Master's Dissertations

Permanent URI for this collectionhttps://kr.cup.edu.in/handle/32116/156

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Subject: search.filters.subject.Cancer

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Now showing 1 - 9 of 9
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    Synthesis and In Silico Studies Of Quinazolinone Derivatives As PARP-1 INHIBITORS
    (Central University of Punjab, 2018) Verma, Sonia; Kumar,Pradeep
    Cancer is one of the leading diseases responsible for high mortality rates worldwide. It develops when normal cells begin to grow out of control in particular part of the body. Cancer is a leading cause of death worldwide, accounting for 8.8 million deaths in 2015. According to WHO, the most common causes of cancer death are cancers of Lung (1.69 million deaths), Liver (788 000 deaths), Colorectal (774 000 deaths), Stomach (754 000 deaths) and Breast (571 000 deaths). PARP-1 is a ubiquitous zincfinger DNA-binding enzyme that is activated by binding to DNA breaks and then catalyzes the synthesis of the branched polymer PAR using NAD+ as the building block. PARP-1 has a crucial role in cell proliferation, survival, and death, due to its properties on regulation of multiple biological processes. Quinazolinone and its derivatives possess a large class of biologically active compounds that exhibited broad spectrum of biological activities such as anti-HIV, anticancer, antifungal, antibacterial, anticonvulsant, anti-inflammatory, antidepressant, antimalarial, antioxidant, antileukemic, and antileishmanial activities and other activities. In this study, we have synthesized quinazolinone derivatives and studied the in silico properties as PARP-1 inhibitors which indicated that quinazolinone derivatives were having good affinity towards active site of PARP-1. Out of all synthesized compounds, SVA-11 was having maximum dock score (-10.421).
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    Impact of mitochondrial transplantation on cancer cells
    (Central University of Punjab, 2014) Aggarwal, Alza; Bhardwaj, Pankaj
    Mitochondria, the powerhouse of the cell, are small granular or filamentous bodies associated significantly with cellular respiration and are the main sources of energy, due to which they are present in maximum number in the organs that require large amounts of energy for doing their function like muscle cells, neural cells, etc. In case of any dysfunction of mitochondria, these organs are most affected culminating in a number of serious multi organs diseases, irrespective of age such as neurogenic weakness with ataxia and retinitis pigmentosa (NARP), or Leigh syndrome (LS), Cancer, etc. Although mutations in mitochondrial genes are common in cancer cells, they do not inactivate mitochondrial energy metabolism, but rather alter the mitochondrial bioenergetics and biosynthetic state. Literature survey also revealed that owing to mitochondrial dysfunction the clinical trial of many anticancer drugs has failed in patients. This study is focused on the impact of mitochondrial transplantation on cancer cells and their drug sensitivity against four human cancer cell lines HCT116 (WT & P53mutated), HepG2 and MCF7. The normal cell's Mitochondria was transplanted into cancer cells and then evaluated the Impact of transplantation of mitochondria from healthy cells into cancer cell upon their growth, ROS production and their drug sensitivity. The results of this study revealed that the healthy mitochondria transplanted to cancer cells decrease carcinogenesis and have drug sensitivity. So, it may be used as futuristic cancer remedy.
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    Antiproliferative Activity of Chloroform and Methanol Extracts of Piper attenuatum (Buch-Ham)
    (Central University of Punjab, 2018) Pathak, Neha; Kumar, Raj
    Indian traditional medicinal plant Piper attenuatum (Buch-Ham) has been investigated for its antiproliferative activity. Dried powder of fruits of Piper attenuatum (Buch-Ham) was subjected to maceration to prepare various extracts using different solvents in the order of increasing polarity. In vitro antiproliferative activity of all the extract was carried out using MTT assay against MDA-MB-231(Breast cancer) cell line. The Chloroform and Methanol extracts were found to be the most active fractions. The results from MTT assay of isolated compounds from Chloroform extract, NP7C was found to be the most potent antiproliferative agent with IC50 value of 3.83 ?M which is comparable to etoposide 2.37 ?M. Compound NP7L also exhibit significant antiproliferative activity (IC50 of 6.44 ?M) which was comparable to colchicine (IC50 = 6.3 ?M). Thus, the present study indicated that isolated compounds of Piper attenuatum (Buch-Ham) possess great potential to be developed as anticancer agent in future.
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    Synthesis And Antiproliferative Activity Of Pyrazole-Based Heterocycles
    (Central University of Punjab, 2018) Pandey, Vishakha; Kumar, Raj
    Among the various heterocyclic compounds pyrazole and its derivatives have occupied wide range of biological and pharmacological activities. These were observed for their modes of function in the inhibition of topoisomerase and DNA repair. DNA topoisomerases usually modify DNA topology by their ability to break and reseals both its strands. Which were leads to DNA replication, transcription processes. It helps as a vital targets for numerous chemotherapeutic agents. The potency of topoisomerase inhibitors looks to be diminishing due to drug resistance and lack of efficacy. Thus, after long glimpsing the current scenario was made in order to develop topoisomerase inhibitors with completely new scaffold or alteration or modification in the existing scaffold. We herein report design and synthesis of pyrazole based compounds as topoisomerase inhibitors. The synthetics were evaluated for their in vitro anticancer activity against MDAMB 231 breast cancer cell line.
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    Synthesis, Characterization and Biological Evaluation of 5-(2- Nitrophenyl)-1H-Pyrazole Derivatives as Putative Antiproliferative Agents
    (Central University of Punjab, 2018) Saini, Geetika; Kumar, Raj
    Pyrazoles are known to exhibit various biological activities like antibacterial, antiprotozoal, anticonvulsant, analgesic, anti-inflammatory, antiviral and antiproliferative. An attempt has been made to synthesize substituted pyrazoles. Their antiproliferative activity was determined by performing MTT assay on MDA-MB 231 cell line (breast cancer). The compounds were further docked into topoisomerase 1 and 2
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    Imidazole based compunds: Synethesis and in vitro anticancer screening
    (Central University of Punjab, 2013) Negi, Arvind; Kumar, Raj
    Imidazole is an important five-membered aromatic heterocycle widely present in natural products and synthetic molecules. The unique structural feature of imidazole ring with desirable electron rich characteristic is beneficial for imidazole derivatives to readily bind with a variety of enzymes and receptors in biological systems through diverse weak interactions, thereby exhibiting broad bioactivities. Numerous imidazole-based compounds are in being used extensively in the clinics to treat various types of diseases. We have synthesized, designed and evaluated imidazole-based compounds for anti-proliferative activity against A-549 and Hep-G2 human cancer cell lines. Further the free radical scavenging activity of the selected compounds was performed in order to observe their antioxidant potential (if any). The combined results have shown advent of their first in vitro bioactivity as anticancer and antioxidant compounds and revealed their medicinal potential. The synthetics offer the scope for generation of a library of compounds and their evaluation against a panel of cancer cell lines, studies on structure activity relationship, tracing their molecular mechanism(s) in addition to their development at preclinical level in future.
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    Potential Mitochondrial-Specific Function Of piRNAs
    (Central University of Punjab, 2018) Paul, Shouvik; Singh, Sandeep
    Piwi-interacting RNAs (piRNAs) are (26-31 nt) small noncoding RNAs processed from their longer precursor transcripts with the help of Piwi proteins. There are more than 30,000 piRNA genes present in the human genome which now turns out to be emerging player in both homeostasis and diseases. Localization of piRNA and PIWI in the repeat region of the mammalian nuclear genome in germ cells has been reported, although localization and potential functional role of piRNA in the mammalian mitochondrial genome are largely unknown. We have taken 111 piRNA sequences found in the MCF-7 mitochondrial genome, which is obtained by NGS analysis for alignment study. Resulting piRNA have been aligned with DQ112870 North American Homo sapiens mitochondrion genome for studying post- transcriptional roles of piRNA.
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    Generation of Rho-0 Cells using MDA-MB-231 Cell Line and Measurement of Drug Cytotoxicity
    (Central University of Punjab, 2018) Sharma, Bharti; Singh,Sandeep
    The ATP generation via Oxidative phosphorylation (OXPHOS) system located in the inner membrane of mitochondria, is regulated by the coordinated interaction between nucleus and mitochondria. In the same context, mitochondrial-depleted cell (Rho-0) can be a helpful approach to study the mitochondrial metabolism, mitochondrial role in various cellular processes such as apoptosis, mitochondrial role in various mitochondrial related disorders and cancer. To generate Rho-0 cells, EtBr mediated mtDNA depletion was done and verified by agarose gel electrophoresis. % cell viability, mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) production was measured after 24 hr treatment with 3 drugs, ?-amanitin, Doxorubicin and DCA in both parental MDA-MB-231 and Rho-0 cells. Reduced cell death and ROS production was observed in Rho-0 cells indicating the resistance against apoptosis in Rho-0 cells and demonstrating the possible role of mitochondria in intrinsic pathway of apoptosis. MMP was observed to be maintained in Rho-0 cells indicating the role of nuclear genome in the maintenance of MMP.
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    Study the effect of phytochemicals phenethyl isothiocyanate (PEITC) and Quercetin on mitochondrial biogenesis in cancer and normal cell lines
    (Central University of Punjab, 2018) Thakur, Anchal; Chander, Harish
    Phytochemicals are plant-derived chemicals generally are biologically active compounds and mediate positive health benefits by targeting genes or metabolic pathways of a cell. The phytochemicals examined can be classified into main categories, such as carotenoids and polyphenols, which include phenolic acids, flavonoids and stilbenes / lignans. Quercetin is isolated from the Tridax procumbens (Linn.). Its anti-cancer activity has been well documented in vitro and in vivo. It could be pro-apoptotic as well as anti-apoptotic depending upon its concentration of it and time of exposure. Isothiocyanates are cruciferous derived phytochemicals. PEITC majorly isolated from Nasturtium officinale (watercress) has shown to mediate its anti-cancer activity through ROS-mediated pathway. It is a basic leucine zipper protein involved in protection against oxidative damage triggered by stress like injury or inflammation through regulation of the expression of anti- oxidant proteins. Under oxidative stress, inactivation of Kelch-like ECH-associated protein 1 (Keap1) occurs which is a cytosolic repressor protein that binds to Nrf2. This results in Nrf2-Keap1 complex dissociation, and hence, promoting the translocation of Nrf2 to the v nucleus where it binds to ARE (anti-oxidant response element), and induce the transcription of anti-oxidative proteins. Quercetin and PEITC treatment to the cancer cells led to decreased mitochondrial biogenesis as the NRF-2 levels diminishes as the concentration of the drug increases. The anti-oxidant levels are getting down in the cancer cells leading to ROS accumulation in the cancer cells leading ultimately to the death. Quercetin and PEITC treatment to the normal HBL-100 cells induced the mitochondrial biogenesis by increasing NRF-2 levels as the concentration of the drug increases. Confocal microscopy results also proved that treatment of quercetin or PEITC or the combination of both drugs was found to be effective in cancer cells as the mitochondria size and shape got decreased interpreted through the intensity of green dye. To conclude our study, it has been shown that quercetin and PEITC lead to increased mitochondrial biogenesis in normal cells whereas decreased mitochondrial biogenesis in cancer cells.