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

Abstract

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.

Novel dehydropeptide-based magnetogels containing manganese ferrite nanoparticles as antitumor drug nanocarriers

“…28 Besides, this compound presents a very low affinity for the multidrug resistance protein MDR1, that promotes drug resistance in cells. 29 Curcumin is a natural polyphenolic compound obtained from Curcuma longa roots and known for its role in immune system pathways and intracellular regulation.…”

“…S3 and S4 in Supplementary information). Another feature to take into account is that neither the thienopyridine derivative nor curcumin are emissive in aqueous media, 24,29 both molecules possessing a hydrophobic nature. Figure 7 displays the fluorescence spectra of the three magnetogels incorporating the antitumor thienopyridine derivative, exciting the hydrogelator naproxen moiety (Fig.…”

“…Exciting the naproxen moiety of the hydrogelator molecules, an energy transfer can be observed from the hydrogel to the compound, evidenced by a quenching of the naproxen emission and an increase in the region of compound fluorescence (λ max ∼ 450 nm). 29 It should, however, be noted that the antitumor compound is also directly excited at this wavelength (λ exc =290 nm). The increase in emission at the compound region is only tenuous in the magnetogel with RGD sequence (H3), which can be due to a more hydrophilic environment of the compound promoted by the RGD moiety or a higher quenching effect of drug (FRET acceptor) emission by the nanoparticles in this magnetogel.…”

Magnetoliposomes as carriers for promising antitumor thieno[3,2-b]pyridin-7-arylamines: photophysical and biological studies

“…34 In solid magnetoliposomes, the diarylamines 1 and 2 were incorporated by injection of an ethanolic solution together with the formation of the second lipid layer.…”

“…26,34,42,43 Additional common features with other thienopyridines are the negligible uorescence in protic media (due to hydrogen bonding with this type of solvents), the red shis in emission and band enlargement with increasing solvent polarity, 26,34,42,43 usually attributed to an intramolecular charge transfer (ICT) character of the excited state. 37 The effect is more pronounced for compound 2, exhibiting larger bathochromic shis in polar solvents (a red shi of 120 nm between cyclohexane and dimethylsulfoxide, Table 1).…”