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. (1st January 2017)

• Record Type: Journal Article
• Authors: Al-Ansary, Ghada H.; Eldehna, Wagdy M.; Ghabbour, Hazem A.; Al-Rashood, Sara T. A.; Al-Rashood, Khalid A.; Eladwy, Radwa A.; Al-Dhfyan, Abdullah; Kabil, Maha M.; Abdel-Aziz, Hatem A.
• Is Part Of: Journal of enzyme inhibition and medicinal chemistry. Volume 32:Number 1(2017)
• Page Start: 986
• Page End: 991
• Publication Date: 2017-01-01
• Subjects: Cancer stem cells -- CD133 -- cytotoxicity -- colon cancer -- benzimidazoles -- X-ray; Enzyme inhibitors -- Periodicals; Enzyme Inhibitors -- periodicals; Biochemistry -- periodicals; 572.7
• DOI: 10.1080/14756366.2017.1347166
• Languages: English
• ISSNs: 1475-6366

Abstract

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 .