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Synthesis, biological properties and structural study of new halogenated azolo[4,5-b]pyridines as inhibitors of CK2 kinase.

Chojnacki K, Lindenblatt D, Wińska P, Wielechowska M, Toelzer C, Niefind K, Bretner M
Bioorg Chem 106 104502 (2021)
Related entries: 5owh, 5owl, 6hbn, 6hmb, 6hmc, 6hmd, 6hme, 6hmq, 6te2, 6tei, 6tew, 6tgu, 7a1b, 7a1z, 7a22, 7a49, 7a4b, 7a4c

Cited: 2 times
EuropePMC logo PMID: 33317841

Abstract

The new halogenated 1H-triazolo[4,5-b]pyridines and 1H-imidazo[4,5-b]pyridines were synthesised as analogues of known CK2 inhibitors: 4,5,6,7-tetrabromo-1H-benzotriazole (TBBt) and 4,5,6,7-tetrabromo-1H-benzimidazole (TBBi). Their influence on the activity of recombinant human CK2α, CK2α' and PIM1 kinases was determined. The most active inhibitors were di- and trihalogenated 1H-triazolo[4,5-b]pyridines (4a, 5a and 10a) with IC50 values 2.56, 3.82 and 3.26 μM respectively for CK2α. Furthermore, effect on viability of cancer cell lines MCF-7 (human breast adenocarcinoma) and CCRF-CEM (T lymphoblast leukemia) of all final compounds was evaluated. Finally, three crystal structures of complexes of CK2α1-335 with inhibitors 4a, 5a and 10a were obtained. In addition, new protocol was used to obtain high-resolution crystal structures of CK2α'Cys336Ser in complex with four inhibitors (4a, 5a, 5b, 10a).

Articles citing this publication (2)

  1. Exploring the potential of approved drugs for triple-negative breast cancer treatment by targeting casein kinase 2: Insights from computational studies. Shoaib TH, Ibraheem W, Abdelrahman M, Osman W, Sherif AE, Ashour A, Ibrahim SRM, Ghazawi KF, Miski SF, Almadani SA, ALsiyud DF, Mohamed GA, Alzain AA. PLoS One 18 e0289887 (2023)
  2. Synthesis of Novel Acyl Derivatives of 3-(4,5,6,7-Tetrabromo-1H-benzimidazol-1-yl)propan-1-ols-Intracellular TBBi-Based CK2 Inhibitors with Proapoptotic Properties. Chojnacki K, Wińska P, Karatsai O, Koronkiewicz M, Milner-Krawczyk M, Wielechowska M, Rędowicz MJ, Bretner M, Borowiecki P. Int J Mol Sci 22 6261 (2021)


Related citations provided by authors (3)

  1. Biological properties and structural study of new aminoalkyl derivatives of benzimidazole and benzotriazole, dual inhibitors of CK2 and PIM1 kinases.. Chojnacki K, Wińska P, Wielechowska M, Łukowska-Chojnacka E, Tölzer C, Niefind K, Bretner M Bioorg Chem 80 266-275 (2018)
  2. Diacritic Binding of an Indenoindole Inhibitor by CK2α Paralogs Explored by a Reliable Path to Atomic Resolution CK2α' Structures.. Lindenblatt D, Nickelsen A, Applegate VM, Hochscherf J, Witulski B, Bouaziz Z, Marminon C, Bretner M, Le Borgne M, Jose J, Niefind K ACS Omega 4 5471-5478 (2019)
  3. Structural and Mechanistic Basis of the Inhibitory Potency of Selected 2-Aminothiazole Compounds on Protein Kinase CK2.. Lindenblatt D, Nickelsen A, Applegate VM, Jose J, Niefind K J Med Chem 63 7766-7772 (2020)

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