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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.


Size distributions obtained by dynamic light scattering (DLS) for DPPC, Egg-PC and DODAB liposomes prepared by the ethanolic injection method.
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Figure 2: Size distributions obtained by dynamic light scattering (DLS) for DPPC, Egg-PC and DODAB liposomes prepared by the ethanolic injection method.

Mentions: The size and size distribution of the liposomes prepared was obtained by DLS. All the liposomes have a mean hydrodynamic radius lower than 150 nm and generally low polydispersity. For Egg-PC and DODAB liposomes, the size distributions are bimodals and broader than for DPPC liposomes, the Egg-PC being the more polydisperse (Figure 2). The ethanolic injection method was described to produce phospholipid small unilamellar vesicles (SV) [12-15]. Accordingly, DPPC and Egg-PC liposomes obtained here are in this category, with a mean diameter of around 90 nm for DPPC and 50 nm for Egg-PC. DODAB liposomes exhibit a significantly larger mean diameter (around 270 nm) than the phospholipid ones. The size of DODAB vesicles strongly depends on the preparation method, sonication and ethanolic injection giving small DODAB vesicles [17,23,24], while injection using chloroform yielded large DODAB vesicles [16]. Besides, spontaneously prepared DODAB liposomes have a much larger size (hydrodynamic radius around 337 nm [25]), being considered giant unilamellar vesicles (GUV). The DODAB liposomes mean diameter obtained here (ca. 270 nm) compares well with the reported value of 249 nm for DODAB SV [16]. In all samples, no experimental evidence of the presence of open bilayer fragments (diameter lower than 10 nm [17]) was obtained (Figure 2).


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)

Size distributions obtained by dynamic light scattering (DLS) for DPPC, Egg-PC and DODAB liposomes prepared by the ethanolic injection method.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Size distributions obtained by dynamic light scattering (DLS) for DPPC, Egg-PC and DODAB liposomes prepared by the ethanolic injection method.
Mentions: The size and size distribution of the liposomes prepared was obtained by DLS. All the liposomes have a mean hydrodynamic radius lower than 150 nm and generally low polydispersity. For Egg-PC and DODAB liposomes, the size distributions are bimodals and broader than for DPPC liposomes, the Egg-PC being the more polydisperse (Figure 2). The ethanolic injection method was described to produce phospholipid small unilamellar vesicles (SV) [12-15]. Accordingly, DPPC and Egg-PC liposomes obtained here are in this category, with a mean diameter of around 90 nm for DPPC and 50 nm for Egg-PC. DODAB liposomes exhibit a significantly larger mean diameter (around 270 nm) than the phospholipid ones. The size of DODAB vesicles strongly depends on the preparation method, sonication and ethanolic injection giving small DODAB vesicles [17,23,24], while injection using chloroform yielded large DODAB vesicles [16]. Besides, spontaneously prepared DODAB liposomes have a much larger size (hydrodynamic radius around 337 nm [25]), being considered giant unilamellar vesicles (GUV). The DODAB liposomes mean diameter obtained here (ca. 270 nm) compares well with the reported value of 249 nm for DODAB SV [16]. In all samples, no experimental evidence of the presence of open bilayer fragments (diameter lower than 10 nm [17]) was obtained (Figure 2).

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.