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Bioassay-guided fractionations of Cannabis sativa extract and HPLC-assisted purifications of anti-proliferative active fractions lead to the isolation of 16 known and one new phytomolecule and their in-silico analysis

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A Correction to this article was published on 22 May 2024

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Abstract

The comprehensive anti-cancer activities of cannabinoid acids and non-cannabinoids are not fully explored. Herein we report simple extraction, faster bioassay-guided fractionation, and HPLC-assisted purification of bioactive secondary metabolite and their identification. Anti-proliferative activity of six cannabinoid acids and eleven non-cannabinoids from the leaves of Cannabis sativa was evaluated. HPLC- assisted purification from the bioactive fractions leads to isolate one new compound Methoxy Canniprene (methoxy isoprenyl bibenzyl), including all six CBDA’s eleven non-cannabinoids in a single step, and NMR, HR-ESI-MS studies, and comparison with the literature data authenticated their structures. The crude extract (IC50 range: 18.0–37.2 μg/mL), Fraction A to D (11.9–222 μg/mL), and purified different cannabinoid and non cannabinoids (IC50 range: 0.5–100 μM) displayed potent anti-proliferative activities against almost all the tested five human cancer cell lines. Computational analysis based on molecular docking studies and absolute binding free energy calculation have identified targets for various cancer-associated proteins, including Aldehyde dehydrogenase 1 A1, Topoisomerase I, GSK-3 Beta, Protein Kinase C beta II, and Neurotrophic Tyrosine Kinase receptor type 1.

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Acknowledgements

Yedukondalu Nalli acknowledges fellowship (Aroma Mission project phase-II) from Council of Scientific and Industrial Research (CSIR). Authors are thankful to Director, CSIR-IIIM, Jammu for providing necessary facility and support during the study.

Author contributions

MKV conceived the study. YKN, RS, and JPB performed the extraction and isolation of compounds by using column chromatography and preparative HPLC. SB and TA performed the biological experiments. MKV and YKN carried out structure elucidation of the isolated compounds and MKV drafted the manuscript. AG supervises the work of biological activity and compiled the data. SSB and YPB carried out in silico study and interpretation of the data.

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Authors and Affiliations

  1. Natural Products and Medicinal Chemistry Division, CSIR–Indian Institute of Integrative Medicine, Canal Road, Jammu Tawi, 180 001, J & K, India

    Yedukondalu Nalli, Rohit Singh, Jayaprakash Behera, Yogesh P. Bharitkar & Mahendra Kumar Verma

  2. Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, 201 002, India

    Yedukondalu Nalli, Sahil Bharti, Tanzeeba Amin, Jayaprakash Behera, Yogesh P. Bharitkar, Anindya Goswami & Mahendra Kumar Verma

  3. Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu Tawi, 180001, J & K, India

    Sahil Bharti, Tanzeeba Amin & Anindya Goswami

  4. Department of Bioinformatics, Rajiv Gandhi Institute of Information Technology & Biotechnology, Bharati Vidyapeeth, Pune, Maharashtra, 411 046, India

    Sagar S. Bhayye

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  1. Yedukondalu Nalli
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Correspondence to Anindya Goswami or Mahendra Kumar Verma.

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Nalli, Y., Bharti, S., Amin, T. et al. Bioassay-guided fractionations of Cannabis sativa extract and HPLC-assisted purifications of anti-proliferative active fractions lead to the isolation of 16 known and one new phytomolecule and their in-silico analysis. Med Chem Res 33, 635–650 (2024). https://doi.org/10.1007/s00044-024-03199-y

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