival, autophagy, angiogenesis, metastasis, and inflammation. Radiation and potent agents used in chemotherapy are working on the phenomenon of ROS generation that inhibit cancer process. With the intense understanding of ROS's role in the particular cancer process which is inevitable in cancer, may be used in health care to improve patient's survival rate. The current review presents all the proposed molecular interactions of ROS with their known cellular targets in cancer cell.
Plants are known to be an assortment of bioactive metabolites that are being utilized to cure dif... more Plants are known to be an assortment of bioactive metabolites that are being utilized to cure different life undermining and ceaseless sicknesses. The evaluation of therapeutic activity of such bioactive phytochemicals may leads to new paths for the researchers to create or enhance novel restorative ways to deal with disorders, for example, cancer growth, cardiovascular and neurodegenerative disorders. Cordycepin, isothiocyanate, melatonin, oleanolic acid, ursolic acid, kaempferol, quercetin and gambogic acids are some among the classifications of such plant-based remedial metabolites with broad spectrum of various biological activities. These metabolites are known to interact negatively with a variety of cellular signalling pathways and events that are found to be associated with cancer progression including programmed cell death (apoptosis), movement of cancer cells through blood to various organs of the body (invasion), attachment and grow as a new cancer (metastasis), formation of new blood vessels (angiogenesis) and inflammation. Studies recommend that these moieties could be utilized to build up the effective therapies towards the treatment and prevention of life threatening diseases. This mini review highlights the recent trends and future prospective about these wonderful moieties.
Despite extensive efforts done in the recent decades, cancer has still remained an incurable diso... more Despite extensive efforts done in the recent decades, cancer has still remained an incurable disorder. On the other hand, there is no doubt that different natural compounds possess a huge potential to suppress the promotion and progression of tumorigenesis, and numerous studies have described the possible molecular mechanisms of such substances. Probably one of the most efficient ways to hinder the multiplication of cancer cells is to arrest their cell cycle progression. Therefore, in the current article, a detailed review is presented about the arrest of cell cycle in different phases followed by exposure of cancer cells to two natural dietary agents, quercetin, and ursolic acid. Both these compounds have previously been shown to exert anticancer properties, whereas pleiotropic action mechanisms were proposed. The current work describes a variety of molecules occupied in regulation of cell cycle progression and transition between different phases initiated by treatment of cancer cells with the respective flavonoid and triterpenoid. It is clear that better knowledge about the processes and molecules involved in cell cycle, as well as possibilities to modulate such mechanisms by natural compounds, may lead to the development of more efficient and targeted chemopreventive and chemotherapeutic strategies in the future.
The Biochemical journal, Jan 15, 1996
The 49 kDa penicillin-binding protein (PBP) of Mycobacterium smegmatis catalyses the hydrolysis o... more The 49 kDa penicillin-binding protein (PBP) of Mycobacterium smegmatis catalyses the hydrolysis of the peptide or S-ester bond of carbonyl donors R1-CONH-CHR2-COX-CHR2-COO- (where X is NH or S). In the presence of a suitable amino acceptor, the reaction partitions between the transpeptidation and hydrolysis pathways, with the amino acceptor, behaving as a simple alternative nucleophile at the level of the acyl-enzyme. By virtue of its N-terminal sequence similarity, the 49 kDa PBP represents one of the class of monofunctional low-molecular-mass PBPs. An immunologically related protein of M(r) 52,000 is present in M. tuberculosis. The 49 kDa PBP is sensitive towards amoxycillin, imipenem, flomoxef and cefoxitin.
Turkish Journal of Biology, 2014
Inflammation can be broadly understood as a successive immune response of an organism's immune sy... more Inflammation can be broadly understood as a successive immune response of an organism's immune system towards nonnative or foreign antigens. This is a protective mechanism of the immune system, mediated by diverse immunological cells, to ensure homeostasis of an individual. Once activated, these immunological cells release a number of cytokines, chemokines, reactive oxygen species, reactive nitrogen species, histamines, prostaglandins, and other materials leading to inflammation. Tumor cells express altered proteins due to mutations of their genes, DNA modifications such as histone modification, DNA methylation, or other mechanisms of altered protein expression. The body's immunological cells actively recognize these altered proteins, now acting as tumor antigens, and eliminate the tumor cell; this is popularly known as tumor immunosurveillance. However, in unmanaged or inexorable circumstances, tumor cells escape from immunosurveillance mechanisms. This ultimately leads to the cascading events of cancer development and progression. T regulatory cells, tumor-associated macrophages, and myeloid-derived suppressor cells are pronounced cells involved in immunosuppression. These cells not only dodge the immune system's surveillance but also significantly increase the survival, proliferation, and metastasis rates of tumor cells. They hinder T cytotoxic activation by secreting inhibitory cytokines (which inhibit the antitumor activity of natural killer cells) along with dendritic cells and disrupt presentation of antigens, ultimately leading to cancer development. On their own, these cells have emerged as promising therapeutic targets in cancer immunotherapy. This review highlights some of the mechanisms by which these cells escape immunosurveillance and mediate immune suppression.
Despite extensive efforts done in the recent decades, cancer has still remained an incurable diso... more Despite extensive efforts done in the recent decades, cancer has still remained an incurable disorder. On the other hand, there is no doubt that different natural compounds possess a huge potential to suppress the promotion and progression of tumorigenesis, and numerous studies have described the possible molecular mechanisms of such substances. Probably one of the most efficient ways to hinder the multiplication of cancer cells is to arrest their cell cycle progression. Therefore, in the current article, a detailed review is presented about the arrest of cell cycle in different phases followed by exposure of cancer cells to two natural dietary agents, quercetin, and ursolic acid. Both these compounds have previously been shown to exert anticancer properties, whereas pleiotropic action mechanisms were proposed. The current work describes a variety of molecules occupied in regulation of cell cycle progression and transition between different phases initiated by treatment of cancer cells with the respective flavonoid and triterpenoid. It is clear that better knowledge about the processes and molecules involved in cell cycle, as well as possibilities to modulate such mechanisms by natural compounds, may lead to the development of more efficient and targeted chemopreventive and chemotherapeutic strategies in the future.
We report that arsenic trioxide (ATO) and 17-beta-estradiol (E2) abolish each other's independent... more We report that arsenic trioxide (ATO) and 17-beta-estradiol (E2) abolish each other's independent cell signaling effects in respect of cell survival and proliferation/migration of breast cancer (MCF-7) cells. The possibility that this is due to binding of ATO to E2 was confirmed through difference absorption spec-troscopy, chromatography-coupled voltammometry and 1-D 1 H and 13 C NMR spectroscopy. Binding leads to attenuation of E2's hydroxyl 1 H peaks at its C17 and C3 carbon positions. The results suggest that ATO and E2 can titrate each other's levels, potentially explaining why sustained arsenic exposure tends to be associated with delays in age of menarche, advanced age of menopause, poorer sperm quality, higher overall morbidity in men, and lower incidences of breast cancer in women in some arsenic-contaminated areas.
Plants are known to be an assortment of bioactive metabolites that are being utilized to cure dif... more Plants are known to be an assortment of bioactive metabolites that are being utilized to cure different life undermining and ceaseless sicknesses. The evaluation of therapeutic activity of such bioactive phytochemicals may leads to new paths for the researchers to create or enhance novel restorative ways to deal with disorders, for example, cancer growth, cardiovascular and neurodegenerative disorders. Cordycepin, isothiocyanate, melatonin, oleanolic acid, ursolic acid, kaempferol, quercetin and gambogic acids are some among the classifications of such plant-based remedial metabolites with broad spectrum of various biological activities. These metabolites are known to interact negatively with a variety of cellular signalling pathways and events that are found to be associated with cancer progression including programmed cell death (apoptosis), movement of cancer cells through blood to various organs of the body (invasion), attachment and grow as a new cancer (metastasis), formation of new blood vessels (angiogenesis) and inflammation. Studies recommend that these moieties could be utilized to build up the effective therapies towards the treatment and prevention of life threatening diseases. This mini review highlights the recent trends and future prospective about these wonderful moieties.
Phytochemical screening, isolation, antimicrobial and antioxidant activities of methanol, ethanol... more Phytochemical screening, isolation, antimicrobial and antioxidant activities of methanol, ethanol chloroform and water crude extracts of Myristica fragrans and Tinospora cordifolia were studied in this work. The aim of this work is to ascertain the level of antimicrobial activity and antioxidant properties of different solvent extracts of M. fragrans and T. cordifolia as well as isolated phytochemicals. The preliminary screening of various extracts was carried out using E. coli, C. sakazakii and P. aeruginosa by agar well diffusion method. The DPPH method used to determine the antioxidant potential of plant extracts and isolated phytochemicals. Myristicin and eugenol present in methanolic extracts exhibit direct relation with antimicrobial and antioxidant activity while palmatine and berberine could be responsible for T. cordifolia activities. The result showed that M. fragrans and T. cordifolia extracts have pharmocological active compounds with great antioxidant and antimicrobial effects. The results obtained from this study justify the use of this plant in traditional folk medicine and provide leads which could be further exploited for development of new and potent antimicrobials. Copy Right, IJAR, 2016,. All rights reserved.
The wide applications of Bisphenol A (BPA) in food and packaging industry have increased the expo... more The wide applications of Bisphenol A (BPA) in food and packaging industry have increased the exposure and risk of this chemical towards the human population with its endocrine disrupting effects. BPA is used among the various products with everyday use. The vulnerable population especially infants are at an increased risk of exposure as BPA is widely used in baby feeding bottles. The present study was carried out to determine the amount of BPA migrating in to the water samples from the polycarbonate material of baby feeding bottles, drinking water bottles, microwave safe plastic and canned food products. Different brands of polycarbonate feeding bottles, water bottles and microwave safe plastic were included in the study and BPA was determined in the water samples using HPLC with fluorescence detector. BPA leach out was also determined in the canned products which included canned fruits and canned vegetables.The testrevealed 2.80 mg/L of BPA leaching for the feeding water bottles,0.06 mg/L from the drinking water bottles, 0.008 mg/L from microwave safe plastic bowls and 0.067 mg/L in the canned products. Copy Right, IJAR, 2016,. All rights reserved.
Background: Curcumin (Ccm) has shown immense potential as an antimalarial agent; however its low ... more Background: Curcumin (Ccm) has shown immense potential as an antimalarial agent; however its low solubility and less bioavailability attenuate the in vivo efficacy of this potent compound. In order to increase Ccm's bioavailability, a number of organic/inorganic polymer based nanoparticles have been investigated. However, most of the present day nano based delivery systems pose a conundrum with respect to their complex synthesis procedures, poor in vivo stability and toxicity issues. Peptides due to their high biocompatibility could act as excellent materials for the synthesis of nanoparticulate drug delivery systems. Here, we have investigated dehydrophenylalanine (ΔPhe) di-peptide based self-assembled nanoparticles for the efficient delivery of Ccm as an antimalarial agent. The self-assembly and curcumin loading capacity of different ΔPhe dipeptides, phenylalanine–α,β-dehydrophenylalanine (FΔF), arginine-α,β-dehydrophenylalanine (RΔF), valine-α,β-dehydrophenylalanine (VΔF) and methonine-α,β-dehydrophenylalanine (MΔF) were investigated for achieving enhanced and effective delivery of the compound for potential anti-malarial therapy. Results: FΔF, RΔF, VΔF and MΔF peptides formed different types of nanoparticles like nanotubes and nanovesicles under similar assembling conditions. Out of these, F∆F nanotubes showed maximum curcumin loading capacity of almost 68 % W/W. Ccm loaded F∆F nanotubes (Ccm-F∆F) showed comparatively higher (IC 50 , 3.0 µM) inhibition of Plasmodium falciparum (Indo strain) as compared to free Ccm (IC 50 , 13 µM). Ccm-F∆F nano formulation further demonstrated higher inhibition of parasite growth in malaria infected mice as compared to free Ccm. The dipeptide nano-particles were highly biocompatible and didn't show any toxic effect on mammalian cell lines and normal blood cells. Conclusion: This work provides a proof of principle of using highly biocompatible short peptide based nanoparticles for entrapment and in vivo delivery of Ccm leading to an enhancement in its efficacy as an antimalarial agent.
Beta lactamase is one of the main reasons behind the development of antibiotic resistance among p... more Beta lactamase is one of the main reasons behind the development of antibiotic resistance among pathogenic bacteria against beta lactam antibiotics. S. typhi, Gram negative bacteria is main causative agent among human population in developing countries has developed resistance against β-lactam antibiotics which are already in their fourth generation. The availability of a good quality three dimensional structure of target protein is necessary for the development of therapeutic drugs. A good quality three dimensional structure of Beta lactamase TEM-1 from S. typhi was not available. In this study, primary, secondary and tertiary structures of Beta lactamase TEM-1 from S. typhi were predicted using Expasy’s Protpram, PSIPRED and Homology modelling method respectively. The modelled structure was energy minimized and molecular dynamics and simulation studies were performed to investigate how the predicted model behaves structurally, dynamically
and thermodynamically using Gromacs 5.1 molecular dynamics and simulation tool. The structure was predicted to be fast attaining the normal temperature (300 K), pressure (1 Bar) and density (1000 Kg/m3) values during NVT (constant volume and normal temperature) and NPT (constant normal pressure and normal temperature) simulation steps within the given timeframe using OPLSAA
force field and SPC/E water model. The predicted structure was also validated using PROCHECK. The predicted model was found to be stereo-chemically stable in Ramachandran plot produced by PROCHECK as more than 93% residues were falling under core regions of the plot.
The structure will aid in discovery of more efficient alternative therapeutic drugs against typhoid
causing S. typhi.
TURKISH JOURNAL OF BIOLOGY, 2014
Inflammation can be broadly understood as a successive immune response of an organism's immune sy... more Inflammation can be broadly understood as a successive immune response of an organism's immune system towards nonnative or foreign antigens. This is a protective mechanism of the immune system, mediated by diverse immunological cells, to ensure homeostasis of an individual. Once activated, these immunological cells release a number of cytokines, chemokines, reactive oxygen species, reactive nitrogen species, histamines, prostaglandins, and other materials leading to inflammation. Tumor cells express altered proteins due to mutations of their genes, DNA modifications such as histone modification, DNA methylation, or other mechanisms of altered protein expression. The body's immunological cells actively recognize these altered proteins, now acting as tumor antigens, and eliminate the tumor cell; this is popularly known as tumor immunosurveillance. However, in unmanaged or inexorable circumstances, tumor cells escape from immunosurveillance mechanisms. This ultimately leads to the cascading events of cancer development and progression. T regulatory cells, tumor-associated macrophages, and myeloid-derived suppressor cells are pronounced cells involved in immunosuppression. These cells not only dodge the immune system's surveillance but also significantly increase the survival, proliferation, and metastasis rates of tumor cells. They hinder T cytotoxic activation by secreting inhibitory cytokines (which inhibit the antitumor activity of natural killer cells) along with dendritic cells and disrupt presentation of antigens, ultimately leading to cancer development. On their own, these cells have emerged as promising therapeutic targets in cancer immunotherapy. This review highlights some of the mechanisms by which these cells escape immunosurveillance and mediate immune suppression.
Chitinases occur in a wide range of organisms including bacteria, fungi, plants, insects, and ani... more Chitinases occur in a wide range of organisms including bacteria, fungi, plants, insects, and animals. Chitinase has been widely used as one of the mycobiocontrol agent as it degrades chitin which is a chain homopolymer of N- acetylglucosamine (GlcNAc) connected by β-1,4 glucosidic linkages. Beauveria bassiana is an insect pathogenic fungus successfully used as an insect pest control agent worldwide. In this paper, 21 different chitinase, endochitinase and chit proteins / gene retrieved from Swiss-Prot database are analysed and characterized. Various Bioinformatics and molecular modeling approach were adopted to explore properties and structure of chitinase gene in Entomopathogenic fungi. Primary structure analysis predicted the physico-chemical properties such as pI, EC, AI, GRAVY and instability index and provides data about these proteins and their properties. Subcellular localization were predicted by MultiLoc software. Prediction of motifs, patterns, disulfide bridges and secondary structure were performed for functional characterization. Three dimensional structures for chitinase like proteins are not available as yet at PDB. Therefore, homology models for were developed. The modelling of the three dimensional structure of these proteins shows that models generated by Modeller were more acceptable in comparison to that by Geno3D and Swiss Model.
The need for new and useful compounds to provide help and respite in all aspects of the human lif... more The need for new and useful compounds to provide help and respite in all aspects of the human life is always growing. It has
been well familiar that some plant pathogenic fungi can be developed as inundative biological control agents to kill or inhibit the activity of
some insects which cause a large destruction in the crop fields and in forest vegetation. Today, scientist worked on a number of fungi for
making it as a myco-insecticide because some fungi contain chitinase genes which degrade the outer hard cuticle of the insect pest.
Beauvaria bassiana is one of the fungi which is widely used in insect-pest control in forest as well as in crop fields. In the present study, DNA
of Beauvaria bassiana were extracted and amplified by PCR using designed primer from GeneRunner software for isolation of Bbchit1 gene.
Bbchit1 gene showed significant similarities with Cordyceps sp., Metarhizium , Trichoderma with endochitinase, chitinase and chit gene. The
sequencing of the gene was done and subjected to ClustalX for alignment to detect conserved region and a phylogenetic tree was also
generated. These results may be useful in characterizing the evolutionary mechanism of the species. The pathogenecity of the fungi was also
detected against insect larvae of Helicoverpa armigera on the basis of time and temperature. This study will facilitate the identification of virulence genes and the development of improved bio-control strains with customized properties.
Journal of Microbial & Biochemical Technology
Of late, nanotechnology has emerged to be a very reliable bridge in trying to club salient fields... more Of late, nanotechnology has emerged to be a very reliable bridge in trying to club salient fields of natural sciences on a common platform. Deservedly enough, nanomaterials have enabled numerous unconventional wonders to be accomplished through their incorporation, either on a singular or on complexed form. However, the rapid strides being accomplished on a tremendously high speed have sheerly ignored some ground realities in terms of ethical considerations. Bestowed with unconventional physicochemical properties and material behavior, nanomaterials are often surprise candidates in terms of their interaction with several other materials. This leads to a significant difficulty in the discard of integrated structures or individual materials carrying nanomaterials. The emerging threat of nanotoxicology from interactions thereof has attracted significant attention of environmental conservationists from the different corners of the world. In terms of physicochemical behavior, it is extre...