Antitumor activity of amidino-substituted benzimidazole and benzimidazo[1,2-a]quinoline derivatives tested in 2D and 3D cell culture systems.
Due to a poor clinical predictive power of 2D cell cultures, standard tool for in vitro assays in drug discovery process, there is increasing interest in developing 3D in vitro cell cultures, biologically relevant assay feasible for the development of robust preclinical anti-cancer drug screening platforms. Herein, we tested amidino-substituted benzimidazoles and benzimidazo[1,2-a]quinolines as a small platform for comparison of antitumor activity in 2D and 3D cell culture systems and correlation with structure-activity relationship. 3D cell culture method was applied on a human cancer breast (SK-BR-3, MDA-MB-231, T-47D) and pancreatic cancer cells (MIA PaCa-2, PANC-1). Results obtained in 2D and 3D models were highly comparable, but in some cases we have observed significant disagreement indicating that some prominent compounds can be discarded in early phase of researching because of compounds with false positive result. To confirm which of cell culture systems is more accurate, in vivo profiling is needed.
a Pharmacology in Vitro , Zagreb , Croatia .
Karmen
K
Brajša
b Chemistry, Fidelta D.O.O. , Zagreb , Croatia , and.
Ines
I
Vujasinović
a Pharmacology in Vitro , Zagreb , Croatia .
Dubravko
D
Jelić
a Pharmacology in Vitro , Zagreb , Croatia .
Marija
M
Trzun
a Pharmacology in Vitro , Zagreb , Croatia .
Ivo
I
Zlatar
c Department of Organic Chemistry , Faculty of Chemical Engineering and Technology, University of Zagreb , Zagreb , Croatia.
Grace
G
Karminski-Zamola
c Department of Organic Chemistry , Faculty of Chemical Engineering and Technology, University of Zagreb , Zagreb , Croatia.
Marijana
M
Hranjec
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology*; D045744:Cell Line, Tumor; D006801:Humans; D015363:Quinolones / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D001562:Benzimidazoles; D015363:Quinolones
2D and 3D in vitro cytotoxicity assay; amidines; antitumor activity; benzimidazo[1,2-a]quinolines; benzimidazoles