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Synthesis of novel 1,2,3-triazole hybrids of methyl β-orsellinate with capabilities to arrest cell cycle and induce apoptosis in breast cancer cells (MCF-7)

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Abstract

A total of eleven novel 1,2,3-triazole hybrids were synthesized in excellent yields from methyl β-orsellinate through a two-step protocol with 1,3-dipolar cycloaddition as the key step. The newly synthesized compounds have been evaluated for their anti-proliferative potential against a panel of cancer cell lines viz. DU-145, MCF-7, PC-3, IMR-32, and HEK-293T. Interestingly, one of the compounds exhibited higher cytotoxicity on MCF-7 cells with an IC50 of 5 µM as compared to non-cancerous HEK293T cells (23.28 µM). Flow cytometry analysis and acridine orange/ethidium bromide dual staining have showed the significant G0/G1 phase arrest and effective induction of apoptosis, respectively. Furthermore, the inhibition of CDK4/Cyclin D1 complex proteins and thereby downregulation of p-Rb and E2F1 showed that this compound can act as a potent cell-cycle inhibitor. Docking studies also indicated that the compound may act as a strong ATP competitive inhibitor of CDK4/Cyclin D1 complex. Evidently, the methyl β-orsellinate conjugates of 1,2,3-triazole hybrids could be the effective anticancer leads in breast cancer therapeutics.

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Acknowledgements

The authors acknowledge Y. Suresh for conducting flow cytometry analysis. We acknowledge CSIR-IICT for evaluating the manuscript and providing with communication number IICT/Pubs/2020/331. This work was supported by the Research Fund of DBT, Project Number: SAG-K-120917-0495.

Funding

This article was funded by Council of Scientific and Industrial Research, India, Research Fellowship: STR, VKKM, JJM.

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Authors and Affiliations

  1. Centre for Natural Products and Traditional Knowledge, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500007, India

    Srilakshmi Tirupathamma Reddy & Venkata Mallavadhani Uppuluri

  2. Applied Biology Department, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500007, India

    Maresha Ramakrishna, Venkata Krishna Kanth Makani, Jolly Janette Mendonza, Prajitha Mohandas Edathara & Manika Pal Bhadra

  3. Academy of Scientific and Innovative Research (AcSIR), CSIR-Human Resource Development Centre (CSIR-HRDC) Campus, Uttar Pradesh, Postal Staff College Area, Sector 19, Kamla Nehru Nagar, Ghaziabad, India

    Srilakshmi Tirupathamma Reddy, Maresha Ramakrishna, Venkata Krishna Kanth Makani & Jolly Janette Mendonza

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  1. Srilakshmi Tirupathamma Reddy
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  2. Maresha Ramakrishna
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Correspondence to Manika Pal Bhadra or Venkata Mallavadhani Uppuluri.

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Reddy, S.T., Ramakrishna, M., Makani, V.K.K. et al. Synthesis of novel 1,2,3-triazole hybrids of methyl β-orsellinate with capabilities to arrest cell cycle and induce apoptosis in breast cancer cells (MCF-7). Monatsh Chem 153, 461–473 (2022). https://doi.org/10.1007/s00706-022-02922-y

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  • DOI: https://doi.org/10.1007/s00706-022-02922-y

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