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International journal of molecular sciences
Apr 06, 2023;24 (7):

Design, Synthesis and Biological Evaluation of 6-(Imidazo[1,2-a]pyridin-6-yl)quinazoline Derivatives as Anticancer Agents via PI3Kα Inhibition.

Mei Li, Daoping Wang, Qing Li, Fang Luo, Ting Zhong, Hongshan Wu, Liang Xiong, Meitao Yuan, Mingzhi Su, Yanhua Fan
Author Information
  1. Mei Li: State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, China.
  2. Daoping Wang: State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, China.
  3. Qing Li: State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, China.
  4. Fang Luo: State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, China.
  5. Ting Zhong: State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, China.
  6. Hongshan Wu: State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, China.
  7. Liang Xiong: State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, China.
  8. Meitao Yuan: State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, China.
  9. Mingzhi Su: State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, China.
  10. Yanhua Fan: State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, China.
PMID: 37047827 DOI: 10.3390/ijms24076851

Abstract

Aberrant expression of the phosphatidylinositol 3-kinase (PI3K) signalling pathway is often associated with tumourigenesis, progression and poor prognosis. Hence, PI3K inhibitors have attracted significant interest for the treatment of cancer. In this study, a series of new 6-(imidazo[1,2-a]pyridin-6-yl)quinazoline derivatives were designed, synthesized and characterized by H NMR, C NMR and HRMS spectra analyses. In the in vitro anticancer assay, most of the synthetic compounds showed submicromolar inhibitory activity against various tumour cell lines, among which is the most potent compound with IC values ranging from 0.09 μΜ to 0.43 μΜ against all the tested cell lines. Moreover, induced cell cycle arrest at G2/M phase and cell apoptosis of HCC827 cells by inhibition of PI3Kα with an IC value of 1.94 nM. These results suggested that compound might serve as a lead compound for the development of PI3Kα inhibitor.

Keywords

PI3Kα inhibitor cell apoptosis cell cycle arrest imidazo[1,2-a]pyridine quinazoline

References

  1. Front Bioeng Biotechnol. 2021 Oct 14;9:761846 [PMID: 34722481]
  2. Bioorg Med Chem. 2021 Sep 15;46:116346 [PMID: 34403956]
  3. Eur J Med Chem. 2020 Dec 15;208:112865 [PMID: 32987316]
  4. Mol Cancer. 2019 Feb 19;18(1):26 [PMID: 30782187]
  5. Front Cell Dev Biol. 2021 Sep 09;9:709204 [PMID: 34568322]
  6. Thorac Cancer. 2022 Apr;13(7):1027-1039 [PMID: 35178875]
  7. Int J Mol Sci. 2018 Dec 07;19(12): [PMID: 30544563]
  8. Front Oncol. 2015 Jun 16;5:135 [PMID: 26137449]
  9. Bioorg Chem. 2023 Mar;132:106352 [PMID: 36682147]
  10. Acta Pharm Sin B. 2022 Jan;12(1):18-32 [PMID: 35127370]
  11. Bioorg Med Chem. 2018 May 1;26(8):1675-1685 [PMID: 29475582]
  12. Nat Rev Drug Discov. 2021 Oct;20(10):798 [PMID: 34471263]
  13. J Cell Physiol. 2015 Jan;230(1):16-26 [PMID: 24912145]
  14. Nat Rev Cancer. 2015 Jan;15(1):7-24 [PMID: 25533673]
  15. Chem Sci. 2020 May 19;11(23):5855-5865 [PMID: 32953006]
  16. Sci Rep. 2022 Apr 5;12(1):5654 [PMID: 35383226]
  17. Bioorg Chem. 2022 Aug;125:105882 [PMID: 35660838]
  18. Expert Opin Drug Discov. 2021 Aug;16(8):841-850 [PMID: 33823728]
  19. Nature. 2020 Apr;580(7801):136-141 [PMID: 32238925]
  20. RSC Adv. 2020 Aug 28;10(53):32103-32112 [PMID: 35518146]
  21. Int J Mol Sci. 2022 May 20;23(10): [PMID: 35628511]
  22. Eur J Med Chem. 2016 Oct 21;122:731-743 [PMID: 27479483]
  23. Eur J Med Chem. 2019 May 15;170:55-72 [PMID: 30878832]
  24. Oncotarget. 2015 Jan 20;6(2):1315-26 [PMID: 25473901]
  25. Semin Cancer Biol. 2022 Oct;85:69-94 [PMID: 34175443]
  26. Int J Med Chem. 2014;2014:395637 [PMID: 25692041]
  27. Eur J Med Chem. 2018 Feb 25;146:460-470 [PMID: 29407971]
  28. Bioorg Chem. 2021 Jul;112:104848 [PMID: 33819737]
  29. Cancer Manag Res. 2021 May 05;13:3639-3650 [PMID: 33981163]
  30. Cancer Metastasis Rev. 2009 Dec;28(3-4):305-16 [PMID: 20013032]
  31. Virchows Arch. 2016 Jul;469(1):35-43 [PMID: 27059323]
  32. Annu Rev Med. 2016;67:11-28 [PMID: 26473415]
  33. J Immunol Res. 2022 Oct 8;2022:5211368 [PMID: 36254198]
  34. Expert Opin Ther Pat. 2018 Apr;28(4):281-297 [PMID: 29368977]
  35. Sci Rep. 2016 Apr 21;6:24772 [PMID: 27098119]
  36. Nat Biotechnol. 2016 Mar;34(3):295-6 [PMID: 26963553]
  37. Oxid Med Cell Longev. 2022 Mar 22;2022:3710449 [PMID: 35360199]
  38. Cell Cycle. 2022 Aug;21(16):1697-1709 [PMID: 35485293]
  39. Oncol Rep. 2022 Jan;47(1): [PMID: 34751411]
  40. Curr Opin Cell Biol. 2017 Apr;45:62-71 [PMID: 28343126]
  41. IUBMB Life. 2023 Feb;75(2):97-116 [PMID: 36309967]
  42. Front Aging Neurosci. 2022 Jun 02;14:869558 [PMID: 35721026]
  43. Semin Cancer Biol. 2022 May;80:1-17 [PMID: 31866476]
  44. Molecules. 2022 Mar 31;27(7): [PMID: 35408693]
  45. Methods Mol Biol. 2017;1612:1-11 [PMID: 28634931]
  46. Asian Pac J Cancer Prev. 2022 Sep 01;23(9):2943-2951 [PMID: 36172656]
  47. J Med Chem. 2022 Feb 10;65(3):2059-2077 [PMID: 35041425]
  48. Oncologist. 2011;16(4):404-14 [PMID: 21406469]
  49. Wien Klin Wochenschr. 2021 Jan;133(1-2):26-31 [PMID: 32876741]
  50. Cancer Med. 2023 Mar;12(5):5908-5925 [PMID: 36412203]
  51. Chin Med J (Engl). 2022 Jun 5;135(11):1272-1284 [PMID: 35830272]
  52. Mol Cancer Res. 2019 Sep;17(9):1931-1944 [PMID: 31160383]

Grants

  1. 202001/Merit-based Funding Program for Innovation and Entrepreneurship of High-level Overseas Talents of Guizhou Province
  2. QKH-zk [2022]030/Natural Science Foundation of Guizhou Provincial Science and Technology Projects
  3. QKHPTRC[2018]5779-58/Science and Technology Plan Project of Guizhou Province, China
  4. 21907020/National Natural Science Foundation of China
  5. 22167010/National Natural Science Foundation of China

MeSH Term

Quinazolines
Molecular Structure
Structure-Activity Relationship
Phosphatidylinositol 3-Kinases
Drug Screening Assays, Antitumor
Cell Proliferation
Antineoplastic Agents
Cell Line, Tumor
Drug Design

Chemicals

Quinazolines
Phosphatidylinositol 3-Kinases
Antineoplastic Agents
Journal Article

Word Cloud

Created with Highcharts 10.0.0cellPI3KαquinazolinecompoundPI3K6-imidazo[12-a]pyridin-6-ylNMRlinesIC0μΜcyclearrestapoptosisinhibitorAberrantexpressionphosphatidylinositol3-kinasesignallingpathwayoftenassociatedtumourigenesisprogressionpoorprognosisHenceinhibitorsattractedsignificantinteresttreatmentcancerstudyseriesnewderivativesdesignedsynthesizedcharacterizedHCHRMSspectraanalysesvitroanticancerassaysyntheticcompoundsshowedsubmicromolarinhibitoryactivityvarioustumouramongpotentvaluesranging0943testedMoreoverinducedG2/MphaseHCC827cellsinhibitionvalue194nMresultssuggestedmightserveleaddevelopmentDesignSynthesisBiologicalEvaluationImidazo[1DerivativesAnticancerAgentsviaInhibition2-a]pyridine

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