School Of Basic And Applied Sciences

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Subject: search.filters.subject.Estrogen receptor

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    Synthesis, in vitro, and docking analysis of c-3 substituted coumarin analogues as anticancer agents
    (Bentham Science Publishers, 2020-01-28T00:00:00) Thakur, Anuradha; Kaur, Kamalpreet; Sharma, Praveen; Singla, Ramit; Singh, Sandeep; Jaitak, Vikas
    Background: Breast cancer (BC) is a leading cause of cancer-related deaths in women next to skin cancer. Estrogen receptors (ERs) play an important role in the progression of BC. Current anticancer agents have several drawbacks such as serious side effects and the emergence of resistance to chemotherapeutic drugs. As coumarins possess minimum side effects along with multidrug reversal activity, it has a tremendous ability to regulate a diverse range of cellular pathways that can be explored for selective anticancer activity. Objectives: Synthesis and evaluation of new coumarin analogues for anti-proliferative activity on human breast cancer cell line MCF-7 along with exploration of binding interaction of the compounds for ER-? target protein by molecular docking. Methods: In this study, the anti-proliferative activity of C-3 substituted coumarins analogues (1-17) has been evaluated against estrogen receptor-positive MCF-7 breast cancer cell lines. Molecular interactions and ADME study of the compounds were analyzed by using Schrodinger software. Results: Among the synthesized analogues, 12 and 13 show good antiproliferative activity with IC50 values 1 and 1.3 ?M, respectively. Molecular docking suggests a remarkable binding pose of all the seventeen compounds. Compounds 12 and 13 were found to exhibit a docking score of -4.10 kcal/mol and -4.38 kcal/mol, respectively. Conclusion: Compounds 12 and 13 showed the highest activity followed by 1 and 5. ADME properties of all compounds were in the acceptable range. The active compounds can be taken for lead optimization and mechanistic interventions for their in vivo study in the future. � 2021 Bentham Science Publishers.
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    Synthesis and In Silico Studies of C-4 Substituted Coumarin Analogues as Anticancer Agents
    (Bentham Science Publishers, 2020-06-29T00:00:00) Dandriyal, Jyoti; Kaur, Kamalpreet; Jaitak, Vikas
    Background: Coumarin is a fused ring system and possesses the enormous capability of targeting various receptors participating in the cancer pathway. Coumarin and its derivatives were found to exhibit very rare toxicity and other side effects. It has been found its immense anticancer potential depends on the nature of the group present and its pattern of substitution on the basic nu-cleus. Objectives: Synthesis of C-4 substituted coumarin derivatives and to study their molecular interactions with ER? for the anticancer activity for Breast Cancer. Methods: C-4 substituted coumarins analogues (1-10) have been synthesized using conventional heating and microwave irradiation. Using Schrodinger software, molecular modeling studies were carried out and ADME properties of the compounds were predicted. Results: All the synthesized compounds have shown better G-Score (-6.87 to-8.43 kcal/mol) as compared to the standard drug tamoxifen (-5.28kcal/mol) and auraptene (-3.89kcal/mol). Molecular docking suggests that all compounds fit in the active site of protein as they have the same hydro-phobic pocket as standard drug tamoxifen, and have an acceptable range of ADME properties. Conclusion: Microwave-assisted synthesis showed better results as compared to conventional heat-ing. In silico studies revealed that all the compounds befit in the active site of the protein. ADME properties showed that all compounds are in allowable limits for human oral absorption. In the fu-ture, there is a possibility of in vitro and in vivo studies of the synthesized compounds. � 2021 Bentham Science Publishers.
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    Identification of novel indole based heterocycles as selective estrogen receptor modulator.
    (Elsevier, 2018) Singla, Ramit; Prakash, Kunal; Gupta Kunj Bihari; Upadhyay, Shishir; Dhiman, Monisha; Jaitak, Vikas
    In the present study, we have designed and synthesized indole derivatives by coalescing the indole nucleus with chromene carbonitrile and dihydropyridine nucleus. Two compounds 5c and 6d were selected from series I and II after sequential combinatorial library generation, docking, absorption, distribution, metabolism and excretion (ADME) filtering, anti-proliferative activity, cytotoxicity, and ER-α competitor assay kit by utilizing estrogen receptor-α (ER-α) dominant T47D BC cells line and PBMCs (Peripheral Blood Mononuclear Cells). Cell imaging experiment suggested that both the compounds successfully cross cellular biomembrane and accumulate in nuclear, cytoplasmic and plasma membrane region. Semiquantitative RT-PCR and Western blotting experiments further supported that both compounds reduced the expression of mRNA and receptor protein of ER-α, thereby preventing downstream transactivation and signaling pathway in T47D cells line. Current findings imply that 5cand 6d represent novel ER-α antagonists and may be used in the development of chemotherapy for the management of BC.
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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.