Palladium-Catalyzed Synthesis and Anticancer Activity of Paclitaxel-Dehydroepiandrosterone Hybrids

Overview

Journal ACS Omega

Publisher American Chemical Society

Specialty Chemistry

Date 2020 Mar 24

PMID 32201853

Citations 3

Authors

Sheng-Jie Lou

Xiao-Huan Li

Xian-Li Zhou

Dong-Mei Fang

Feng Gao

Affiliations

Soon will be listed here.

Abstract

According to the activity-structure relationship of the C-13 side chain in paclitaxel or docetaxel, eighteen novel paclitaxel-dehydroepiandrosterone (DHEA) hybrids were designed and synthesized by Pd(II)-catalyzed Suzuki-Miyaura cross-coupling of 17-trifluoromethanesulfonic enolate-DHEA with different aryl boronic acids. The in vitro anticancer activity of the hybrids against a human liver cancer cell line (HepG-2) was evaluated by MTT assay, showing that most of these hybrids possessed moderate antiproliferative activity against the HepG-2 cancer cell line. Among these hybrids, three ones (, , and ) with ortho-substituents in the phenyl group of the D-ring of DHEA analogues exhibited moderate anticancer activity. The optimal compound showed superior anticancer activity against the HepG-2 cell line with an IC value of 26.39 μM.

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References

Howarth J, Kenny P, McDonnell S, OConnor A . The design and synthesis of guanosine compounds with in vitro activity against the colon cancer cell line SW480: non-taxane derived mimics of taxol?. Bioorg Med Chem Lett. 2003; 13(16):2693-7. DOI: 10.1016/s0960-894x(03)00543-2. View

Schiff P, Horwitz S . Taxol stabilizes microtubules in mouse fibroblast cells. Proc Natl Acad Sci U S A. 1980; 77(3):1561-5. PMC: 348536. DOI: 10.1073/pnas.77.3.1561. View

Xiao H, Verdier-Pinard P, Fernandez-Fuentes N, Burd B, Angeletti R, Fiser A . Insights into the mechanism of microtubule stabilization by Taxol. Proc Natl Acad Sci U S A. 2006; 103(27):10166-10173. PMC: 1502429. DOI: 10.1073/pnas.0603704103. View

Potter G, Barrie S, Jarman M, Rowlands M . Novel steroidal inhibitors of human cytochrome P45017 alpha (17 alpha-hydroxylase-C17,20-lyase): potential agents for the treatment of prostatic cancer. J Med Chem. 1995; 38(13):2463-71. DOI: 10.1021/jm00013a022. View

Schmidt B, Krehl S, Kelling A, Schilde U . Synthesis of 8-aryl-substituted coumarins based on ring-closing metathesis and Suzuki-Miyaura coupling: synthesis of a furyl coumarin natural product from Galipea panamensis. J Org Chem. 2012; 77(5):2360-7. DOI: 10.1021/jo2026564. View

Schnabel C, Hiersemann M . Total synthesis of jatrophane diterpenes from Euphorbia characias. Org Lett. 2009; 11(12):2555-8. DOI: 10.1021/ol900819u. View

Chen Y, Coussanes G, Souris C, Aillard P, Kaldre D, Runggatscher K . A Domino 10-Step Total Synthesis of FR252921 and Its Analogues, Complex Macrocyclic Immunosuppressants. J Am Chem Soc. 2019; 141(35):13772-13777. PMC: 6837725. DOI: 10.1021/jacs.9b07185. View

Kingston D . Recent advances in the chemistry of taxol. J Nat Prod. 2000; 63(5):726-34. DOI: 10.1021/np000064n. View

Deng G, Zhou B, Wang J, Chen Z, Gong L, Gong Y . Synthesis and antitumor activity of novel steroidal imidazolium salt derivatives. Eur J Med Chem. 2019; 168:232-252. DOI: 10.1016/j.ejmech.2019.02.025. View

10.

Schiff P, Fant J, Horwitz S . Promotion of microtubule assembly in vitro by taxol. Nature. 1979; 277(5698):665-7. DOI: 10.1038/277665a0. View

11.

Manner S, Oltner V, Oredsson S, Ellervik U, Frejd T . Spiro-bicyclo[2.2.2]octane derivatives as paclitaxel mimetics. Synthesis and toxicity evaluation in breast cancer cell lines. Org Biomol Chem. 2013; 11(41):7134-44. DOI: 10.1039/c3ob41417e. View

12.

Ojima I, Das M . Recent advances in the chemistry and biology of new generation taxoids. J Nat Prod. 2009; 72(3):554-65. PMC: 2727999. DOI: 10.1021/np8006556. View

13.

Ruszkowska J, Chrobak R, Zero P, Maurin J, Szawkalo J, Czarnocki Z . The Suzuki-Miyaura reaction in the chemical transformations of vindoline. Acta Biochim Pol. 2007; 54(4):857-61. View

14.

Chen X, Gao F, Wang Q, Huang X, Wang D . Design, synthesis and biological evaluation of paclitaxel-mimics possessing only the oxetane D-ring and side chain structures. Fitoterapia. 2013; 92:111-5. DOI: 10.1016/j.fitote.2013.10.015. View

15.

Fang W, Liang X . Recent progress in structure activity relationship and mechanistic studies of taxol analogues. Mini Rev Med Chem. 2005; 5(1):1-12. DOI: 10.2174/1389557053402837. View

16.

Ojima I, Wang X, Jing Y, Wang C . Quest for Efficacious Next-Generation Taxoid Anticancer Agents and Their Tumor-Targeted Delivery. J Nat Prod. 2018; 81(3):703-721. PMC: 5869464. DOI: 10.1021/acs.jnatprod.7b01012. View

17.

Sahu P, Gidwani B, Dhongade H . Pharmacological activities of dehydroepiandrosterone: A review. Steroids. 2019; 153:108507. DOI: 10.1016/j.steroids.2019.108507. View

18.

Liu C, Strobl J, Bane S, Schilling J, McCracken M, Chatterjee S . Design, synthesis, and bioactivities of steroid-linked taxol analogues as potential targeted drugs for prostate and breast cancer. J Nat Prod. 2004; 67(2):152-9. DOI: 10.1021/np030296x. View

19.

Armstrong R, Niwetmarin W, Aggarwal V . Synthesis of Functionalized Alkenes by a Transition-Metal-Free Zweifel Coupling. Org Lett. 2017; 19(10):2762-2765. DOI: 10.1021/acs.orglett.7b01124. View

20.

Zefirova O, Nurieva E, Lemcke H, Ivanov A, Shishov D, Weiss D . Design, synthesis, and bioactivity of putative tubulin ligands with adamantane core. Bioorg Med Chem Lett. 2008; 18(18):5091-4. DOI: 10.1016/j.bmcl.2008.07.116. View