TY - JOUR
T1 - Synthesis of novel thiourea-/urea-benzimidazole derivatives as anticancer agents
AU - Siddig, Lamia A.
AU - Khasawneh, Mohammad A.
AU - Samadi, Abdelouahid
AU - Saadeh, Haythem
AU - Abutaha, Nael
AU - Wadaan, Mohammad Ahmed
N1 - Funding Information:
Funding information: The research was funded by Vice Deanship of Scientific Research Chairs, King Saud University.
Funding Information:
The authors are grateful to the Deanship of Scientific Research, King Saud University, for funding through Vice Deanship of Scientific Research Chairs.
Publisher Copyright:
© 2021 Lamia A. Siddig et al., published by De Gruyter.
PY - 2021/1/1
Y1 - 2021/1/1
N2 - A new series of urea and thiourea derivatives containing benzimidazole group as potential anticancer agents have been designed and synthesized. The structures of the synthesized compounds were characterized and confirmed by spectroscopic techniques such as 1H NMR, 13C NMR, and mass spectrometry. In vitro anticancer assay against two breast cancer (BC) cell lines, MDA-MB-231ER(-)/PR(-) and MCF-7ER(+)/PR(+), revealed that the cytotoxicity of 1-(2-(1H-benzo[d]imidazol-2-ylamino)ethyl)-3-p-tolylthiourea (7b) and 4-(1H-benzo[d]imidazol-2-yl)-N-(3-chlorophenyl)piperazine-1-carboxamide (5d) were higher in MCF-7 with IC50 values of 25.8 and 48.3 μM, respectively, as compared with MDA-MB-231 cells. Furthermore, 7b and 5d were assessed for their apoptotic potential using 4′,6-diamidino-2-phenylindole, acridine orange/ethidium bromide staining, and Caspase-3/7. After incubation with MCF-7, the compounds 7b and 5d induced apoptosis through caspase-3/7 activation. In conclusion, the compounds 7b and 5d are potential candidates for inducing apoptosis in different genotypic BC cell lines.
AB - A new series of urea and thiourea derivatives containing benzimidazole group as potential anticancer agents have been designed and synthesized. The structures of the synthesized compounds were characterized and confirmed by spectroscopic techniques such as 1H NMR, 13C NMR, and mass spectrometry. In vitro anticancer assay against two breast cancer (BC) cell lines, MDA-MB-231ER(-)/PR(-) and MCF-7ER(+)/PR(+), revealed that the cytotoxicity of 1-(2-(1H-benzo[d]imidazol-2-ylamino)ethyl)-3-p-tolylthiourea (7b) and 4-(1H-benzo[d]imidazol-2-yl)-N-(3-chlorophenyl)piperazine-1-carboxamide (5d) were higher in MCF-7 with IC50 values of 25.8 and 48.3 μM, respectively, as compared with MDA-MB-231 cells. Furthermore, 7b and 5d were assessed for their apoptotic potential using 4′,6-diamidino-2-phenylindole, acridine orange/ethidium bromide staining, and Caspase-3/7. After incubation with MCF-7, the compounds 7b and 5d induced apoptosis through caspase-3/7 activation. In conclusion, the compounds 7b and 5d are potential candidates for inducing apoptosis in different genotypic BC cell lines.
KW - anticancer activity
KW - apoptosis
KW - benzimidazole
KW - piperazine
KW - thiourea
KW - urea
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U2 - 10.1515/chem-2021-0093
DO - 10.1515/chem-2021-0093
M3 - Article
AN - SCOPUS:85118502833
SN - 2391-5420
VL - 19
SP - 1062
EP - 1073
JO - Open Chemistry
JF - Open Chemistry
IS - 1
ER -