Fluorescence studies on potential antitumor 6-(hetero)arylthieno[3,2-b]pyridine derivatives in solution and in nanoliposomes

Abstract

The photophysical properties (absorption and fluorescence) of four 6-(hetero)arylthieno[3,2-b]pyridine derivatives, the methyl 3-amino-6-(thien-3-yl)thieno[3,2-b]pyridine-2-carboxylate 1, the methyl 3-amino-6-(2,2’-bithienyl-5-yl)thieno[3,2-b]pyridine-2-carboxylate 2, the methyl 3-amino-6-(thien-2-yl)thieno[3,2-b]pyridine-2-carboxylate 3 and the methyl 3-amino-6-(fur-3-yl)thieno[3,2-b]pyridine-2-carboxylate 4, evaluated previously as potential antitumor compounds, were studied in solvents of different polarity. All compounds have reasonable fluorescence quantum yields and exhibit a solvatochromic behaviour. The thienopyridine derivatives were incorporated in lipid membranes of neat egg-yolk phosphatidylcholine (Egg-PC), dipalmitoyl phosphatidylcholine (DPPC), dipalmitoyl phosphatidylglycerol (DPPG) and dioctadecyldimethylammonium bromide (DODAB). Fluorescence measurements indicate that all compounds are mainly located in the lipid bilayer, feeling the transition from the rigid gel phase to the liquid-crystalline phase. The most promising antitumor compounds, the thien-3-yl and the 2,2’-bithienyl-5-yl thienopyridine derivatives 1 and 2, were encapsulated in different nanoliposome formulations, considering future drug delivery applications using liposomes as carriers. Almost all the liposomes with incorporated compounds have diameters lower than 165 nm and generally low polydispersity. The formulation DPPC:DMPG:DSPE-PEG (1:1:0.1) exhibits a small diameter (below 100 nm), low polydispersity and reasonable negative zeta-potential values for both thienopyridines 1 and 2.