School Of Basic And Applied Sciences

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Author: search.filters.author.Dhiman, MonishaSubject: search.filters.subject.Breast cancer

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    New pentacyclic triterpene from Potentilla atrosanguinea Lodd. as anticancer agent for breast cancer targeting estrogen receptor-?
    (Taylor and Francis Ltd., 2021-10-04T00:00:00) Kumar, Amit; Gupta, Kunj Bihari; Dhiman, Monisha; Arora, Saroj; Jaitak, Vikas
    One new (compound 3) along with two previously known ursane type triterpenoids (compounds 1 and 2) were purified by chromatographic techniques from ethyl acetate extract of aerial parts of Potentilla atrosanguniea and characterized by HRMS, 1 D and 2 D-NMR. Compounds 1 (ursolic acid), 2 (euscaphic acid) and 3 (3?,20?-dihydroxy 2-oxo-urs-12-en-28-oic acid) were tested for their antiproliferative activity along with standard bazedoxifene. Compounds 1 and 3 were found to be of higher activity (3.71 and 6.05 ?g/mL) as compared to compound 2 and bazedoxifene (IC50: 24.53 and 17.87 ?g/mL). Anti-estrogenic activity of three compounds on breast cancer (BC) were studied in vitro by accessing their antiproliferative activity and binding with estrogen receptor alpha (ER-?). All three compounds have effective binding affinity towards ER-? and decreased cell growth by downregulating the expression of mRNA and its translational protein as tested by semi-qRT-PCR and western blotting. In terms of effectiveness compounds 1 and 3 were found more active due to their antiproliferative, and antiestrogenic activity as compared to standard bazedoxifene. � 2021 Informa UK Limited, trading as Taylor & Francis Group.
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    New pentacyclic triterpene from Potentilla atrosanguinea Lodd. as anticancer agent for breast cancer targeting estrogen receptor-?
    (Taylor and Francis Ltd., 2021-10-04T00:00:00) Kumar, Amit; Gupta, Kunj Bihari; Dhiman, Monisha; Arora, Saroj; Jaitak, Vikas
    One new (compound 3) along with two previously known ursane type triterpenoids (compounds 1 and 2) were purified by chromatographic techniques from ethyl acetate extract of aerial parts of Potentilla atrosanguniea and characterized by HRMS, 1 D and 2 D-NMR. Compounds 1 (ursolic acid), 2 (euscaphic acid) and 3 (3?,20?-dihydroxy 2-oxo-urs-12-en-28-oic acid) were tested for their antiproliferative activity along with standard bazedoxifene. Compounds 1 and 3 were found to be of higher activity (3.71 and 6.05 ?g/mL) as compared to compound 2 and bazedoxifene (IC50: 24.53 and 17.87 ?g/mL). Anti-estrogenic activity of three compounds on breast cancer (BC) were studied in vitro by accessing their antiproliferative activity and binding with estrogen receptor alpha (ER-?). All three compounds have effective binding affinity towards ER-? and decreased cell growth by downregulating the expression of mRNA and its translational protein as tested by semi-qRT-PCR and western blotting. In terms of effectiveness compounds 1 and 3 were found more active due to their antiproliferative, and antiestrogenic activity as compared to standard bazedoxifene. � 2021 Informa UK Limited, trading as Taylor & Francis Group.
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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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    Design, synthesis and biological evaluation of novel indole-benzimidazole hybrids targeting estrogen receptor alpha (ER-?)
    (Elsevier Masson SAS, 2018) Singla R.; Gupta K.B.; Upadhyay S.; Dhiman, Monisha; Jaitak V.
    In the course of efforts to develop novel selective estrogen receptor modulators (SERMs), indole-benzimidazole hybrids were designed and synthesised by fusing the indole nucleus with benzimidazole. All the compounds were first inspected for anti-proliferative activity using ER-? responsive T47D breast cancer cell lines and ER-? binding assay. From this study, two representative bromo substituted compounds 5f and 8f were found to be most active and thus were escalated for gene expression studies for targeting ER-?. Cell imaging experiment clearly suggest that compounds were able to cross cell membrane and accumulate thus causing cytotoxicity. RT-PCR and Western blotting experiments further supported that both compounds altered the expression of mRNA and receptor protein of ER-?, thereby preventing the further transactivation and signalling pathway in T47D cells lines. Structural investigation from induced fit simulation study suggest that compound 5f and 8f bind in antagonistic conformation similar to bazedoxifene by extensive hydrogen bonding and Van der Waals forces. All these results strongly indicate that compound 5f and 8f represents a novel potent ER-? antagonist properties and will proved promising in the discovery of SERM for the management of breast cancer.