Pharmaceutical Sciences and Natural Products - Master Dissertation
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Item Antiproliferative activity of Asparagus racemosus extracts(Central University of Punjab, 2018) Sharma, Ram; Jaitak, VikasCancer 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.Item Synthesis of Benzazepinone Derivatives as Anticancer Agents(Central University of Punjab, 2018) P, Azhar Juman; Rao, Kaki VenkataCancer 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 activityItem Antiproliferative Activity of Chloroform and Methanol Extracts of Piper attenuatum (Buch-Ham)(Central University of Punjab, 2018) Pathak, Neha; Kumar, RajIndian 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.Item 3-D QSAR Study Of Combretastatins Fused With Hetrocyclic Ring As Tubulin Binding Agents(Central University of Punjab, 2018) Dhanka, Ajit Kumar; Kumar, VinodCombretastatin 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.Item Chemical Investigation and Antiproliferative screening of extracts from Stevia rebaudiana (Bertoni)(Central University of Punjab, 2018) Saxena, Aditi; Jaitak, VikasCancer 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.Item Synthesis and In Silico Studies Of Quinazolinone Derivatives As PARP-1 INHIBITORS(Central University of Punjab, 2018) Verma, Sonia; Kumar,PradeepCancer 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).Item Synthesis and in silico studies of pyrazoline containing quinoline derivatives as anti-HIV agents(Central University of Punjab, 2018) Choudhary, Diksha; Kumar,PradeepQuinoline 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.Item Synthesis And Biological Evaluation Of Pyrimidine Bridged Biphenyls As Putative Ligands To Target Parkinson's Disease(Central University of Punjab, 2018) Bala, Manu; Kumar, VinodMAO 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.Item Synthesis And Antiproliferative Activity Of Pyrazole-Based Heterocycles(Central University of Punjab, 2018) Pandey, Vishakha; Kumar, RajAmong 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.Item Phytochemical investigation of natural sweetener from stevia rebaudiana (Bartoni)(Central University of Punjab, 2014) Mayank; Jaitak, VikasS. rebaudiana is an important plant because of the high concentration of steviol glycosides (SGs). Sugars and artificial sweeteners, which are used in general as well as in pharmaceutical field have shown multiple toxic effects. On the other hand SGs have shown sweetness profile many fold compared to sucrose along with many health benefits.The substitution of SGs as sweeteners seems to be a reasonable solution towards the safety issues. The antidiabetic activity of S. rebaudiana extract as well as SGs is well documented in literature. The association of diabetes with cancer is also well known factor. Taking in consideration the above mentioned factors we have investigated the anticancer potential of extracts of S. rebaudiana. Extracts was prepared using petrolieum ether, ethyl acetate, methanol, aqueous methanol and water. Three cell lines (A-549, H-460 and MCF-7) have been used to evaluate the anticancer potential using MTT assay. In case of A-549, MVE-5 showing IC50 value of 10 ?g/ml. Moreover, IC50 values of MVE-2 was also comparatively better and found to be less than 50 ?g/ml and MVE-4 had shown IC50 value of 90 ?g/ml. In case of H- 460 reasonably better IC50 have been observed for MVE-4 and MVE-5 which is 88 ?g/ml and 92 ?g/ml, respectively. In H-460 reasonably better IC50 have been observed for MVE-4 and MVE-5 which is 88 ?g/ml and 92 ?g/ml, respectively. But in case of MCF-7 breast cancer cell line MVE-1 and MVE-2 have shown IC50 value of 90 ?g/ml and 53 ?g/ml, respectively. Thus, various extracts have shown good antiproliferative activity and S. rebaudiana can be further investigated for its anticancer potential. Furthermore docking study on EGFR, v PI3K and mTOR receptor revealed that SGs have good binding affinity towards all the three mentioned receptors and can be suitably modified to explore its anticancer potential. Moreover unfavourable 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 also been done successfully and total seven compounds have been isolated. Two compounds MVR-1 and MVR-5 have been successfully characterized and found to be quercetin and stevioside respectively which are already known compounds. Many reported SGs have shown poorer taste quality. Moreover taste quality of all SGs are different from one another. Thus docking studies were performed on SGs by constructing homology models of T1R2 and T1R3 subunits of human sweet taste receptors to explore the sweetness mechanism. Ramachandran plot, PROCHECK results and ERRAT overall quality factor indicated the acceptable quality of models. The binding pattern indicated that Asn 44, Ans 52, Ala 345, Pro 343, Ile 352, Gly 346, Gly 47, Ala 354, Ser 336, Thr 326 and Ser 329 are the main interacting amino acids residues of T1R2 and Arg 56, Glu105, Asp 215, Asp 216, Glu 148, Asp 258, Lys 255, Ser 104,Glu 217, Leu 51, Arg 52 of T1R3 respectively. Amino acids interact with SGs mainly by forming hydrogen bonds with hydroxyl group of glucose moieties. Maximum binding affinity has been obtained with SGs having total four glucose molecules attached with it and increase or decrease in glucose molecules reduced the binding afinityThere is significant variation in docked poses of all SGs. Taking in consideration the diverse binding patterns of various SGs as well as their structural features, we have proposed the mechanism of sweetness in the form of multiple point stimulation model. The present study will be helpful to know the proper mechanism of sweetness as well as binding patterns of SGs to sweet taste receptor. It will further helpful in understanding the difference in taste quality and will be used in improving the taste of SGs using semisynthetic approaches.Item Anticancer activity of cassia fistula linn through invitro and insilicoapproach(Central University of Punjab, 2014) Sharma, Akanksha; Jaitak, VikasCassia fistula L. (Leguminoseae) is a plant species called "Aragvadha" that means "disease killer". C. fistula consists of plethora of medicinal properties. A detailed discussion is depicted of the therapeutic potential and chemical composition of C. fistula that is responsible for its highly important medicinal properties. C. fistula contains many chemical components like anthraquinones, anthocyanindins, proanthocyanidins, flavanoids, polyphenols, alkaloids, saponins, coumarins, tannins, etc. These constituents are reported to possess various biological properties such as antioxidant, antimicrobial, antidiabetic, antitumor, antimelasmic activities etc. In the current dissertation work we limited our study to cancer; specifically, Lung cancer (LC) and Breast cancer (BC) which are spread all over the world to a threatening level. The present study is an effort to contribute to such a multi-targeting moiety from the plant C. fistula, on the basis of in vitro and simulated analysis. To explore the anticancer activity of C. fistula; in vitro (cytotoxicity studies) on different extracts and in silico studies using MMGBSA (Molecular Mechanics - the Generalized Born model and Solvent Accessibility) on the earlier reported molecules was performed; to study protein - ligand binding interactions on four different targets. The different extracts (Petroleum v ether (SVA-1) (for defatting), Ethyl acetate (SVA-2), Methanol (SVA-3), Hydro- methanolic (SVA-4) Extracts) were prepared in order of their increasing polarity. In- vitro cytotoxicity studies done using MTT (3-(4, 5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide) assay on the extracts of plant and their IC50 values were calculated. It was performed to identify plant's cytotoxic activity. Targets studied via performing in silico protein-ligand binding interactions of majorly mutated yet interlinked pathways of tyrosine kinase and serine/ threonine kinase family; that are namely EGFR, PI3K, Akt and mTOR receptors on which reported molecules of plant were studied. In silico studies were performed using maestro 9.6 Schrodinger software. MMGBSA and ADMET analysis were performed to discover and understand protein - ligand interactions between the chosen ligands of Cassia fistula and selected kinase receptors. On conducting MMGBSA (Molecular Mechanics ' the Generalized Born model and Solvent Accessibility) studies 5,3,4-tri-hydroxy-6-methoxy-7-O-?-L- rhamnopyranosyl-(1?2)-O-?-D-galactopyranoside along with few other moieties illustrated fine binding interactions against standard inhibitors of all the protein targets. From in vitro experiment, it was found that Hydromethanolic extract (SVA-4) showed prominent cytotoxicity against MCF-7, A-549 and H-460 cell lines particularly near 50?g/ml of concentration. Results were found in comparable with the NCI criteria limits for IC50 values of extracts obtained in assay. Also extracts were stable in DMSO solvent even when kept at the ambient temperature for 30 days and gave consistent results against cancer cell lines. As per the results of the in silico studies, the 5,3,4-tri- hydroxy-6-methoxy-7-O-?-L-rhamnopyranosyl-(1?2)-O-?-D-galactopyranoside (dG Bind score -98.7866kcal/mol) for EGFR in comparison to gefitinib (dG Bind score - 86.5585kcal/mol); (dG Bind score -87.3524kcal/mol) for Akt as compared to AZD 5363 (dG Bind score -76.5959); (dG Bind score -87.1051kcal/mol) for PI3K as compared to wortmannin (dG Bind score -79.0654kcal/mol) and for mTOR it has shown the (dG Bind score of -81.964kcal/mol) against sirolimus (dG Bind score -192.354kcal/mol) is reported to have fair pharmacokinetic profile along with attractive binding interactions with EGFR, PI3K, Akt and mTOR receptors.Item Design and synethesis of APE1 inhibitors as putative anticancer agents(Central University of Punjab, 2014) Kaur, Gagandeep; Kumar, RajSuccess in chemotherapy has not been attained completely yet and has remained a worried issue from years. Various reasons drive this failure, but the much talked about is failure due to emergence of resistance to chemotherapeutic drugs due to various factors. One of the major reasons here we have targeted is the resistance developed against DNA damaging chemotherapy due to over activation of APE1 enzyme evolved in BER pathway, which is the major repair pathway responsible for 95% of the DNA repair. Design and synthesis of APE1 inhibitors using rational approach fulfilling the pharmacophoric requirements has been carried out in this research work. Molecular modelling studies were performed to confirm that designed compounds fit well into the repair active cavity. 14 compounds have been designed and synthesized having pyrazolo-quinazolines core structure. The anticancer potential of the 8 representative compounds was evaluated against rat C-6 glial cell line at different concentrations. All synthesized compounds showed good anticancer activity against rat C-6 glial cell lines. The inhibitory potential of the compounds obtained from the MTT assay results helped us to formulate the SAR studies. Further ROS measurement was also carried out using DCFDA assay. Compounds showing good MTT results were also found to be potential antioxidants which conclude their mechanism of anticancer activity through APE1 inhibition. The active compounds may be taken further for lead optimisation and mechanistic interventions for their in vitro binding studies on APE1 in future.Item Design and synethesis of putative anti-cancer agents using hybrid molecular approach(Central University of Punjab, 2014) Saini, Vijayinder; Kumar, VinodA Hybrid drug involves the unification of two drug pharmacophores in one single molecule. The hybrid drugs are designed to interact with multiple targets or to intensify its effect through action on another bio target as one single molecule or to counterbalance the known side effects associated with the other hybrid part. One of the important role of hybrid drugs is to counter multidrug resistance. Muti-drug resistance observed during the treatment for cancer. Target therapy for various cancer are developed and successfully used to treat cancer patient. But treatment can be further strengthen by concurrent administration of single drug by combining two different drugs from different origin act at different receptor to cope MDR. It is also said as to load a multi-target drug in a single drug. In the current research proposal, we have designed and synthesized molecules which affect tubulin polymerization as well as MetAP-2 receptor. Both play vital role in tumor progression by strengthening the cell cytoskeleton and angiogenesis process respectively. The hybrids of chalcone (antitubulin) and arylazole (anti MetAP-2) were synthesized and molecular docking studies were performed. The compounds were synthesized by three step reaction and synthesized compounds were analyzed and confirmed by FTIR, NMR and mass spectrometry. The activity of synthesized compound was evaluated against HCT-116 (wild & null type) colon cancer cell lines at a concentration of 5 μM, 25 μM and 50 μM. Compounds were equally active in wild type and null type HTC-116 cell lines with slight less inhibition in null type. Lastly, the information on inhibitory potential of compounds v were obtained from MTT assay wherein VJ-4, VJ-2PP2 & VJ-4PP1 were found to be active anticancer agentsItem In vitro and In silico study of Essential oil Components from Eucalyptus tereticornis as Antibacterial agents(Central University of Punjab, 2018) Sharma, Anupama; Jaitak,VikasMany essential oils are known for their antimicrobial activity and the main target is bacterial cell membrane which is important for bacterial viability and hence the study was done to find the target and effective binding of the components of the Eucalyptus tereticornis essential oil and comparison with the standard drug used for in vitro and in silico studies, A/S combination. In vitro and In silico studies has shown the potential of Eucalyptus tereticornis essential oil in modulating antibacterial resistance and its potential as an antibacterial agent at a conc. of 10µl that was comparable with the standard and also at 50 µl, the zone of inhibition was found to be equivalent to that of standard combinational drug of A/S (10:10) mcg. The In silico studies further confirms its potential to combat antibacterial resistance as the docking results has shown the effective binding of the components of essential oil than the standard in the order ?-Terpinyl acetate (-2.754)> 8-epi-gama-eudermol> beta-eudesmol> L-alpha-Terpineol against PBP3 in comparison with the standard (-0.766). Docking simulation also suggests the effective binding of essential oil components with the beta lactamases as (-2.348) for Salbactam in comparison with (-3.671) Cis-p-mentha-1(7),8-dien-2-ol and also ADME/T studies has shown their ability to partition the bacterial cell membrane with logPo/w for the components for Aromadendrene (5.176), beta-myrcene (4.592). Along with 100% oral 6 absorption and the absorption through gut blood barrier QPPCaco found to be more than 500 for every component of the essential oil, and brain blood barrier that was found to be in range of 0.095 for alpha-terpinylacetate and 1.047 for Aromadendrene.Item Synthesis, Characterization and Biological Evaluation of 5-(2- Nitrophenyl)-1H-Pyrazole Derivatives as Putative Antiproliferative Agents(Central University of Punjab, 2018) Saini, Geetika; Kumar, RajPyrazoles 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 2Item Synthesis and Characterization of Pyridine and Pyrimidine Derivatives(Central University of Punjab, 2018) Ghosh, Desoshree; Venkata Rao,KakiPyridine and pyrimidine derivatives are important chemical compounds with tremendous biological applications. Fusion of pyrimidine moiety with different heterocycle scaffolds gives rise to a new class of hybrid heterocycles possessing improved activity. In our project work, we synthesized pyridine derivatives (Nicotinonitrile) and thieno[2,3-d]pyrimidine derivatives which may be further explored to generate novel compounds with several biological activities.Item Synethesis of some piperazine containing scataining scaffolds as potential MAO inhibitors(Central University of Punjab, 2014) Sheetal; Kumar,VinodFicus benghalensis and Ficus religiosa commonly known as Banyan and Peepal trees (or Bodhi) respectively, are important tropical trees that are being grown and traditionally revered throughout Indian subcontinent for thousands of years; however, DNA sequence-based genetic diversity of these trees are not yet known. In this report, phylogeography of these species using nuclear genome encoded ITS1-5.8S-ITS2 cistron, chloroplast genome encode RPS16- intron and trnL intron, and mitochondrial genome encoded COX1 gene is presented, making this one of the most comprehensive phylogenetic assessment of these trees conducted till date. Phylogeographic analysis of F. religiosa revealed a cryptic species, which later analysis confirmed as a novel species, described in this dissertation as Ficus indoensis Sp. Nov. that indicated affiliation to section Conosycea. Genetic heterogeneity of Ficus benghalensis remained very low and no apparent phylogeographic structures were detected. This study also revealed that colonies of Big Banyan tree at Adyar, Chennai, indeed are clonal, with 100% homology at all four loci investigated. Further, this investigation-having incorporated extensive taxa sampling (n=342) and four unlinked loci- resolved a number of phylogenetic structures within genus Ficus, so far the largest phylogenetic investigation conducted in this genus yet.Item Synthesis and characterization of 2-aminothiophene derivatives by Gewald reaction(Central University of Punjab, 2018) Pratibha, Agarwala; Venkata Rao, KakiSubstituted thiophene derivatives are very important heterocycles found in many biologically active and natural compounds. The Gewald multicomponent reaction was a remarkable discovery for the synthesis of wide variety of thiophene derivatives. Also the synthesis of the thieno pyrimidine derivatives as potential surrogates for this quinazoline core structure has, therefore, became a routine strategy in modern drug design and development. So we want do some multistep reaction to prepare thienopyrimidine derivative from thiophene which are very important core intermediates with various biological applications like anti-tumor, anti-bacterial, anti-microbial, anti-cancer agents.Item Phytochemical investigation and biological evaluation of secondary metabolites from asparagus racemosus l through in-vitro and in-silico approach(Central University of Punjab, 2013) Singla, Ramit; Jaitak, VikasNature has been a source of medicinal products for millennia, and with many useful drugs developed from different natural resources, with majority of drugs are from plant origin. Asparagus racemosus belonging to family liliaceae, is one such important medicinal plant. This plant species is used traditionally in India and other parts of the world in epilepsy, Vaat disorders, brain tonic, hypertension, hepatoprotection, immunostimulant and antiabortifacient. In this context, the aim of the present study was to explore the roots of A.racemosus in terms of its medicinal values for instances antimutagenic, and advanced glycation end-product inhibitor. Antimutagenic activity of different extracts were evaluated using Ames test. A. racemosus methanolic extract (RME) and aqueous extract (RAE) have been found to have effective in the inhibition mutation induced by NPD and sodium azide. Among the two extracts, RAE and RME showed maximum inhibition of 49.2%, and 40.63% in Co-incubation mode respectively. The inhibition of BSA-glucose for the determination of antiglycation activity showed that the inhibition varied significantly among different extracts of A. racemosus. The highest inhibition measured by BSA-glucose was observed for (Ethyl acetate extract) REE (IC50 37.56 ± 1.65 ?g/mL) followed by (methanolic extract) RME (IC50 51.32 ± 1.48 ?g/mL). Isolation of molecules from methanol extract led to the characterisation of one molecule v namely nyasol out of total seven isolated molecules. The molecular docking study of isolated molecule Nyasol displayed strong binding affinity with estrogen receptor ? and estrogen receptor ?, indicating that Nyasol is beneficial in hormone responsive breast cancer. Moreover, in-silico study of already reported phytoestrogens from A.racemosus was also carried out using Glide docking to investigate interaction pattern with Human placental estrone sulphatases (1P49), human 17?-hydroxysteroid-dehydrogenase type 1 (1FDS), human glucose 6-phosphate dehydrogenase (2BH9) and tubulin protein receptors. The top docking score was obtained for rutin (estrogen receptor ?), 3,6,4'-trimethoxy-7-O-?-D-glucopyranosyl [1?4]-O-?-D-xylopyranoside glucopyranpsyl (HSP90), 8-Methoxy-5,6,4-trihydroxyisoflavone-7-O-?-D-glucopyranoside (human placental estrone sulphatase), Shatavarin X (17?-hydroxydehydrogenase`), Racemoside A (Glucose-6-phosphate dehydrogenase), Immunoside (Colchicine binding site of tubulin). The results indicated that phytoestrogens are likely potential candidate for controlling tumor progression with a special emphasis in breast cancer progression.Item Phytochemical investigation in vitro anti-mutagenic activity of potentilla fulgens lodd and silico study of flavonoids with CDK-2,CDK-6 receptors(Central University of Punjab, 2013) Monga, Prakriti; Jaitak, VikasPlants have been used for thousand years in the treatment of various diseases. Plant secondary metabolites have proved to be an excellent source of new medicinal compounds. They offer protection against variety of chronic diseases including diabetes, cardiovascular diseases, obesity and cancer. Mutation is an important factor that is linked to carcinogenesis. It has been found that occurrence of cancer can be reduced by decreasing the incidence or rate of mutation. Plants are promising source of antimutagens agents which are present in them as secondary metabolites such as flavonoids, alkaloids, terpenoids, glycosides etc. Potentilla fulgens is an important medicinal plant of higher Himalayas that is known globally for its therapeutic importance. A number of antioxidant constituents have been reported from the plant which mainly consists of polyphenolic compounds. It has been observed that diet rich in polyphenolic compounds such as flavonoids can reduce the risk of cancer. P.fulgens reported to have polyphenolic compounds such as flavonoids which are potent bioactive molecules that possess anticarcinogenic effects as they can interfere with initiation, development and progression of cancer by the modulation of cell cycle, apoptosis, and angiogenesis. Anti-mutagenic activity on different fractions of P.fulgens was carried out, which indicates that n-butanol and water fractions of the plant are strongly anti-mutagenic. Inhibitory activity for n-butanol fraction was 60.4% and 35.4% in co-incubation and pre-incubation respectively in TA 98 tester strains while 55.6% and 62.0% inhibition was observed in TA100 tester strains respectively for co and pre-incubation. For water fraction 56.6% and 60.7% inhibitory activity in co-incubation and pre-incubation mode of treatment respectively against TA98 strain and 34.5% and 50.6% inhibition in TA100 strain for co-incubation and pre-incubation treatment respectively. Results specify the importance of P.fulgens as a new source of anti-mutagenic agents. Isolation of molecules from ethyl acetate and n-butanol v fractions led to the characterisation of one molecule namely catechin out of total six isolated molecules. In-silico study of various reported flavonoids were performed on CDK-2, CDK-6 as these receptors are linked to cell cycle and mutation in cell cycle may lead to cancer. In-silico study indicates that natural as well as synthetic flavonoid molecules can be considered as a treatment for cancer by inhibiting CDK-2 and CDK-6 receptors.