School Of Basic And Applied Sciences

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Subject: search.filters.subject.Antiproliferative

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Now showing 1 - 6 of 6
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    Design, synthesis and evaluation of 4-phenyl-1,2,3-triazole substituted pyrimidine derivatives as antiproliferative and tubulin polymerization inhibitors
    (Elsevier B.V., 2022-06-26T00:00:00) Dwivedi, Ashish Ranjan; Kumar, Vijay; Yadav, Ravi Prakash; Kumar, Naveen; Jangid, Kailash; Anand, Piyush; Sharma, Deepak Kumar; Barnawal, Somesh; Kumar, Vinod
    Ligands binding to the colchicine domain of the tubulin protein act as tubulin polymerization inhibitors and arrest the cell cycle in G2/M phase. A series of 4-Phenyl-1,2,3-triazole substituted pyrimidine derivatives have been synthesized and evaluated for antiproliferative and antitubulin activities. In the series, AV-6 and AV-14 were found to be active against the three tested cancer cell lines wherein AV-6 displayed IC50 values of 1.2 �M, 5.5 �M, and 1.9 �M while AV-14 displayed IC50 values of 4.7 �M, 1.7 �M, and 1.4 �M against HCT-116, MCF-7 and HT-29 cell lines, respectively. These compounds were found to be non toxic to the normal cells (HEK-293). In the cell cycle analysis and JC-1 studies, these compounds induce mitocondria mediated apoptosis. In the tubulin polymerization inhibition studies, AV-6 displayed significant tubulin polymerization inhibition potential. In the molecular docking and simulation studies, these compounds fit well in the active site of colchicine. � 2022 Elsevier B.V.
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    Synthesis and screening of novel 4-N-heterocyclic-2-aryl-6,7,8-trimethoxyquinazolines as antiproliferative and tubulin polymerization inhibitors
    (Elsevier Ltd, 2022-08-28T00:00:00) Dwivedi, Ashish Ranjan; Rawat, Suraj Singh; Kumar, Vijay; Kumar, Naveen; Anand, Piyush; Yadav, Ravi Prakash; Baranwal, Somesh; Prasad, Amit; Kumar, Vinod
    Colchicine binding site represent a crucial target for the anticancer drug development especially in view of emerging drug resistance from the currently available chemotherapeutics. A total of 16 novel 4-N-heterocyclic-2-aryl-6,7,8-trimethoxyquinazolines were synthesized and screened for antiproliferative and tubulin polymerization inhibition potential. The synthesized compounds were evaluated against MCF-7, HeLa and HT-29 cancer cell lines and normal cell line HEK-293 T. In the series, 2?aryl group with 4?bromophenyl substitution displayed IC50 values of 6.37 �M, 17.43 �M, 6.76 �M and 4?chlorophenyl substitution displayed IC50 values of 2.16 �M, 8.53 �M, 10.42 �M against MCF-7, HELA and HT29 cancer cell lines, respectively. In the mechanistic studies involving cell cycle analysis, apoptosis assay and JC-1 studies, both the lead compounds were found to induce mitochondria mediated apoptosis and lead molecule with 4?chlorophenyl substitution displayed significant tubulin polymerization inhibition activity. In the computation studies, lead molecule displayed significant binding affinites in the colchicine domain and showed good thermodynamic stability during 100 ns MD simulation studies. 4-N-Heterocyclic-2-aryl-6,7,8-trimethoxyquinazolines showed appreciable drug like characteristics and can be developed as potent anticancer agents. � 2022 Elsevier Ltd
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    Synthesis and screening of novel 4-N-heterocyclic-2-aryl-6,7,8-trimethoxyquinazolines as antiproliferative and tubulin polymerization inhibitors
    (Elsevier Ltd, 2022-08-28T00:00:00) Dwivedi, Ashish Ranjan; Rawat, Suraj Singh; Kumar, Vijay; Kumar, Naveen; Anand, Piyush; Yadav, Ravi Prakash; Baranwal, Somesh; Prasad, Amit; Kumar, Vinod
    Colchicine binding site represent a crucial target for the anticancer drug development especially in view of emerging drug resistance from the currently available chemotherapeutics. A total of 16 novel 4-N-heterocyclic-2-aryl-6,7,8-trimethoxyquinazolines were synthesized and screened for antiproliferative and tubulin polymerization inhibition potential. The synthesized compounds were evaluated against MCF-7, HeLa and HT-29 cancer cell lines and normal cell line HEK-293 T. In the series, 2?aryl group with 4?bromophenyl substitution displayed IC50 values of 6.37 �M, 17.43 �M, 6.76 �M and 4?chlorophenyl substitution displayed IC50 values of 2.16 �M, 8.53 �M, 10.42 �M against MCF-7, HELA and HT29 cancer cell lines, respectively. In the mechanistic studies involving cell cycle analysis, apoptosis assay and JC-1 studies, both the lead compounds were found to induce mitochondria mediated apoptosis and lead molecule with 4?chlorophenyl substitution displayed significant tubulin polymerization inhibition activity. In the computation studies, lead molecule displayed significant binding affinites in the colchicine domain and showed good thermodynamic stability during 100 ns MD simulation studies. 4-N-Heterocyclic-2-aryl-6,7,8-trimethoxyquinazolines showed appreciable drug like characteristics and can be developed as potent anticancer agents. � 2022 Elsevier Ltd
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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, 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