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

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

Publication History

Received: 19 January 2023

Accepted after revision: 13 March 2023

Accepted Manuscript online:
13 March 2023

Article published online:
18 April 2023

• References

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