Journals / Turkish Journal of Chemistry / 2018 / Cilt: 42 - Sayı: 3

Synthesis of novel SN38-aspirin pro drugs for the treatment of hepato cellular carcinoma

Pages
929–939
Publication Date
2022-11-01
DOI
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AI Summary & Key Takeaways

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⚡ TL;DR(Too Long; Didn't Read)

These findingssuggest that compound 4b may be used as a promising anticancer agent against HCC.

📌 3 Key Takeaways

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Objective & Hypothesis:Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and is a leading cause ofcancer-related death worldwide.
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Key Findings & Data:In this study, 7-ethyl-10-hydroxycamptothecin (SN38), the bioactive metabolite of the anticancer drug irinotecan (CPT-11), which is 100–1000times more potent than CPT-11, was coupled with aspirin to give 4 prodrugs.
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Conclusion & Impact:These findingssuggest that compound 4b may be used as a promising anticancer agent against HCC.
🔬Design:Research Article
📍Scope:Comprehensive Sample
⚙️Variables:Domain Parameters

Abstract

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and is a leading cause ofcancer-related death worldwide. However, there is no effective chemotherapeutic treatment for HCC and its prognosisremains poor. Consequently, it is urgent to find an efficient antitumor agent to treat HCC. In this study, 7-ethyl-10-hydroxycamptothecin (SN38), the bioactive metabolite of the anticancer drug irinotecan (CPT-11), which is 100–1000times more potent than CPT-11, was coupled with aspirin to give 4 prodrugs. Their structures were characterized by1 H NMR and elemental analysis. The in vitro anticancer activities of these compounds on two human hepatocellularcarcinoma cell lines (BEL-7404 and HepG2) and preliminary mechanisms of action were explored. Our data indicatedthat these compounds decreased the viability of cancer cell lines in a concentration- and time-dependent manner. Amongthem, compound 4b significantly inhibited cell viability of HepG2 cells (IC 50 = 0.1208 µ M) when compared with CPT-11 (IC 50 = 18.4267 µ M). Furthermore, compound 4b blocked HepG2 cell migration and invasion in vitro. These findingssuggest that compound 4b may be used as a promising anticancer agent against HCC.

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Cite This Article

CHEN, Z., LUO, Y., FANG, A., FAN, C., ZENG, C. (2022). Synthesis of novel SN38-aspirin pro drugs for the treatment of hepato cellular carcinoma. Turkish Journal of Chemistry, Cilt: 42 - Sayı: 3, 929–939. https://ajindex.com/articles/601794

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References (17)

  1. Ferlay, J.; Soerjomataram, I.; Dikshit, R.; Eser, S.; Mathers, C.; Rebelo, M.; Parkin, D. M.; Forman, D.; Bray, F. Int. J. Cancer 2015, 136, E359-386
  2. Siegel, R. L.; Miller, K. D.; Jemal, A. CA Cancer J. Clin. 2016, 66, 7-30
  3. Giannini, E. G.; Farinati, F.; Ciccarese, F.; Pecorelli, A.; Rapaccini, G. L.; Di Marco, M.; Benvegn`u, L.; Caturelli, E.; Zoli, M.; Borzio, F. et al. Hepatology 2015, 61, 184-190
  4. Stintzing, S.; Modest, D. P.; Rossius, L.; Lerch, M. M.; von Weikersthal, L. F.; Decker, T.; Kiani, A.; Vehling-Kaiser, U.; Al-Batran, S. E.; Heintges, T. et al. Lancet Oncol. 2016, 17, 1426-1434
  5. Noda, K.; Nishiwaki, Y.; Kawahara, M.; Negoro, S.; Sugiura, T.; Yokoyama, A.; Fukuoka, M.; Mori, K.; Watanabe, K.; Tamura, T. et al. N. Engl. J. Med. 2002, 346, 85-91
  6. Boku, N.; Yamamoto, S.; Fukuda, H.; Shirao, K.; Doi, T.; Sawaki, A.; Koizumi, W.; Saito, H.; Yamaguchi, K.; Takiuchi, H. et al. Lancet Oncol. 2009, 10, 1063-1069
  7. Sugiyama, T.; Okamoto, A.; Enomoto, T.; Hamano, T.; Aotani, E.; Terao, Y.; Suzuki, N.; Mikami, M.; Yaegashi, N.; Kato, K. et al. J. Clin. Oncol. 2016, 34, 2881-3887
  8. Jansen, W. J.; Zwart, B.; Hulscher, S. T.; Giaccone, G.; Pinedo, H. M.; Boven, E. Int. J. Cancer 1997, 70, 335-340
  9. Matsuoka, H.; Yano, K.; Seo, Y.; Saito, T.; Tomoda, H.; Takiguchi, S.; Kono, A. Anticancer Drugs 1995, 6, 413-418
  10. Takahata, T.; Ookawa. K.; Suto, K.; Tanaka, M.; Yano, H.; Nakashima, O.; Kojiro, M.; Tamura, Y.; Tateishi, T. Sakata, Y. et al. Basic Clin. Pharmacol. Toxicol. 2008, 102, 399-407
  11. Mathijssen, R. H.; van Alphen, R. J.; Verweij, J.; Loos, W. J.; Nooter, K.; Stoter, G.; Sparreboom, A. Clin. Cancer Res. 2001, 7, 2182-2194
  12. O’Reilly, E. M.; Stuart, K. E.; Sanz-Altamira, P. M.; Schwartz, G. K.; Steger, C. M.; Raeburn, L.; Kemeny, N. E.; Kelsen, D. P.; Saltz, L. B. Cancer 2011, 91, 101-105
  13. Boige, V.; Ta¨ıeb, J.; Hebbar, M.; Malka, D.; Debaere, T.; Hannoun, L.; Magherini, E.; Mignard, D.; Poynard, T.; Ducreux, M. Eur. J. Cancer 2006, 42, 456-459
  14. Sadzuka, Y.; Takabe, H.; Sonobe, T. J. Control. Release 2005, 108, 453-459
  15. Yao, Y.; Su, X.; Xie, Y.; Wang, Y.; Kang, T.; Gou, L.; Yi, C.; Yang, J. Anticancer Drugs 2013, 24, 270-277
  16. Tahara, M.; Inoue, T.; Sato, F.; Miyakura, Y.; Horie, H.; Yasuda, Y.; Fujii, H.; Kotake, K.; Sugano, K. Mol. Cancer Ther. 2014, 13, 1170-1180
  17. Yao, Y.; Yu, L.; Su, X.; Wang, Y.; Li, W.; Wu, Y.; Cheng, X.; Zhang, H.; Wei, X.; Chen, H. et al. J. Control. Release 2015, 220, 5-17.