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New potential antitumoral fluorescent tetracyclic thieno[3,2-b]pyridine derivatives: interaction with DNA and nanosized liposomes.

Castanheira EM, Carvalho MS, Rodrigues AR, Calhelha RC, Queiroz MJ - Nanoscale Res Lett (2011)

Bottom Line: Fluorescence properties of two new potential antitumoral tetracyclic thieno[3,2-b]pyridine derivatives were studied in solution and in liposomes of DPPC (dipalmitoyl phosphatidylcholine), egg lecithin (phosphatidylcholine from egg yolk; Egg-PC) and DODAB (dioctadecyldimethylammonium bromide).Compound 1, pyrido[2',3':3,2]thieno[4,5-d]pyrido[1,2-a]pyrimidin-6-one, exhibits reasonably high fluorescence quantum yields in all solvents studied (0.20 ≤ ΦF ≤ 0.30), while for compound 2, 3-[(p-methoxyphenyl)ethynyl]pyrido[2',3':3,2]thieno[4,5-d]pyrido[1,2-a]pyrimidin-6-one, the values are much lower (0.01 ≤ ΦF ≤ 0.05).Studies of incorporation of both compounds in liposomes of DPPC, Egg-PC and DODAB revealed that compound 2 is mainly located in the hydrophobic region of the lipid bilayer, while compound 1 prefers a hydrated and fluid environment.

View Article: PubMed Central - HTML - PubMed

Affiliation: Centre of Physics (CFUM), University of Minho, Campus de Gualtar, Braga, 4710-057, Portugal. ecoutinho@fisica.uminho.pt.

ABSTRACT
Fluorescence properties of two new potential antitumoral tetracyclic thieno[3,2-b]pyridine derivatives were studied in solution and in liposomes of DPPC (dipalmitoyl phosphatidylcholine), egg lecithin (phosphatidylcholine from egg yolk; Egg-PC) and DODAB (dioctadecyldimethylammonium bromide). Compound 1, pyrido[2',3':3,2]thieno[4,5-d]pyrido[1,2-a]pyrimidin-6-one, exhibits reasonably high fluorescence quantum yields in all solvents studied (0.20 ≤ ΦF ≤ 0.30), while for compound 2, 3-[(p-methoxyphenyl)ethynyl]pyrido[2',3':3,2]thieno[4,5-d]pyrido[1,2-a]pyrimidin-6-one, the values are much lower (0.01 ≤ ΦF ≤ 0.05). The interaction of these compounds with salmon sperm DNA was studied using spectroscopic methods, allowing the determination of intrinsic binding constants, Ki = (8.7 ± 0.9) × 103 M-1 for compound 1 and Ki = (5.9 ± 0.6) × 103 M-1 for 2, and binding site sizes of n = 11 ± 3 and n = 7 ± 2 base pairs, respectively. Compound 2 is the most intercalative compound in salmon sperm DNA (35%), while for compound 1 only 11% of the molecules are intercalated. Studies of incorporation of both compounds in liposomes of DPPC, Egg-PC and DODAB revealed that compound 2 is mainly located in the hydrophobic region of the lipid bilayer, while compound 1 prefers a hydrated and fluid environment.

No MeSH data available.


Normalized fluorescence spectra (λexc = 360 nm) of compound 1 (4 × 10-6 M) in several solvents; the inset shows the absorption spectrum of 1 in dichloromethane (1 × 10-4 M) as an example.
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Figure 3: Normalized fluorescence spectra (λexc = 360 nm) of compound 1 (4 × 10-6 M) in several solvents; the inset shows the absorption spectrum of 1 in dichloromethane (1 × 10-4 M) as an example.

Mentions: The absorption and fluorescence properties of compounds 1 and 2 were studied in several solvents (Table 1). The normalized fluorescence spectra of compounds 1 and 2 are shown in Figures 3 and 4. The fluorescence emission maximum of both compounds displays a loss of vibrational structure in polar solvents together with a small red shift (Figures 3 and 4), indicating some charge transfer character of the excited state [26]. The red shifts are more significant for compound 2 (Table 1), which may be due to a higher capability of this compound to establish hydrogen bonds with protic solvents (especially with water), due to the presence of the OCH3 group. Compound 1 has significantly higher fluorescence quantum yields (between 20 and 30%) than compound 2 (ΦF between 1 and 5%), showing that the functionalization of the pyridine ring with a triple bond linked to a p-methoxyphenyl group causes a significant enhance of the non-radiative deactivation pathways. The fluorescence quantum yields of compound 1 are also higher than the ones of a benzo[b]thiophene derivative of the same type, a benzothienopyridopyrimidone [27], in which the benzene ring linked to the thiophene is substituted in compound 1 by a pyridine ring. The intrinsic fluorescence of compounds 1 and 2 can be used to monitor interactions with DNA and compounds behaviour when encapsulated in liposomes.


New potential antitumoral fluorescent tetracyclic thieno[3,2-b]pyridine derivatives: interaction with DNA and nanosized liposomes.

Castanheira EM, Carvalho MS, Rodrigues AR, Calhelha RC, Queiroz MJ - Nanoscale Res Lett (2011)

Normalized fluorescence spectra (λexc = 360 nm) of compound 1 (4 × 10-6 M) in several solvents; the inset shows the absorption spectrum of 1 in dichloromethane (1 × 10-4 M) as an example.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3211472&req=5

Figure 3: Normalized fluorescence spectra (λexc = 360 nm) of compound 1 (4 × 10-6 M) in several solvents; the inset shows the absorption spectrum of 1 in dichloromethane (1 × 10-4 M) as an example.
Mentions: The absorption and fluorescence properties of compounds 1 and 2 were studied in several solvents (Table 1). The normalized fluorescence spectra of compounds 1 and 2 are shown in Figures 3 and 4. The fluorescence emission maximum of both compounds displays a loss of vibrational structure in polar solvents together with a small red shift (Figures 3 and 4), indicating some charge transfer character of the excited state [26]. The red shifts are more significant for compound 2 (Table 1), which may be due to a higher capability of this compound to establish hydrogen bonds with protic solvents (especially with water), due to the presence of the OCH3 group. Compound 1 has significantly higher fluorescence quantum yields (between 20 and 30%) than compound 2 (ΦF between 1 and 5%), showing that the functionalization of the pyridine ring with a triple bond linked to a p-methoxyphenyl group causes a significant enhance of the non-radiative deactivation pathways. The fluorescence quantum yields of compound 1 are also higher than the ones of a benzo[b]thiophene derivative of the same type, a benzothienopyridopyrimidone [27], in which the benzene ring linked to the thiophene is substituted in compound 1 by a pyridine ring. The intrinsic fluorescence of compounds 1 and 2 can be used to monitor interactions with DNA and compounds behaviour when encapsulated in liposomes.

Bottom Line: Fluorescence properties of two new potential antitumoral tetracyclic thieno[3,2-b]pyridine derivatives were studied in solution and in liposomes of DPPC (dipalmitoyl phosphatidylcholine), egg lecithin (phosphatidylcholine from egg yolk; Egg-PC) and DODAB (dioctadecyldimethylammonium bromide).Compound 1, pyrido[2',3':3,2]thieno[4,5-d]pyrido[1,2-a]pyrimidin-6-one, exhibits reasonably high fluorescence quantum yields in all solvents studied (0.20 ≤ ΦF ≤ 0.30), while for compound 2, 3-[(p-methoxyphenyl)ethynyl]pyrido[2',3':3,2]thieno[4,5-d]pyrido[1,2-a]pyrimidin-6-one, the values are much lower (0.01 ≤ ΦF ≤ 0.05).Studies of incorporation of both compounds in liposomes of DPPC, Egg-PC and DODAB revealed that compound 2 is mainly located in the hydrophobic region of the lipid bilayer, while compound 1 prefers a hydrated and fluid environment.

View Article: PubMed Central - HTML - PubMed

Affiliation: Centre of Physics (CFUM), University of Minho, Campus de Gualtar, Braga, 4710-057, Portugal. ecoutinho@fisica.uminho.pt.

ABSTRACT
Fluorescence properties of two new potential antitumoral tetracyclic thieno[3,2-b]pyridine derivatives were studied in solution and in liposomes of DPPC (dipalmitoyl phosphatidylcholine), egg lecithin (phosphatidylcholine from egg yolk; Egg-PC) and DODAB (dioctadecyldimethylammonium bromide). Compound 1, pyrido[2',3':3,2]thieno[4,5-d]pyrido[1,2-a]pyrimidin-6-one, exhibits reasonably high fluorescence quantum yields in all solvents studied (0.20 ≤ ΦF ≤ 0.30), while for compound 2, 3-[(p-methoxyphenyl)ethynyl]pyrido[2',3':3,2]thieno[4,5-d]pyrido[1,2-a]pyrimidin-6-one, the values are much lower (0.01 ≤ ΦF ≤ 0.05). The interaction of these compounds with salmon sperm DNA was studied using spectroscopic methods, allowing the determination of intrinsic binding constants, Ki = (8.7 ± 0.9) × 103 M-1 for compound 1 and Ki = (5.9 ± 0.6) × 103 M-1 for 2, and binding site sizes of n = 11 ± 3 and n = 7 ± 2 base pairs, respectively. Compound 2 is the most intercalative compound in salmon sperm DNA (35%), while for compound 1 only 11% of the molecules are intercalated. Studies of incorporation of both compounds in liposomes of DPPC, Egg-PC and DODAB revealed that compound 2 is mainly located in the hydrophobic region of the lipid bilayer, while compound 1 prefers a hydrated and fluid environment.

No MeSH data available.