Pharmaceutical Sciences and Natural Products - Master Dissertation

Permanent URI for this collectionhttps://kr.cup.edu.in/handle/32116/53

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Start date: 2013End date: 2018

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    Synthesis of Benzazepinone Derivatives as Anticancer Agents
    (Central University of Punjab, 2018) P, Azhar Juman; Rao, Kaki Venkata
    Cancer is a disease which starts uncontrolled development of cell as it loses its essential structure and usefulness and that may go ahead to assault and destroy neighboring tissues. Cyclin dependent kinase have major role in control of cell cycle, emphasize their significance as anti-cancer drug targets. Kenpaullone and hymenialdisine are previously reported as potent inhibitors of CDKs with a notable seven membered lactam scaffold. In our research work we synthesized benzazepinone based novel compounds with seven-membered lactam pharmacophore by Fischer indole synthesis and Claisen-Schmidt condensation reactions. Molecular docking study of the synthesized compounds was conducted for understanding the interaction pattern of compounds with CDK2 binding sites which involved in cancer. All synthesized benzazepinone derivatives were having best dock score at the CDK2 binding site and have better G score. Due to the perfect binding interaction of benzazepinone derivatives with CDK2, in future the synthesized molecules will be useful for further testing for evaluating their anticancer activity
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    Antiproliferative activity of Asparagus racemosus extracts
    (Central University of Punjab, 2018) Sharma, Ram; Jaitak, Vikas
    Cancer is regarded as uncontrolled progression and spread of cells. Cancer is not a singular, specific disease but a group of variable tissue responses that result in uncontrolled cell growth. Healthy cells have a specific size, structure, function and growth rate that best serves the needs of the tissues they compose. Cancer is one of the leading of morbidity and mortality worldwide, with approximately 14 million new cases in 2017. Breast cancer (BC) is a disease where cells in the tissue of the breast cancer grow and divide without normal control. Estrogen receptor is a group of proteins (or a twelve helix protein) present inside the cells of the female reproductive tissues or located in the nucleus of cells. ER?, ER? and ER gamma have different responses and they are located in different tissues. Quinone forms of catechol estrogen binds to DNA and forms adduct. Semi Quinone intermediates are free radicals can bind with oxygen to producing superoxide radicals. Superoxide radicals can attack and alter the structure of DNA and causing Breast cancer. Various synthetic drugs (Tamoxifen & Raloxifene) are used for treatment of breast cancer, but numerous side effects like menopausal symptoms, vaginal dryness, low libido, mood swings and Nausea. The discovery of novel natural drugs is important for reduction of side-effects, high selectivity, low toxicity, and better killing of cancer cells. Phytoestrogens are one the best category of natural products used for treatment of breast cancer. Phytoestrogens have similar structure to the endogenous estrogen. Distance between the hydroxyl groups is 14.5 A0 is similar to estrogen. Asparagus racemosus contain large number of phytoestrogens. In this context, the aim of the present study was to explore the roots of Asparagus racemosus in the terms of its medicinal values for Breast cancer. Anticancer activity of different extracts were evaluated by performing In vitro study by using Breast cancer cell lines T-47 D. from the Preliminary phytochemical investigation of extracts demonstrated that methanolic extract and Aqueous methanolic extract contain large number of phytoestrogens. Aqueous methanolic extract and methanolic extract showed maximum IC50 value as compare to other extract. Isolation of molecules from methanol extract, total four molecules isolated from methanol extract and three molecules from aqueous methanol extract. Moreover, in silico study of reported phytoestrogen from Asparagus racemosus was also carried out using glide docking to investigate interaction pattern with estrogen receptor ? and estrogen receptor ?. The top docking score was obtained for Rutin (Estrogen receptor ?) and Quercetin (Estrogen receptor ?). Tamoxifen and raloxifene used as standard for estrogen receptor ? and oestradiol used as standard for estrogen receptor ?. From the ADME study demonstrated that maximum flavonoids has highest oral absorption as compare to other. The results showed that phytoestrogens are expected prospective candidate for regulatory tumor progression with a special emphasis in breast cancer progression.
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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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    Chemical Investigation and Antiproliferative screening of extracts from Stevia rebaudiana (Bertoni)
    (Central University of Punjab, 2018) Saxena, Aditi; Jaitak, Vikas
    Cancer is the uncontrolled development of abnormal cells in the body. It is considered as the leading public health problem in both developed and the developing countries. As no drug of cancer is establish to be completely efficient and safe as anticancer therapy and is responsible for the prolonged toxicity and also causes various side effects. Chemoprevention of cancer by natural products is beneficial, as these compounds have the nominal side effects and short of toxicity compared to the synthetic compounds. The phenomena of Carcinogenesis is very complex and includes so many signaling pathways. Thus Phytochemicals are measured as the right candidates for developing the anticancer drug. The study for developing more potent candidates which can obstruct or slow down the expansion of the cancer cells without c au s in g any side effects from these phytochemicals are still in progress and Many new phytochemicals and its derived analogs have been recognized as potential candidates for anticancer therapy among these one of the potent plant is Stevia rebaudiana. The leaves of Stevia rebaudiana tends to possess zero calories, and consists mainly of ent kaurene diterpene glycosides generally recognized as steviol glycosides. Stevioside is the main sweet component found in S. rebaudiana. studies suggest that the stevioside along with v other associated compounds including rebaudioside A, steviol, and isosteviol tends to have therapeutic benefits including anticancer activity. Taking in consideration the above mentioned factors we have investigated the Anticancer potential of extracts of S. rebaudiana. Four extracts was prepared using petroleum ether, chloroform, ethyl acetate and aqueous methanol. T47D cell line have been used to evaluate the anticancer potential using MTT assay. AD-2 that is chloroform extract showing IC50 value of 7.79μg/ml. Moreover IC50 value of AD-4 that is aqueous methanol was also comparatively better and found to be 9.53 μg/ml and AD-1 that is petroleum ether had shown IC50 value of 9.58μg/ml. Thus, various extracts have shown good Antiproliferative activity and S. rebaudiana can be further investigated for its anticancer potential. Furthermore docking study on estrogen receptor–alpha, androgen receptor and aromatase receptor discovered that the phytochemicals of the plant have good binding affinity towards all the three mentioned receptors and can be suitably customized to search its anticancer potential. Moreover unfavorable ADME profile can be overcome by structure modification. Thus on the basis of in-vitro and in-silico data we can conclude that S. rebaudiana extracts have promising anticancer potential. further isolation of compounds have been done successfully and total four compounds have been isolated. two compounds ASP-2 and ASP-4 have been successfully characterized and found to be Stevioside and Rebaudioside A respectively which are already known compounds.
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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 Biological Evaluation Of Pyrimidine Bridged Biphenyls As Putative Ligands To Target Parkinson's Disease
    (Central University of Punjab, 2018) Bala, Manu; Kumar, Vinod
    MAO inhibitors have been explored as therapeutic agents for the treatment or management of PD. A series of 2,4,6-trisubstituted pyrimidine derivatives incorporating a propargyl moiety were synthesized and screened for their MAO inhibition potential using Amplex® Red assay. All the compounds showed good inhibitory activity for MAO-B. The structure-activity relationship profile has been developed with number of electron releasing and electron withdrawing substituents attached to the pyrimidine nucleus. MV7 was found to be the most potent MAO-B inhibitor with IC50 value of 0.44 ± 0.02 ?M. From molecular docking studies, it was found that compounds fit well in the active site of MAO-B isoform near FAD cofactor. Thus, the active compound MV7 obtained in this series can act as promising lead for the development of effective and potent MAO-B inhibitor for the treatment of Parkinson's disease.
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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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    3-D QSAR Study Of Combretastatins Fused With Hetrocyclic Ring As Tubulin Binding Agents
    (Central University of Punjab, 2018) Dhanka, Ajit Kumar; Kumar, Vinod
    Combretastatin A4 (CA4) is a leading agent in vascular disrupting strategies and tubulin polymerization inhibitor for the tumour therapy. A large number of combretastatin derivatives have been synthesized as potent inhibitors of Tubulin which are responsible for the anticancer activity. Combretastatins bind with the colchicine binding site of the tubulin and disrupt the dynamic equilibrium of tubulin. IN the current research proposal we have performed 3D-Field based QSAR on Combretastatins analogue in order to recognize structural features which are responsible for the tubulin inhibitors activity. The designed compounds are expected to show good inhibitory activity against tubulin when electrostatic group is attached in case of compounds 16 and 18, Bulky group is attached in case of compound 26 and hydrophobic group is attached in case of compound 51 respectively.
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    Synthesis and in silico studies of pyrazoline containing quinoline derivatives as anti-HIV agents
    (Central University of Punjab, 2018) Choudhary, Diksha; Kumar,Pradeep
    Quinoline moiety is an important scaffold in the field of drug discovery and drug development with wide range of pharmacological activities. Its derivatives are potent inhibitors for reverse transcriptase which is responsible for the conversion of single strand viral RNA into double strand viral DNA. In the present study, we have designed and synthesized Pyrazoline containing quinoline derivatives as anti-HIV agents. Six compounds were synthesized and characterized by 1H and 13C NMR and Mass spectrophotometry. The synthesized compounds were also docked on HIV binding site (PDB: 4I2P) and most of these showed good binding interactions with the active domain of the receptor. Our synthesized compounds DC1 and DC6 showed better binding interactions as compared to standard inhibitor Elvitegravir.
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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