A new antitumoral Heteroarylaminothieno[3,2-b]pyridine derivative: its incorporation into liposomes and interaction with proteins monitored by fluorescence

• Published in: Photochemical & photobiological sciences Vol. 13; no. 12; pp. 173 - 174
• Main Authors: Costa, C. N. C, Hortelão, A. C. L, Ramos, J. M. F, Oliveira, A. D. S, Calhelha, R. C, Queiroz, M.-J. R. P, Coutinho, P. J. G, Castanheira, E. M. S
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.12.2014
• Subjects: Animals; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; ATP Binding Cassette Transporter, Sub-Family B - chemistry; Biochemistry; Biomaterials; Cattle; Chemistry; Egg Proteins - chemistry; Fluorescence; Fluorescence Polarization; Fluorescence Resonance Energy Transfer; Humans; Hydrophobic and Hydrophilic Interactions; Liposomes - chemistry; Molecular Structure; Nanostructures - chemistry; Physical Chemistry; Plant Sciences; Serum Albumin, Bovine - chemistry; Solvents - chemistry; Spectrometry, Fluorescence; Thienopyridines - chemistry
• ISSN: 1474-905X; 1474-9092
• DOI: 10.1039/c4pp00287c

The fluorescence properties of the new potent antitumoral methyl 3-amino-6-(benzo[ d ]thiazol-2-ylamino)thieno[3,2- b ]pyridine-2-carboxylate in solution and when encapsulated in several different nanoliposome formulations were investigated. The compound exhibits very reasonable fluorescence quantum yields and a solvent sensitive emission in several polar and non-polar media, despite not being fluorescent in protic solvents. Fluorescence anisotropy measurements of the compound incorporated into liposomes revealed that this thienopyridine derivative can be carried in the hydrophobic region of the lipid membrane. Liposome formulations including this antitumor compound are nanometric in size, with a diameter lower than 130 nm and generally low polydispersity, and are promising for future drug delivery developments. The interaction of the compound with bovine serum albumin (BSA) and the multidrug resistance protein MDR1 was monitored by FRET, the compound acting as an energy acceptor. It was observed that the drug had a lower interaction with the MDR1 protein than with the native form of BSA, which is an important result regarding applications of this antitumoral drug. The affinity of an antitumoral thienopyridine derivative to BSA and multidrug resistance protein MDR1 was evaluated by FRET. The compound was encapsulated in liposome formulations.