Indolin-2-one derivatives as selective Aurora B kinase inhibitors targeting breast cancer

Dokla, Eman M.E.; Abdel-Aziz, Amal Kamal; Milik, Sandra N.; Mahmoud, Abeer E.; Saadeldin, Mona Kamal; McPhillie, Martin J.; Minucci, Saverio; Abouzid, Khaled A. M.

doi:10.1016/j.bioorg.2021.105451

Cited by 9 publications

(2 citation statements)

References 62 publications

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“…Cell cycle is composed of four distinct phases: G1, S, G2, and M 45 . Flow cytometry analysis of DNA ploidy in MDA-MB-468 breast cancer cells was used to evaluate the influence of compound 12d on normal cell cycle progression 46 . MDA-MB-468 cells, were incubated with 12d for 24h at its IC 50 concentration (3.99 μM) to induce a significant disruption in the cell cycle profile (Fig.…”

Section: Cell Cycle Analysismentioning

confidence: 99%

Synthesis and anticancer activity of new benzensulfonamides incorporating s-triazines as cyclic linkers for inhibition of carbonic anhydrase IX

Zain-Alabdeen

El‐Moselhy

Sharafeldin

et al. 2022

Sci Rep

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Limited presence of hCA IX in normal physiological tissues and their overexpression only in solid hypoxic tumors made this isoform excellent possible target for developing new anticancer agents. We reported designing and synthesis of two novel series of benzenesulfonamides derivatives as hCA IX inhibitors bearing rigid cyclic linkers (1,3,5-dihydrotriazine in series A and 1,3,5-triazine in series B) in replace of traditional linear linkers. Also, novel cyanoethenyl spacer was assembled next to the 1,3,5-triazine linker in series B. Target compounds of series (A) and (B) were screened against four hCA isoforms. Human CA IX efficiently inhibited in series (A) by compound 5a (KI = 134.8 nM). Meanwhile, in series (B) the most active inhibitor was 12i (KI = 38.8 nM). US-NCI protocol was followed to evaluate the anticancer activity of target compounds against panel of sixty cancer cell lines. Compound 12d, exposed the best activity towards breast cancer (MDA-MB-468) with GI% = 62%. The most active analogues, 12d and 12i were further screened for in vitro cytotoxic activity under hypoxic condition against breast cancer (MDA-MB-468) (IC50 = 3.99 ± 0.21 and 1.48 ± 0.08 µM, respectively) and leukemia (CCRF-CM) cell line (IC50 = 4.51 ± 0.24 and 9.83 ± 0.52 µM, respectively). In addition, 12d arrested breast cancer MDA-MB-468 cell cycle in G0-G1 and S phases and induced its apoptosis which indicated by increasing the level of cleaved caspases 3 and 9. Molecular docking was performed for selected analogues to understand their biological alterations. This study revealed that insertion of 1,3,5-triazines as cyclic linkers enhanced the significant anticancer and hCA IX inhibition activity of benzenesulfonamides.

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Section: Cell Cycle Analysismentioning

confidence: 99%

Synthesis and anticancer activity of new benzensulfonamides incorporating s-triazines as cyclic linkers for inhibition of carbonic anhydrase IX

Zain-Alabdeen

El‐Moselhy

Sharafeldin

et al. 2022

Sci Rep

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show abstract

“…Cell cycle analysis was carried out using propidium iodide staining and performed using FACS Celesta as previously described 88,89 . Analysis of cell cycle distribution pattern was performed using FlowJo software.…”

Section: Cell Cycle Analysismentioning

confidence: 99%

Discovery of a benzimidazole-based dual FLT3/TrKA inhibitor targeting acute myeloid leukemia

Dokla

Abdel-Aziz

Milik

et al. 2022

Bioorganic & Medicinal Chemistry

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Discovery of EMD37, a 1,2,4-oxadiazole derivative, as a novel endoplasmic reticulum stress inducer with potent anticancer activity

Abdel-Aziz

Dokla

Abouzid

et al. 2022

Biochemical Pharmacology

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Indolin-2-one derivatives as selective Aurora B kinase inhibitors targeting breast cancer

Cited by 9 publications

References 62 publications

Synthesis and anticancer activity of new benzensulfonamides incorporating s-triazines as cyclic linkers for inhibition of carbonic anhydrase IX

Synthesis and anticancer activity of new benzensulfonamides incorporating s-triazines as cyclic linkers for inhibition of carbonic anhydrase IX

Discovery of a benzimidazole-based dual FLT3/TrKA inhibitor targeting acute myeloid leukemia

Discovery of EMD37, a 1,2,4-oxadiazole derivative, as a novel endoplasmic reticulum stress inducer with potent anticancer activity

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