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. 2020 Apr 2;10(23):13507-13516.
doi: 10.1039/d0ra00990c. eCollection 2020 Apr 1.

Synthesis of α-indolylacrylates as potential anticancer agents using a Brønsted acid ionic liquid catalyst and the butyl acetate solvent

Ahmed El-Harairy  1   2 , Mennatallah Shaheen  3 , Jun Li  2 , Yuzhou Wu  2 , Minghao Li  2 , Yanlong Gu  2   4
Affiliations

Synthesis of α-indolylacrylates as potential anticancer agents using a Brønsted acid ionic liquid catalyst and the butyl acetate solvent

Ahmed El-Harairy et al. RSC Adv. .

Abstract

In this study, new α-indolylacrylate derivatives were synthesized by the reaction of 2-substituted indoles with various pyruvates using a Brønsted acid ionic liquid catalyst in butyl acetate solvent. This is the first report on the application of pyruvate compounds for the synthesis of indolylacrylates. The acrylate derivatives could be obtained in good to excellent yields. A preliminary biological evaluation revealed their promising anticancer activity (IC50 = 9.73 μM for the compound 4l) and indicated that both the indole core and the acrylate moieties are promising for the development of novel anticancer drugs. The Lipinski's rule and Veber's parameters were assessed for the newly synthesized derivatives.

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Conflict of interest statement

The authors declare that they have no competing financial interest.

Figures

Fig. 1
Fig. 1. Chemical structure of caffeic acid phenethyl ester (CAPE).
Fig. 2
Fig. 2. The reported indole acrylate-based anticancer agents.
Scheme 1
Scheme 1. Routes for the synthesis of C3-functionalized indoles.
Scheme 2
Scheme 2. Scope of the substrates with respect to the indole component.
Scheme 3
Scheme 3. Scope of the substrates with respect to the ketone component.
Scheme 4
Scheme 4. The proposed reaction mechanism for the synthesis of α-indolylacrylates.
Scheme 5
Scheme 5. Schematic for the synthesis of electro-rich indolylacrylates.
Scheme 6
Scheme 6. The proposed reaction mechanism for the synthesis of the compounds 4r and 4s.
Scheme 7
Scheme 7. The proposed reaction mechanism for the synthesis of compound 5a.
Fig. 3
Fig. 3. MTT assays of cell relative viability. (a) Herein, 100 μM 4a–s and 5a were incubated with the HeLa cells for 48 h. ns represents P > 0.05, * represents p value < 0.05, ** represents p value < 0.01, and **** represents p value < 0.001. The significant difference was compared with the control group.
Fig. 4
Fig. 4. The compound 4l at different concentrations was incubated with the HeLa cells for 48 h. The IC50 is 9.73 μM.
See this image and copyright information in PMC

References

    1. Finefield J. M. Frisvad J. C. Sherman D. H. Williams R. M. J. Nat. Prod. 2012;75:812–833. doi: 10.1021/np200954v. - DOI - PMC - PubMed
    2. Shiri M. Chem. Rev. 2012;112:3508–3549. doi: 10.1021/cr2003954. - DOI - PubMed
    3. Shiri M. Zolfigol M. A. Kruger H. G. Tanbakouchian Z. Chem. Rev. 2010;110:2250–2293. doi: 10.1021/cr900195a. - DOI - PubMed
    4. Humphrey G. R. Kuethe J. T. Chem. Rev. 2006;106:2875. doi: 10.1021/cr0505270. - DOI - PubMed
    5. Bhadury P. S. Pang J. Curr. Org. Chem. 2014;18:2108–2124. doi: 10.2174/1385272819666140809010818. - DOI
    1. Fantacuzzi M. De Filippis B. Gallorini M. Ammazzalorso A. Giampietro L. Maccallini C. Aturki Z. Donati E. Ibrahim R. S. Shawky E. Cataldi A. Amoroso R. Eur. J. Med. Chem. 2020;185:111815. doi: 10.1016/j.ejmech.2019.111815. - DOI - PubMed
    2. Al-Wabli R. I. Almomen A. A. Almutairi M. S. Keeton A. B. Piazza G. A. Attia M. I. Drug Des. Dev. Ther. 2020;14:483–495. doi: 10.2147/DDDT.S227862. - DOI - PMC - PubMed
    3. Demurtas M. Baldisserotto A. Lampronti I. Moi D. Balboni G. Pacifico S. Vertuani S. Manfredini S. Onnis V. Bioorg. Chem. 2019;85:568–576. doi: 10.1016/j.bioorg.2019.02.007. - DOI - PubMed
    4. Cury N. M. Capitão R. M. de Almeida R. do C. B. Artico L. L. Corrêa J. R. Simão dos Santos E. F. Yunes J. A. Correia C. R. D. Eur. J. Med. Chem. 2019;181:111570. doi: 10.1016/j.ejmech.2019.111570. - DOI - PubMed
    5. Li W. Sun H. Xu F. Shuai W. Liu J. Xu S. Yao H. Ma C. Zhu Z. Xu J. Bioorg. Chem. 2019;85:49–59. doi: 10.1016/j.bioorg.2018.12.015. - DOI - PubMed
    6. La Regina G. Bai R. Coluccia A. Naccarato V. Famiglini V. Nalli M. Masci D. Verrico A. Rovella P. Mazzoccoli C. Da Pozzo E. Cavallini C. Martini C. Vultaggio S. Dondio G. Varasi M. Mercurio C. Hamel E. Lavia P. Silvestri R. Eur. J. Med. Chem. 2018;152:283–297. doi: 10.1016/j.ejmech.2018.04.042. - DOI - PubMed
    1. Khan M. F. Anwer T. Bakht A. Verma G. Akhtar W. Alam M. M. Rizvi M. A. Akhter M. Shaquiquzzaman M. Bioorg. Chem. 2019;87:667–678. doi: 10.1016/j.bioorg.2019.03.071. - DOI - PubMed
    2. Vlaicu I. D. Olar R. Maxim C. Chifiriuc M. C. Bleotu C. Stănică N. Vasile Scăeţeanu G. Dulea C. Avram S. Badea M. Appl. Organomet. Chem. 2019;33:1–13. doi: 10.1002/aoc.4976. - DOI
    3. Verma G. Chashoo G. Ali A. Khan M. F. Akhtar W. Ali I. Akhtar M. Alam M. M. Shaquiquzzaman M. Bioorg. Chem. 2018;77:106–124. doi: 10.1016/j.bioorg.2018.01.007. - DOI - PubMed
    4. Fang S. Chen L. Yu M. Cheng B. Lin Y. Morris-Natschke S. L. Lee K. H. Gu Q. Xu J. Org. Biomol. Chem. 2015;13:4714–4726. doi: 10.1039/C5OB00007F. - DOI - PMC - PubMed
    5. Yu-Jen C. Shiao M.-S. Hsu M.-L. Tsai T.-H. Sheng-Yuan W. J. Agric. Food Chem. 2001;49:5615–5619. doi: 10.1021/jf0107252. - DOI - PubMed
    1. Gediya L. K. Njar V. C. Expert Opin. Drug Discovery. 2009;4:1099–1111. doi: 10.1517/17460440903341705. - DOI - PubMed
    2. Junior C. V. Danuello A. Bolzani V. dS. Barreiro E. J. Fraga C. A. M. Curr. Med. Chem. 2007;14:1829–1852. doi: 10.2174/092986707781058805. - DOI - PubMed
    1. Arcadi A. Bianchi G. Chiarini M. D'Anniballe G. Marinelli F. Synlett. 2004;6:944–950. doi: 10.1055/s-2004-822903. - DOI