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Cytotoxic and apoptosis-inducing effects of novel 8-amido isocoumarin derivatives against breast cancer cells

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Abstract

Isocoumarin is a lactone, a type of natural organic compound that is used as synthetic intermediates of several natural products and pharmaceutical compounds explored for their potential therapeutic applications like antifungal, antimicrobial, anti-inflammatory, and anticancer activities. In our previous work, we were the first group to report the use of amide C-N bond of isatins as the oxidizing directing group for the synthesis of 8-amido isocoumarin derivatives. Whereas in our present work, we have screened the cytotoxic effects of novel 8-amido isocoumarin derivatives (S1–S10) in human breast cancer MCF-7 and MDA-MB-231 cells. Our novel results revealed that N-(3-(4-methoxyphenyl)-1-oxo-4-(4-propylphenyl)-1H-isochromen-8yl)acetamide (S1) and N-(4-(3,5-difluorophenyl)-1-oxo-3-(p-tolyl)-1H-isochromen-8-yl) acetamide (S2) are the two potent compounds among the rest synthesized isocoumarin derivatives that are cytotoxic against MCF-7 and MDA-MB-231 cells, whereas less toxic to the non-tumorigenic IOSE-364 cells. Flow cytometry studies have confirmed the induction of apoptotic effects of compounds by Annexin V/PI double staining. We also observed the cytotoxic effects of S1 and S2, as evaluated by DAPI-PI immunostaining and H&E staining. The morphological alterations consistent with apoptotic blebs were observed in both cancer cells treated with compounds assessed by scanning electron microscopy. Overall, this present study strongly demonstrates that 8-amido isocoumarin derivatives have potent cytotoxic and apoptotic effects in breast cancer cells.

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Acknowledgements

We are grateful to the Director, CSIR-NEIST, for his keen interests.

Funding

This work is financially supported by SERB-DST, Govt. of India funded Ramanujan Fellowship Award.

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Authors and Affiliations

  1. Biotechnology Group, Biological Sciences and Technology Division, CSIR-North East Institute of Science & Technology, Jorhat, Assam, 785006, India

    Vishal Das, Channakeshavaiah Chikkaputtaiah, Hari Prasanna Deka Boruah & Mintu Pal

  2. Academy of Scientific and Innovative Research, Headquarters, CSIR-HRDC Campus , Sector 19, Kamla Nehru Nagar ,Ghaziabaad-201002, India

    Vishal Das, Gauri Duarah, Channakeshavaiah Chikkaputtaiah, Hari Prasanna Deka Boruah & Mintu Pal

  3. Applied Organic Chemistry Group, Chemical Sciences and Technology Division, CSIR-North East Institute of Science & Technology, Jorhat, Assam, 785006, India

    Partha Pratim Kaishap & Gauri Duarah

  4. Department of Pharmaceutical Science, Assam University, Silchar, Assam, 788011, India

    Partha Pratim Kaishap

  5. Government Model College, Kaziranga, Golaghat, Assam, 785609, India

    Hari Prasanna Deka Boruah

  6. Guest Faculty, National Institute of Technology (NIT), Yupia, Papum Pare, Arunachal Pradesh, 791112, India

    Mintu Pal

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  1. Vishal Das
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Contributions

VD designed and executed cytotoxic and apoptotic experiments; PPK and GD synthesized compounds. VD, CC, HPDB, and MP designed, analyzed, and interpreted the data, and co-wrote the manuscript, which was edited and read by all authors. The authors declare that all data were generated in-house and that no paper mill was used.

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Correspondence to Mintu Pal.

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Das, V., Kaishap, P.P., Duarah, G. et al. Cytotoxic and apoptosis-inducing effects of novel 8-amido isocoumarin derivatives against breast cancer cells. Naunyn-Schmiedeberg's Arch Pharmacol 394, 1437–1449 (2021). https://doi.org/10.1007/s00210-021-02063-9

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