Transition metal complexes with 6-methoxyquinoline as antitumor agents. Biological studies on two and three-dimensional cell cultured models.

CADAVID VARGAS J.F.; VILLA PEREZ, C.; RUIZ, M.C.; LEON, I.E; VALENCIA G.C.; SORIA D.B.; DI VIRGILIO A.L.; ETCHEVERRY S.B.

Congreso; LXI Reunión anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2016

Coordination complexes have been extensively studied asantitumor agents, offering a potential alternative for cancer treatment.􀀤oth, the ligand and the metal play an important role in thepharmacological properties of the complex. This study evaluatesthe effect of 􀀘􀀏methoxyquinoline complexes 􀁙ith copper, zinc andsilver as antitumor agents in 􀀔􀀦 􀀊monolayer􀀋 and a 􀀕􀀦 􀀊multicellularspheroids􀀋 models derived from A􀀗􀀖􀀛 and 􀀯􀀩􀀏􀀘􀀕 cell lines.Ag, Cu and 􀀼n complexes significantly reduced the cell viability􀀊􀀲􀀞􀀒,􀀒􀀒􀀓􀀋 evaluated by the 􀀯TT assay in the 􀀔􀀦 model 􀀊􀀯􀀩􀀏􀀘􀀕􀀜 􀀫C􀀗􀀒 􀀖􀀒.􀀘,􀀗􀀒.􀀙,􀀘􀀕.􀀚 􀁺􀀯, respectively, A􀀗􀀖􀀛􀀜 􀀫C􀀗􀀒 􀀔􀀘.􀀚, 􀀘􀀓.􀀚,􀀔􀀖􀀗.􀀚 􀁺􀀯, respectively􀀋. 􀀯oreover, reactive oxygen species 􀀊􀀴􀀱S􀀋level 􀁙as determined using dihydrorhodamine 􀀓􀀔􀀕 as a fluorescentprobe. 􀀱nly the Cu complex induced 􀀴􀀱S production 􀀊􀀲􀀞􀀒,􀀒􀀒􀀓􀀋.􀀲reliminary studies on synergy of the complexes 􀁙ere performedusing the 􀀯edian􀀏􀀦rug Effect analysis for Cu and 􀀼n complexes atfixed ratio concentrations 􀀊􀀓􀀜􀀓, 􀀓􀀜􀀕 and 􀀓􀀜􀀗􀀋. The affected fraction􀁙as measured after 􀀔􀀖h of incubation. 􀀫t could be observed that 􀀼nand Cu complexes presented a synergic effect at the ratios tested􀁙ith a C􀀫 􀀞􀀓.􀀱n the other hand, spheroids 􀁙ere cultured by theliquid overlay technique and 􀁙ere treated 􀁙ith the complexes for􀀖􀀚h. The spheroids 􀁙ere treated 􀁙ith the Cu and 􀀼n complexes.Ho􀁙ever, this model 􀁙as more resistant and the concentrationstested 􀁙ere raised 􀀔 to 􀀕 times the 􀀫C􀀗􀀒 to reach a significant viabilityreduction 􀀊􀀲􀀞􀀒,􀀒􀀓􀀋. 􀀯orphological changes 􀁙ere observed inthe 􀁙hole range of concentrations using phase contrast microscopy.􀀯oreover, the spheroids treated 􀁙ith lo􀁙 doses 􀁙ere capable tore􀀏attach on the surface. All together, these results suggest that thefour complexes sho􀁙ed a differential effect on the cultured cells. 􀀼nand Cu complexes sho􀁙ed the higher cytotoxic activity in both 􀀔􀀦and 3D models. These compounds are good potential candidatesfor alternative antitumor treatment alone or in combination.