Download PDF
Synthesis 2023; 55(16): 2526-2536
DOI: 10.1055/a-2053-2811
paper

Green Stereoselective Synthesis and In Silico Anticancer Evaluation of Tetrahydro-β-carboline-Derived Spiro Heterocycles

Maneesh Mohan
a   Department of Chemistry, University of Kerala, Kariavattom, Thiruvananthapuram, 695581, India
,
Susan P. Eldhose
b   Department of Chemistry, St. Michael’s College, Cherthala, Alappuzha, 688539, India
,
Athul Sudheendranath
c   Department of Chemistry, Indian Institute of Technology, Hauz Khas, New Delhi, 110016, India
,
Jayasree E. G.
d   Department of Applied Chemistry, Cochin University of Science and Technology, Kochi, 682022, India
,
Ani Deepthi  ∗
a   Department of Chemistry, University of Kerala, Kariavattom, Thiruvananthapuram, 695581, India
› Author AffiliationsM.N. thanks University of Kerala for the financial support in terms of fellowship.
› Further Information
    Permissions and Reprints All articles of this category


Abstract

A green stereoselective synthesis of spiroheterocycles incorporating a spirooxindole and a 1,2,3,4-tetrahydro-β-carboline (THβC) are demonstrated here by the one-pot, three-component reaction of THβC, isatins, and chalcones. Operational simplicity and chromatography-free isolation are the highlights of the reaction which resulted in densely substituted spiroheterocycles with four-contiguous stereocenters in excellent yields. The activity of the compounds as anticancer agents was studied in silico against MDM2 and PLK1 target proteins and they show excellent binding interactions compared to reference drugs.

Key words

[3+2] cycloaddition - azomethine ylide - 1,2,3,4-tetrahydro-β-carboline - spiroheterocycles

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/a-2053-2811.
  • Supporting Information


Publication History

Received: 19 January 2023

Accepted after revision: 13 March 2023

Accepted Manuscript online:
13 March 2023

Article published online:
18 April 2023

© 2023. Thieme. All rights reserved

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Dehelean CA, Marcovici I, Soica C, Mioc M, Coricovac D, Iurciuc S, Pinzaru I. Molecules 2021; 26: 1109
    CrossrefPubMed
    • 2a Wang J, Gong F, Liang T, Xie Z, Yang Y, Cao C, Chen X. Eur. J. Med. Chem. 2021; 225: 113815
      CrossrefPubMed
    • 2b Ahmad I, Fakhri S, Khan H, Jeandet P, Aschner M, Yu ZL. Chem. Biol. Interact. 2020; 330: 109229 ; and references cited therein
      CrossrefPubMed
    • 3a Cao R, Peng W, Wang Z, Xu A. Curr. Med. Chem. 2007; 14: 479
      CrossrefPubMed
    • 3b Ashok P, Ganguly S, Murugesan S. Mini-Rev. Med. Chem. 2013; 13: 1778
      CrossrefPubMed
    • 3c Ashok P, Lathiya H, Murugesan S. Eur. J. Med. Chem. 2015; 97: 928
      CrossrefPubMed
    • 3d Dai J, Dan W, Schneider U, Wang J. Eur. J. Med. Chem. 2018; 157: 622
      CrossrefPubMed
    • 3e Ferraz CA. A, de Oliveira Junior RG, Picot L, da Silva Almeida JR. G, Nunes XP. Fitoterapia 2019; 137: 104196
      CrossrefPubMed
    • 3f Liu W, Liu X, Liu W, Gao Y, Wu L, Huang Y, Zhao Q. Eur. J. Med. Chem. 2022; 229: 114095
      CrossrefPubMed
    • 4a Zhang M, Sun D. Anti-Cancer Agents Med. Chem. 2015; 15: 537
      CrossrefPubMed
    • 4b Sahoo CR, Paidesetty SK, Padhy RN. Eur. J. Med. Chem. 2019; 162: 752
      CrossrefPubMed
    • 4c Luo B, Song X. Eur. J. Med. Chem. 2021; 224: 113688
      CrossrefPubMed
  • 5 Wang L, Chen X, Yan C. Genes Dis. 2020; 9: 334
    CrossrefPubMed
    • 6a Karpov AS, Rominger F, Müller TJ. Org. Biomol. Chem. 2005; 3: 4382
      CrossrefPubMed
    • 6b Kulkarni A, Abid M, Toeroek B, Huang X. Tetrahedron Lett. 2009; 50: 1791
      Crossref
    • 6c Maity P, Adhikari D, Jana AK. Tetrahedron 2019; 75: 965
      Crossref
    • 6d Avadhani A, Iniyavan P, Acharya A, Gautam V, Chakrabarti S, Ila H. ACS Omega 2019; 4: 17910
      CrossrefPubMed
    • 6e Yin H, Ma Q, Wang Y, Gu X, Feng Z, Wu Y, Wang S. RSC Adv. 2021; 11: 19639
      CrossrefPubMed
    • 6f Byeon HJ, Jung KH, Moon GS, Moon SK, Lee HY. Sci. Rep. 2020; 10: 1
      CrossrefPubMed
    • 7a Meesala R, Mordi MN, Mansor SM. Synlett 2014; 25: 120
      Article in Thieme Connect
    • 7b Kamal A, Sathish M, Prasanthi AV. G, Chetna J, Tangella Y, Srinivasulu V, Alarifi A. RSC Adv. 2015; 5: 90121
      Crossref
  • 8 Ivasiv V, Albertini C, Gonçalves AE, Rossi M, Bolognesi ML. Curr. Top. Med. Chem. 2019; 19: 1694
    CrossrefPubMed
  • 9 Soni JP, Yeole Y, Shankaraiah N. RSC Med. Chem. 2021; 12: 730
    CrossrefPubMed
  • 10 Singh M, Amrutha Krishnan AV, Mandal R, Samanta J, Ravichandiran V, Natarajan R, Hazra A. Mol. Diversity 2020; 24: 627
    CrossrefPubMed
  • 11 Poissonnet G, Théret-Bettiol MH, Dodd RH. J. Org. Chem. 1996; 61: 2273
    CrossrefPubMed
  • 12 Zhang X, Liu M, Zhan D, Kaur M, Jasinski JP, Zhang W. New J. Chem. 2022; 46: 3866
    CrossrefPubMed
    • 13a Vidya S, Priya K, Velayudhan Jayasree D, Deepthi A, Biju PG. Synth. Commun. 2019; 49: 1592
      Crossref
    • 13b Sathi V, Thomas NV, Deepthi A. Org. Biomol. Chem. 2020; 18: 7822
      CrossrefPubMed
    • 13c Thomas NV, Sathi V, Deepth A. J. Heterocycl. Chem. 2022; 59: 1407
      Crossref
  • 14 Thomas NV, Meenakshy CB, Leena SS, Deepthi A. Synthesis 2022; 54: 2885 ; and references cited therein
    Article in Thieme ConnectPubMed
  • 15 Caramori GF, Galembeck SE, Laali KK. J. Org. Chem. 2005; 70: 3242
    CrossrefPubMed
  • 16 Cammi R, Mennucci B, Tomasi J. J. Phys. Chem. A 2000; 104: 5631
    Crossref
    • 17a Bhatia R, Kumar B. Eur. J. Med. Chem. 2022; 247: 115020
      PubMed
    • 17b Tong JB, Luo D, Bian S, Zhang X. J. Mol. Liq. 2021; 335: 116235
      Crossref
    • 18a Gollner A, Rudolph D, Arnhof H, Bauer M, Blake SM, Boehmelt G, McConnell DB. J. Med. Chem. 2016; 59: 10147
      CrossrefPubMed
    • 18b Zhang J, Li Y, Guo L, Cao R, Zhao P, Jiang W, Si S. Cancer Biol. Ther. 2009; 8: 2374
      CrossrefPubMed