Investigating the in vitro Antitumor Structure-activity Relationship of a Range of Cannabinolic Acid Derivatives

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DOI: https://doi.org/10.30564/jor.v5i1.5115

Abstract:

Aim: To investigate the in vitro structure-activity relationship (SAR) of a range of tetrahydrocannabinolic (THCA) and cannabidiolic (CBDA) derivatives using the PANC-1 tumor cell line (pancreas, ductal carcinoma). Materials and methods: The in vitro effects of a range of THCA and CBDA derivatives with different carbonyl group substituents were tested on the PANC-1 cells cell line using the CellTiter Glo Viability Assay (72 hours) and the XTT assay (48 hours). Results: A study of a series of THCA and CBDA derivatives containing different functional groups at the carbonyl nitrogen atom demonstrated that THCA amides have better inhibitory activity, on the PANC-1 tumor cell line, than CBDA derivatives. Conclusions: THCA derivatives have better inhibitory activity than CBDA analogs with the same substituents. It is noteworthy that even a slight change in the structure of the substituent of the amide or hydrazone moiety of the molecule has a dramatic effect on the activity of these compounds.

References:

[1]Daniel, A., Ladin, D.A., Soliman, E., et al., 2016. Preclinical and clinical assessment of cannabinoids as anti-cancer agents. Front Pharmacology. 7, 1-18. DOI: https://doi.org/10.3389/fphar.2016.00361 [2]Śledziński, P., Zeyland, J., Słomski, R., et al., 2017. The current state and future perspectives of cannabinoids in cancer biology. Cancer Medicine. 7, 765- 775. DOI: https://doi.org/10.1002/cam4.1312 [3]Kovalchuk, O., Kovalchuk, I., 2020. Cannabinoids as anticancer therapeutic agents. Cell Cycle. 1-29. DOI: https://doi.org/10.1080/15384101.2020.1742952 [4]Abrams, D.I., Guzmán, M., 2015. Cannabis in Cancer Care. Clinical Pharmacology & Therapeutics. 97, 575-586. DOI: https://doi.org/10.1002/cpt.108 [5]Velasco, G., Sánchez, C., Guzmán, M., 2016. Anticancer mechanisms of cannabinoids. Current Oncology. 23, 23-32. DOI: http://dx.doi.org/10.3747/co.23.3080 [6]Byunghyuck, J., Jungkyu, K.L., Jungdam, K., et al., 2019. Chemistry Asian Journal. 1-15. DOI: https://doi.org/10.1002/asia.201901179 [7]Aizikovich, A., 2021. Cannabinoids and cancer-what’s next? Journal of Biomedical Science. 233- 236. DOI: https://doi.org/10.34297/AJBSR.2021.14.001983 [8]Aizikovich, A. Cannabinolic acid derivatives and used thereof. Patent US 20210087159. [9]Aizikovich, A., 2021. In vitro activity of novel cannabinoids derived from tetrahydrocannabinolic acid on various human tumor cell lines. Journal of Oncology Research. 3(2), 55-59. [10]Aizikovich, A., 2020. Anticancer Effect of New Cannabinoids Derived from Tetrahydrocannabinolic Acid on PANC-1 and AsPC-1 Human Pancreas Tumor Cells. Journal of Pancreatic Cancer. 6(1), 40-44. DOI: https://doi.org/10.1089/pancan.2020.0003 [11] Zhang, J.H., Chung, D.Y., Oldenburg, K.R., 1999. A Simple Statistical Parameter for Use in Evaluation and Validation of High Throughput Screening Assays. Journal of Biomolecular Screening. 4, 67-73. DOI: https://doi.org/10.1177/108705719900400206