Cancer stem cells CD133 inhibition and cytotoxicity of certain 3-phenylthiazolo[3,2-a]benzimidazoles: design,direct synthesis,crystal study and in vitro biological evaluation |
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Authors: | Ghada H. Al-Ansary Hazem A. Ghabbour Sara T. A. Al-Rashood Khalid A. Al-Rashood Radwa A. Eladwy |
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Affiliation: | 1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ain Shams University, Abbassia, Cairo, Egypt;2. Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia;3. Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt;4. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Egyptian Russian University, Badr City, Cairo, Egypt |
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Abstract: | Cancer stem cells (CSCs) have been objects of intensive study since their identification in 1994. Adopting a structural rigidification approach, a novel series of 3-phenylthiazolo[3,2-a]benzimidazoles 4a–d was designed and synthesised, in an attempt to develop potent anticancer agent that can target the bulk of tumour cells and CSCs. The anti-proliferative activity of the synthesised compounds was evaluated against two cell lines, namely; colon cancer HT-29 and triple negative breast cancer MDA-MB-468 cell lines. Also, their inhibitory activity against the cell surface expression of CD133 was examined. In particular, compound 4b emerged as a promising hit molecule as it manifested good antineoplastic potency against both tested cell lines (IC50?=?9 and 12?μM, respectively), beside its ability to inhibit the cell surface expression of CD133 by 50% suggesting a promising potential of effectively controlling the tumour by eradicating the tumour bulk and inhibiting the proliferation of the CSCs. Moreover, compounds 4a and 4c showed moderate activity against HT-29 (IC50?=?21 and 29?μM, respectively) and MDA-MB-468 (IC50?=?23 and 24?μM, respectively) cell lines, while they inhibited the CD133 expression by 14% and 48%, respectively. Finally, a single crystal X-ray diffraction was recorded for compound 4d. |
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Keywords: | Cancer stem cells CD133 cytotoxicity colon cancer benzimidazoles X-ray |
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