Design, synthesis and biological evaluation of novel indole-xanthendione hybrids as selective estrogen receptor modulators

Simple item page
dc.contributor.authorSingla, Ramit
dc.contributor.authorGupt,a Kunj Bihari
dc.contributor.authorUpadhyay, Shishir
dc.contributor.authorDhiman Monisha
dc.contributor.authorJaitak Vikas
dc.date.accessioned2018-08-24T03:50:21Z
dc.date.accessioned2024-08-13T10:34:32Z
dc.date.available2018-08-24T03:50:21Z
dc.date.available2024-08-13T10:34:32Z
dc.date.issued2018
dc.description.abstractGround breaking clinical therapeutic advances in the treatment of breast cancer (BC) is the introduction of selective estrogen receptor modulators (SERMs). We have expeditiously designed and synthesized indole-xanthendione hybrids by coalescing the indole nucleus with xanthendione. All the compounds were first screened for anti-proliferative activity, cytotoxicity and ER-? binding affinity by utilizing ER-? dominant T47D BC cell lines, PBMCs and ER-? competitor assay kit. From this study, two representative compounds 6e and 6f showing most promising activity were advanced for gene expression studies for targeting ER-?. Cell imaging experiment undoubtedly indicate that both the compounds were able to cross cellular bio membrane and accumulate thus instigating cytotoxicity. RT-PCR and Western blotting experiments further strengthened that both compounds altered the expression of mRNA and receptor protein of ER-?, thereby forestalling downstream transactivation and signalling pathway in T47D cells line. Structural investigation from induced fit simulation study suggest that indole moiety of the compounds 6e and 6f helps in the anchoring of the xanthendione moiety in the hydrophobic region of the cavity thus enabling the compound to bind in antagonistic conformation similar to bazedoxifene by extensive hydrogen bonding and Van der Waals forces. All these finding collectively imply that compound 6e and 6f represents a novel potent ER-? antagonist and in the development of SERMs for the management of BC.en_US
dc.identifier.citationSingla,Ramit., Gupta Kunj Bihari., Upadhyay Shishir (2018) Design, synthesis and biological evaluation of novel indole-xanthendione hybrids as selective estrogen receptor modulators. Bioorganic & Medicinal Chemistry, 269(1) , 266-277. https://doi.org/10.1016/j.bmc.2017.11.040en_US
dc.identifier.doi10.1016/j.bmc.2017.11.040
dc.identifier.issn9680896
dc.identifier.urihttp://10.2.3.109/handle/32116/1557
dc.identifier.urlhttps://www.sciencedirect.com/science/article/pii/S0968089617317492?via%3Dihub
dc.language.isoen_USen_US
dc.publisherElsevier Ltden_US
dc.subjectBreast cancer; Estrogen receptor alpha; Indole-xanthendione hybrids; RT-PCR SERM; Western blottingen_US
dc.titleDesign, synthesis and biological evaluation of novel indole-xanthendione hybrids as selective estrogen receptor modulatorsen_US
dc.title.journalBioorganic and Medicinal Chemistry
dc.typeArticleen_US

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
1557.pdf
Size:
1.67 MB
Format:
Adobe Portable Document Format
Download

Collections

Biochemistry And Microbial Sciences - Research Publications