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1,2,3-Triazole-Chalcone hybrids: Synthesis, in vitro cytotoxic activity and mechanistic investigation of apoptosis induction in multiple myeloma RPMI-8226

Ashour, Heba F. ; Abou-zeid, Laila A. ; El-Sayed, Magda A. -A. ; Selim, Khalid B.

European journal of medicinal chemistry, 2020-03, Vol.189, p.112062-112062, Article 112062 [Periódico revisado por pares]

France: Elsevier Masson SAS

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  • Título:
    1,2,3-Triazole-Chalcone hybrids: Synthesis, in vitro cytotoxic activity and mechanistic investigation of apoptosis induction in multiple myeloma RPMI-8226
  • Autor: Ashour, Heba F. ; Abou-zeid, Laila A. ; El-Sayed, Magda A. -A. ; Selim, Khalid B.
  • Assuntos: 1,2,3-Triazole ; Antiproliferative activity ; Apoptosis ; Cell cycle analysis ; Chalcone ; NCI-60 ; ROS
  • É parte de: European journal of medicinal chemistry, 2020-03, Vol.189, p.112062-112062, Article 112062
  • Notas: ObjectType-Article-1
    SourceType-Scholarly Journals-1
    ObjectType-Feature-2
    content type line 23
  • Descrição: A new series of 1,2,3-triazole-chalcone hybrids has been synthesized and screened in vitro against a panel of 60 human cancer cell lines according to NCI (USA) protocol. Compound 4d having 3, 4-dimethoxyphenyl chalcone moiety, the most potent derivative, inhibited the growth of RPMI-8226 and SR leukemia cell lines by 99.73% and 94.95% at 10 μM, respectively. Also, it inhibited the growth of M14 melanoma, K-562 leukemia, and MCF7 breast cancer cell lines by more than 80% at the same test concentration. 4d showed IC50 values less than 1 μM on six types of tumor cells and high selectivity index reached to 104 fold on MCF7. Compound 4d showed superior activity than methotrexate and gefitinib against the most sensitive leukemia cell lines in addition to higher or comparable activity against the rest sensitive cell lines. Flow cytometry analysis in RPMI-8226 cells revealed that compound 4d caused cell cycle arrest at G2/M phase and induced apoptosis in a dose dependant manner. Mechanistic evaluation referred this apoptosis induction to triggering mitochondrial apoptotic pathway through inducing ROS accumulation, increasing Bax/Bcl-2 ratio and activation of caspases 3, 7 and 9. [Display omitted] •New 1,2,3-triazole-chalcone hybrids were synthesized and screened against NCI-60 human cancer cell lines.•Compound 4d (with 3, 4-dimethoxyphenyl) was the most potent anticancer agent.•Compound 4d showed IC50 values less than 1 μM on 6 cancer cell lines with high SI.•Compound 4d induce cell cycle arrest in RPMI-8226 cell line at G2/M phase.•Compound 4d triggered mitochondrial apoptotic pathway.•The action of compound 4d is through accumulation of ROS, up regulation of BAX, down regulation of Bcl-2 and activation of caspases 3, 7, 9.
  • Editor: France: Elsevier Masson SAS
  • Idioma: Inglês
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  • Realização: ABCD-USP USP   Logos de Redes Sociais: Freepik

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