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Design, synthesis and evaluation of aurone and indanone derivatives as novel antitumor agents

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Abstract

An aurone derivative HJ-1, was isolated from Coreopsis tinctoria in our previous work, showed potential anti-hepatocellular carcinoma activity. From it, seventy-five compounds were synthesized via bioisostere and scaffold hopping strategy, and then submitted to the inhibitory activities evaluation against four tumor cells (HELA, HT-29, A549 and HepG2) through MTT assays. These activities have been discussed in SAR. Based on the results, compounds, thirty compounds showed moderate to good antitumour activity. Among them, five compounds (A3: 3.41 ± 1.03 μM, E3: 5.11 ± 0.23 μM, E8: 4.14 ± 1.21 μM, F2: 5.40 ± 1.18 μM, F4: 7.37 ± 0.87 μM) had achieved a comparable efficiency to the positive control DOX (Doxorubicin) against HT-29 cell lines, Compound A3 and F4 were identified as potential leading compounds.

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Abbreviations

DOX:

Doxorubicin (Hydroxydaunorubicin)

References

  1. Kraehenbuehl L, Weng CH, Eghbali S, Wolchok JD, Merghoub T. Enhancing immunotherapy in cancer by targeting emerging immunomodulatory pathways. Nat Rev Clin Oncol. 2022;19:37–50. https://doi.org/10.1038/s41571-021-00552-7

    Article  CAS  PubMed  Google Scholar 

  2. Bailly C, Thuru X, Quesnel B. Combined cytotoxic chemotherapy and immunotherapy of cancer: modern times. NAR Cancer. 2020;2:20 https://doi.org/10.1093/narcan/zcaa002

    Article  Google Scholar 

  3. Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA-Cancer J Clin. 2023;73:17–48. https://doi.org/10.3322/caac.21763

    Article  PubMed  Google Scholar 

  4. Singh S, Sharma B, Kanwar SS, Kumar A. Lead phytochemicals for anticancer drug development. Front Plant Sci. 2016;7:13 https://doi.org/10.3389/fpls.2016.01667

    Article  Google Scholar 

  5. Dhiman A, Sharma R, Singh RK. Target-based anticancer indole derivatives and insight into structure-activity relationship: a mechanistic review update (2018-2021). Acta Pharmaceutica Sinica B. 2022;12:3006–3027. https://doi.org/10.1016/j.apsb.2022.03.021

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Ai TT, Zhang JN, Wang XD, Zheng XW, Qin XY, Zhang Q, et al. DNA methylation profile is associated with the osteogenic potential of three distinct human odontogenic stem cells. Signal Transduct Target Ther. 2018;3:8 https://doi.org/10.1038/s41392-017-0001-6

    Article  CAS  Google Scholar 

  7. Alfarouk KO, Stock CM, Taylor S, Walsh M, Muddathir AK, Verduzco D, et al. Resistance to cancer chemotherapy: failure in drug response from ADME to P-gp. Cancer Cell Int. 2015;15:13 https://doi.org/10.1186/s12935-015-0221-1

    Article  CAS  Google Scholar 

  8. Tan P, Chen XT, Zhang H, Wei Q, Luo K. Artificial intelligence aids in development of nanomedicines for cancer management. Seminars in Cancer Biology. 2023;89:61–75. https://doi.org/10.1016/j.semcancer.2023.01.005

    Article  CAS  PubMed  Google Scholar 

  9. Toth S, Szepesi A, Tran-Nguyen VK, Sarkadi B, Nemet K, Falson P, et al. Synthesis and anticancer cytotoxicity of azaaurones overcoming multidrug resistance. Molecules. 2020;25:8 https://doi.org/10.3390/molecules25030764

    Article  CAS  Google Scholar 

  10. Marker SC, King AP, Swanda RV, Vaughn B, Boros E, Qian SB, et al. Exploring ovarian cancer cell resistance to rhenium anticancer complexes. Angewandte Chemie-Int Edition. 2020;59:13391–13400. https://doi.org/10.1002/anie.202004883

    Article  CAS  Google Scholar 

  11. Li HB, Fu GH, Zhong WH. Natural quinazolinones: From a treasure house to promising anticancer leads. Eur J Med Chem. 2023;245:20 https://doi.org/10.1016/j.ejmech.2022.114915

    Article  CAS  Google Scholar 

  12. Zhang WL, Li SB, Li CT, Li TY, Huang YY. Remodeling tumor microenvironment with natural products to overcome drug resistance. Front Immunol. 2022;13:22 https://doi.org/10.3389/fimmu.2022.1051998

    Article  CAS  Google Scholar 

  13. Xiao ZY, Morris-Natschke SL, Lee KH. Strategies for the optimization of natural leads to anticancer drugs or drug candidates. Medicinal Research Reviews. 2016;36:32–91. https://doi.org/10.1002/med.21377

    Article  CAS  PubMed  Google Scholar 

  14. Khine MN, Sakurai K. Golgi-targeting anticancer natural products. Cancers. 2023;15:15 https://doi.org/10.3390/cancers15072086

    Article  CAS  Google Scholar 

  15. Asma ST, Acaroz U, Imre K, Morar A, Shah SRA, Hussain SZ, et al. Natural products/bioactive compounds as a source of anticancer drugs. Cancers. 2022;14:23 https://doi.org/10.3390/cancers14246203

    Article  CAS  Google Scholar 

  16. Mohamadkhani A. Gene cluster analysis of marine bacteria seeking for natural anticancer products. Jundishapur J Nat Pharm Prod. 2021;16:6 https://doi.org/10.5812/jjnpp.104665

    Article  CAS  Google Scholar 

  17. Lazinski LM, Royal G, Robin M, Maresca M, Haudecoeur R. Bioactive aurones, indanones, and other hemiindigoid scaffolds: medicinal chemistry and photopharmacology perspectives. J Med Chem. 2022;65:12594–12625. https://doi.org/10.1021/acs.jmedchem.2c01150

    Article  CAS  PubMed  Google Scholar 

  18. Boucherle B, Peuchmaur M, Boumendjel A, Haudecoeur R. Occurrences, biosynthesis and properties of aurones as high-end evolutionary products. Phytochemistry. 2017;142:92–111. https://doi.org/10.1016/j.phytochem.2017.06.017

    Article  CAS  PubMed  Google Scholar 

  19. Alsayari A, Bin Muhsinah A, Hassan MZ, Ahsan MJ, Alshehri JA, Begum N. Aurone: a biologically attractive scaffold as anticancer agent. Eur J Med Chem. 2019;166:417–431. https://doi.org/10.1016/j.ejmech.2019.01.078

    Article  CAS  PubMed  Google Scholar 

  20. Xie F, Zhu HR, Zhang HX, Lang QY, Tang LS, Huang Q, et al. In vitro and in vivo characterization of a benzofuran derivative, a potential anticancer agent, as a novel Aurora B kinase inhibitor. Eur J Med Chem. 2015;89:310–319. https://doi.org/10.1016/j.ejmech.2014.10.044

    Article  CAS  PubMed  Google Scholar 

  21. Sui GQ, Li T, Zhang BY, Wang RZ, Hao HD, Zhou WM. Recent advances on synthesis and biological activities of aurones. Bioorg Med Chem. 2021;29:22 https://doi.org/10.1016/j.bmc.2020.115895

    Article  CAS  Google Scholar 

  22. Park H, Jeon J, Kim K, Choi S, Hong S. Structure-based virtual screening and de novo design of PIM1 inhibitors with anticancer activity from natural products. Pharmaceuticals. 2021;14:18 https://doi.org/10.3390/ph14030275

    Article  CAS  Google Scholar 

  23. Hu JH, Yan J, Chen J, Pang YQ, Huang L, Li XS. Synthesis, biological evaluation and mechanism study of a class of benzylideneindanone derivatives as novel anticancer agents. Medchemcomm. 2015;6:1318–1327. https://doi.org/10.1039/c5md00139k

    Article  CAS  Google Scholar 

  24. Reynolds RC, Ananthan S, Faaleolea E, Hobrath JV, Kwong CD, Maddox C, et al. High throughput screening of a library based on kinase inhibitor scaffolds against Mycobacterium tuberculosis H37Rv. Tuberculosis. 2012;92:72–83. https://doi.org/10.1016/j.tube.2011.05.005

    Article  CAS  PubMed  Google Scholar 

  25. Patil SA, Patil R, Patil SA. Recent developments in biological activities of indanones. Eur J Med Chem. 2017;138:182–198. https://doi.org/10.1016/j.ejmech.2017.06.032

    Article  CAS  PubMed  Google Scholar 

  26. Adole VA, More RA, Jagdale BS, Pawar TB, Chobe SS, Shinde RA, et al. Microwave prompted solvent-free synthesis of new series of heterocyclic tagged 7-arylidene indanone hybrids and their computational, antifungal, antioxidant, and cytotoxicity study. Bioorganic Chem. 2021;115:13 https://doi.org/10.1016/j.bioorg.2021.105259

    Article  CAS  Google Scholar 

  27. Park HS, Nelson DE, Taylor ZE, Hayes JB, Cunningham KD, Arivett BA, et al. Suppression of LPS-induced NF-kappa B activity in macrophages by the synthetic aurone, (Z)-2-((5-(hydroxymethyl) furan-2-yl) methylene) benzofuran-3 (2H)-one. Int Immunopharmacol. 2017;43:116–128. https://doi.org/10.1016/j.intimp.2016.12.004

    Article  CAS  PubMed  Google Scholar 

  28. Shrestha A, Oh HJ, Kim MJ, Pun NT, Magar TBT, Bist G, et al. Design, synthesis, and structure-activity relationship study of halogen containing 2-benzylidene-1-indanone derivatives for inhibition of LPS-stimulated ROS production in RAW 264.7 macrophages. Eur J Med Chem. 2017;133:121–138. https://doi.org/10.1016/j.ejmech.2017.03.049

    Article  CAS  PubMed  Google Scholar 

  29. Kadayat TM, Banskota S, Bist G, Gurung P, Magar TBT, Shrestha A, et al. Synthesis and biological evaluation of pyridine-linked indanone derivatives: Potential agents for inflammatory bowel disease. Bioorg Med Chem Lett. 2018;28:2436–2441. https://doi.org/10.1016/j.bmcl.2018.06.012

    Article  CAS  PubMed  Google Scholar 

  30. Sun H, Ding WN, Song XT, Wang D, Chen MZ, Wang KL, et al. Synthesis of 6-hydroxyaurone analogues and evaluation of their alpha-glucosidase inhibitory and glucose consumption-promoting activity: Development of highly active 5,6-disubstituted derivatives. Bioorg Med Chem Lett. 2017;27:3226–3230. https://doi.org/10.1016/j.bmcl.2017.06.040

    Article  CAS  PubMed  Google Scholar 

  31. Chaturvedi RN, Pendem K, Patel VP, Sharma M, Malhotra S. Design, synthesis, molecular docking, and in vitro antidiabetic activity of novel PPAR gamma agonist. Mon Chem. 2018;149:2069–2084. https://doi.org/10.1007/s00706-018-2207-x

    Article  CAS  Google Scholar 

  32. Chen Y, Yang M, Wang ZJ. (Z)-7,4’-Dimethoxy-6-hydroxy-aurone-4-O-beta-glucopyranoside mitigates retinal degeneration in Rd10 mouse model through inhibiting oxidative stress and inflammatory responses. Cutan Ocul Toxicol.2020;39(36):42. https://doi.org/10.1080/15569527.2019.1685535

    Article  CAS  Google Scholar 

  33. Abdurehman D, Guoruoluo Y, Li J, Liu GY, Xin XL, Aisa HA. Chemical constituents of coreopsis tinctoria. Chem Nat Compd. 2022;58:741–745. https://doi.org/10.1007/s10600-022-03782-y

    Article  CAS  Google Scholar 

  34. Shen J, Hu MY, Tan W, Ding JW, Jiang BP, Xu L, et al. Traditional uses, phytochemistry, pharmacology, and toxicology of Coreopsis tinctoria Nutt.: a review. J Ethnopharmacol. 2021;269:16 https://doi.org/10.1016/j.jep.2020.113690

    Article  CAS  Google Scholar 

  35. Wu H, Maimaitijiang A, Tang D, Xie BX, Niu C, Aisa HA. Synthesis and antitumor activity of heterocylic aurone and its analogue indanone derivatives. Heterocycles. 2022;106:94–116. https://doi.org/10.3987/com-22-14764

    Article  CAS  Google Scholar 

  36. Li Y, Wu H, Zhao H, Tang D, Aisa HA, Hou X. Synthesis and anti-hepatocarcinoma effects of peracetyl glycosyl aurone derivatives. Russ J Gen Chem. 2023;93:148–160. https://doi.org/10.1134/s1070363223010206

    Article  CAS  Google Scholar 

  37. Yu M, Lin MD, Han CY, Zhu L, Li CJ, Yao XQ. Ligand-promoted reaction on silver nanoparticles: phosphine-promoted, silver nanoparticle-catalyzed cyclization of 2-(1-hydroxy-3-arylprop-2-ynyl)phenols. Tetrahedron Lett. 2010;51:6722–6725. https://doi.org/10.1016/j.tetlet.2010.10.065

    Article  CAS  Google Scholar 

  38. Saito K, Yoshida M, Doi T. An efficient synthesis of aurone derivatives by the tributylphosphine-catalyzed regioselective cyclization of o-alkynoylphenols. Chem Lett. 2015;44:141–143. https://doi.org/10.1246/cl.140910

    Article  CAS  Google Scholar 

  39. Wang S, Xu L, Lu YT, Liu YF, Han B, Liu T, et al. Discovery of benzofuran-3(2H)-one derivatives as novel DRAK2 inhibitors that protect islet beta-cells from apoptosis. Eur J Med Chem. 2017;130:195–208. https://doi.org/10.1016/j.ejmech.2017.02.048

    Article  CAS  PubMed  Google Scholar 

  40. Caleffi GS, Rosa AS, de Souza LG, Avelar JLS, Nascimento SMR, de Almeida VM, et al. Aurones: a promising scaffold to inhibit SARS-CoV-2 replication. J Nat Prod. 2023;86:1536–1549. https://doi.org/10.1021/acs.jnatprod.3c00249

    Article  CAS  PubMed  Google Scholar 

  41. Xie B, Zhao H, Hu A, Niu C, Aisa HA. Design, synthesis and evaluation of aurone and indanone derivatives as novel antibacterial agents. https://doi.org/10.21203/rs.3.rs-3295826/v1.

  42. Lee CY, Chew EH, Go ML. Functionalized aurones as inducers of NAD(P)H:quinone oxidoreductase 1 that activate AhR/XRE and Nrf2/ARE signaling pathways: Synthesis, evaluation and SAR. Eur J Med Chem. 2010;45:2957–2971. https://doi.org/10.1016/j.ejmech.2010.03.023

    Article  CAS  PubMed  Google Scholar 

  43. Ruzi Z, Nie L, Bozorov K, Zhao J, Aisa HA. Synthesis and anticancer activity of ethyl 5-amino-1-N substituted-imidazole-4-carboxylate building blocks. Arch Pharm. 2021;354:e2000470 https://doi.org/10.1002/ardp.202000470

    Article  CAS  Google Scholar 

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Acknowledgements

This research was supported by West Light Foundation of the Chinese Academy of Sciences (2023-XBQNXZ-009, “Design, synthesis and activity study of anti-vitiligo lead compounds based on specific targets”, Niu Chao); Special Training Program of Natural Science Foundation of Xinjiang Autonomous Region (2022D03018); West Light Foundation of the Chinese Academy of Sciences (grant No. 2021-JCTD-001).

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Authors and Affiliations

  1. State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, CAS Key Laboratory of Chemistry of Plant Resources in Arid Regions, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi, 830011, China

    Baoxing Xie, Gulmira Turdu, Chao Niu & Haji Akber Aisa

  2. University of Chinese Academy of Sciences, 100049, Beijing, China

    Baoxing Xie, Gulmira Turdu, Chao Niu & Haji Akber Aisa

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  1. Baoxing Xie
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Correspondence to Chao Niu or Haji Akber Aisa.

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Xie, B., Turdu, G., Niu, C. et al. Design, synthesis and evaluation of aurone and indanone derivatives as novel antitumor agents. Med Chem Res 33, 201–220 (2024). https://doi.org/10.1007/s00044-023-03168-x

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