Limits...
Synthesis, DNA Binding, and Antiproliferative Activity of Novel Acridine-Thiosemicarbazone Derivatives.

de Almeida SM, Lafayette EA, da Silva LP, Amorim CA, de Oliveira TB, Ruiz AL, de Carvalho JE, de Moura RO, Beltrão EI, de Lima Mdo C, de Carvalho Júnior LB - Int J Mol Sci (2015)

Bottom Line: Both hyperchromic and hypochromic effects, as well as red or blue shifts were demonstrated by addition of ctDNA to the derivatives.There was no correlation between DNA-binding and in vitro antiproliferative activity, but the results suggest that DNA binding can be involved in the biological activity mechanism.This study may guide the choice of the size and shape of the intercalating part of the ligand and the strategic selection of substituents that increase DNA-binding or antiproliferative properties.

View Article: PubMed Central - PubMed

Affiliation: Laboratório de Imunopatologia Keizo Asami (LIKA) and Departamento de Bioquímica, Universidade Federal de Pernambuco (UFPE), Recife 50670-901, PE, Brazil. sinara.monica@gmail.com.

ABSTRACT
In this work, the acridine nucleus was used as a lead-compound for structural modification by adding different substituted thiosemicarbazide moieties. Eight new (Z)-2-(acridin-9-ylmethylene)-N-phenylhydrazinecarbothioamide derivatives (3a-h) were synthesized, their antiproliferative activities were evaluated, and DNA binding properties were performed with calf thymus DNA (ctDNA) by electronic absorption and fluorescence spectroscopies. Both hyperchromic and hypochromic effects, as well as red or blue shifts were demonstrated by addition of ctDNA to the derivatives. The calculated binding constants ranged from 1.74 × 10(4) to 1.0 × 10(6) M(-1) and quenching constants from -0.2 × 10(4) to 2.18 × 10(4) M(-1) indicating high affinity to ctDNA base pairs. The most efficient compound in binding to ctDNA in vitro was (Z)-2-(acridin-9-ylmethylene)-N- (4-chlorophenyl) hydrazinecarbothioamide (3f), while the most active compound in antiproliferative assay was (Z)-2-(acridin-9-ylmethylene)-N-phenylhydrazinecarbothioamide (3a). There was no correlation between DNA-binding and in vitro antiproliferative activity, but the results suggest that DNA binding can be involved in the biological activity mechanism. This study may guide the choice of the size and shape of the intercalating part of the ligand and the strategic selection of substituents that increase DNA-binding or antiproliferative properties.

No MeSH data available.


Relative fluorescence intensities of acridine-thiosemicarbazone derivatives 3a (●), 3b (◊), 3c (▲), 3d (▽), 3e (♦), 3f (○), 3g (□) and 3h (▼), upon addition of ctDNA in Tris buffer (0.01 M, pH = 7.6).
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4490484&req=5

ijms-16-13023-f003: Relative fluorescence intensities of acridine-thiosemicarbazone derivatives 3a (●), 3b (◊), 3c (▲), 3d (▽), 3e (♦), 3f (○), 3g (□) and 3h (▼), upon addition of ctDNA in Tris buffer (0.01 M, pH = 7.6).

Mentions: The efficiency of the quenching process was deduced from the plot of the relative emission intensity, I0/I, vs. the DNA concentration (Figure 3) [46]. According to the resulting Stern–Volmer quenching constants, KSV, the most pronounced quenching was demonstrated by 3f derivative (2.18 × 104 M−1). KSV values decreased as follows: 3f > 3h > 3a > 3d > 3g > 3c > 3e > 3b. The emission intensity of the derivatives is quenched upon addition of DNA, most likely due to an efficient electron transfer between the excited ligand and the ctDNA bases. Emission-quenching phenomena reflect the interaction between the derivatives and ctDNA, consistent with the electronic absorption spectroscopy results [47]. Both Stern–Volmer (KSV) and binding constants (Kb) of the derivatives indicate static quenching due to complex formation by the new derivatives and ctDNA. The results indicate that the most efficient compound in binding to ctDNA in vitro was 3f (39.59% hypochromism and the highest Kb, KSV values).


Synthesis, DNA Binding, and Antiproliferative Activity of Novel Acridine-Thiosemicarbazone Derivatives.

de Almeida SM, Lafayette EA, da Silva LP, Amorim CA, de Oliveira TB, Ruiz AL, de Carvalho JE, de Moura RO, Beltrão EI, de Lima Mdo C, de Carvalho Júnior LB - Int J Mol Sci (2015)

Relative fluorescence intensities of acridine-thiosemicarbazone derivatives 3a (●), 3b (◊), 3c (▲), 3d (▽), 3e (♦), 3f (○), 3g (□) and 3h (▼), upon addition of ctDNA in Tris buffer (0.01 M, pH = 7.6).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4490484&req=5

ijms-16-13023-f003: Relative fluorescence intensities of acridine-thiosemicarbazone derivatives 3a (●), 3b (◊), 3c (▲), 3d (▽), 3e (♦), 3f (○), 3g (□) and 3h (▼), upon addition of ctDNA in Tris buffer (0.01 M, pH = 7.6).
Mentions: The efficiency of the quenching process was deduced from the plot of the relative emission intensity, I0/I, vs. the DNA concentration (Figure 3) [46]. According to the resulting Stern–Volmer quenching constants, KSV, the most pronounced quenching was demonstrated by 3f derivative (2.18 × 104 M−1). KSV values decreased as follows: 3f > 3h > 3a > 3d > 3g > 3c > 3e > 3b. The emission intensity of the derivatives is quenched upon addition of DNA, most likely due to an efficient electron transfer between the excited ligand and the ctDNA bases. Emission-quenching phenomena reflect the interaction between the derivatives and ctDNA, consistent with the electronic absorption spectroscopy results [47]. Both Stern–Volmer (KSV) and binding constants (Kb) of the derivatives indicate static quenching due to complex formation by the new derivatives and ctDNA. The results indicate that the most efficient compound in binding to ctDNA in vitro was 3f (39.59% hypochromism and the highest Kb, KSV values).

Bottom Line: Both hyperchromic and hypochromic effects, as well as red or blue shifts were demonstrated by addition of ctDNA to the derivatives.There was no correlation between DNA-binding and in vitro antiproliferative activity, but the results suggest that DNA binding can be involved in the biological activity mechanism.This study may guide the choice of the size and shape of the intercalating part of the ligand and the strategic selection of substituents that increase DNA-binding or antiproliferative properties.

View Article: PubMed Central - PubMed

Affiliation: Laboratório de Imunopatologia Keizo Asami (LIKA) and Departamento de Bioquímica, Universidade Federal de Pernambuco (UFPE), Recife 50670-901, PE, Brazil. sinara.monica@gmail.com.

ABSTRACT
In this work, the acridine nucleus was used as a lead-compound for structural modification by adding different substituted thiosemicarbazide moieties. Eight new (Z)-2-(acridin-9-ylmethylene)-N-phenylhydrazinecarbothioamide derivatives (3a-h) were synthesized, their antiproliferative activities were evaluated, and DNA binding properties were performed with calf thymus DNA (ctDNA) by electronic absorption and fluorescence spectroscopies. Both hyperchromic and hypochromic effects, as well as red or blue shifts were demonstrated by addition of ctDNA to the derivatives. The calculated binding constants ranged from 1.74 × 10(4) to 1.0 × 10(6) M(-1) and quenching constants from -0.2 × 10(4) to 2.18 × 10(4) M(-1) indicating high affinity to ctDNA base pairs. The most efficient compound in binding to ctDNA in vitro was (Z)-2-(acridin-9-ylmethylene)-N- (4-chlorophenyl) hydrazinecarbothioamide (3f), while the most active compound in antiproliferative assay was (Z)-2-(acridin-9-ylmethylene)-N-phenylhydrazinecarbothioamide (3a). There was no correlation between DNA-binding and in vitro antiproliferative activity, but the results suggest that DNA binding can be involved in the biological activity mechanism. This study may guide the choice of the size and shape of the intercalating part of the ligand and the strategic selection of substituents that increase DNA-binding or antiproliferative properties.

No MeSH data available.