Pharmaceutical Sciences and Natural Products - Master Dissertation

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

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Anticancer potential of new n-acetyl pyrazoline derivatives of 1,3 diaryl/hetroaryl propenoes: Synethesis and evaluation
(Central University of Punjab, 2013) Alex, Jimi Martin; Kumar, Raj
Pyrazoles, categorized as nitrogen-containing heterocycles, are well known for their interminable participation in the field of perpetual research and development of therapeutical active agents. As a consequence pyrazoles became an inevitable core of numerous drugs having diverse activities. The broad spectrum of activities portrayed by the pyrazoles instigated the researchers to modify the pyrazole ring as 4,5-dihydro-1H-pyrazoles commonly known as 2-pyrazolines. This modification played a determining role in defining the biological activities of several compounds. The presence of aromatic/heterocyclic substituents on the pyrazoline ring only served to accentuate these activities. Literature survey also revealed that substitution such as amide group, acetyl groupetc.at N1 of the pyrazoline also played a decisive role in deciding the biological activity. The vast information obtained from literature survey stimulated us to synthesize compounds having 2-pyrazoline as the core moiety of which either the C3 or C5 was substituted with heterocyclic ring in addition to acetyl moiety at the N1 of the pyrazoline. The compounds were assessed for their anticancer potential against four cancer cell- MCF-7, H-460, T-47 D and A-549. MTT assay was carried out for testing the cell viability. The assay results revealed that certain compounds showed anticancer potential because these agents inhibited the proliferation of breast cancer cell lines but not against lung cancer cell line. Compounds showing good activity against the cancer cell lines were also evaluated for their antioxidant property especially against reactive oxygen species
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.
Design and synethesis of APE1 inhibitors as putative anticancer agents
(Central University of Punjab, 2014) Kaur, Gagandeep; Kumar, Raj
Success 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.
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.
Synethesis and biochemical screening of novel non-purine based xanthine oxidase inhibitors
(Central University of Punjab, 2013) Kumar, Deependra; Kumar, Raj
Xanthine oxidase (XO), or xanthine oxidoreductase (XOR), is a complex molybdoflavoenzyme which, in humans, is recognized as the terminal enzyme of purine catabolism, catalysing the hydroxylation of purines to uric acid, overproduction of which usually leads to a pathological condition called hyperuricemia and gout. XO inhibitors (XOI) are proved to be promising urate lowering agents. Purine based XOI (allopurinol) however, are associated with various lethal side effects like hypersensitivity syndrome (Stevens Johnson syndrome and Tissue Epidermal Necrolysis), bone marrow depression, rash etc. On the other hand non-purine based XOI (febuxostat) are found to be safer and effective antihyperuricemic and antigout agents. Present investigation describes synthesis, characterization of some non-purine based compounds and their evaluation for xanthine oxidase inhibitory activity
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.
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