Design, synthesis and biological evaluation of new Myo-inositol derivatives as potential RAS inhibitors

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dc.contributor.author Hussain, Javeena
dc.contributor.author Chhabria, Dimple
dc.contributor.author Kirubakaran, Sivapriya
dc.date.accessioned 2020-06-05T13:50:51Z
dc.date.available 2020-06-05T13:50:51Z
dc.date.issued 2020-08
dc.identifier.citation Hussain, Javeena; Chhabria, Dimple and Kirubakaran, Sivapriya, “Design, synthesis and biological evaluation of new Myo-inositol derivatives as potential RAS inhibitors”, Bioorganic & Medicinal Chemistry Letters, DOI: 10.1016/j.bmcl.2020.127290, vol. 30, no. 16, Aug. 2020. en_US
dc.identifier.issn 0960-894X
dc.identifier.issn 1464-3405
dc.identifier.uri http://dx.doi.org/10.1016/j.bmcl.2020.127290
dc.identifier.uri https://repository.iitgn.ac.in/handle/123456789/5444
dc.description.abstract Ras is a small family of GTPases that control numerous cellular functions like cell proliferation, growth, survival, gene expression, and is closely engaged in cancer pathogenesis. The ras-targeted methodology entails a holy grail in oncology. Nevertheless, there are no specific molecules reported targeting the same, although it is a known oncogene for more than three decades. In this study, we have designed and synthesized new phosphate derivatives of Myo-inositol to inhibit the oncogenic KRAS pathway in breast cancer cells, which has been validated by cellular and theoretical studies. The synthesized compound 1b (C2-O-phosphate derivative of Myo-inositol 1,3,5-orthobenzoate) inhibited the downstream signaling pathway of oncogenic KRAS, RAF/MEK/ERK. Furthermore, we also found that this compound induced necrosis/apoptosis and causes cell cycle arrest. This class of molecules may work as a potential inhibitor of breast cancer caused by a mutation in KRAS and its downstream proteins. Though the efficacy of the molecules is in the micromolar scale, they have not been explored previously for RAS inhibition. Impressive preliminary results are presented in this article which could be further explored for its detailed biological studies to get better candidates as RAS inhibitors.
dc.description.statementofresponsibility by Javeena Hussain, Dimple Chhabria and Sivapriya Kirubakaran
dc.language.iso en_US en_US
dc.publisher Elsevier en_US
dc.subject Breast cancer en_US
dc.subject KRAS en_US
dc.subject Myo-inositol en_US
dc.subject Molecular Docking en_US
dc.subject Antiproliferative activity en_US
dc.title Design, synthesis and biological evaluation of new Myo-inositol derivatives as potential RAS inhibitors en_US
dc.type Article en_US
dc.relation.journal Bioorganic & Medicinal Chemistry Letters


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