Studies on mechanism of 8-methoxypsoralen–DNA interaction in the dark

The interaction of 8-methoxypsoralen (8-MOP) with calf thymus DNA was studied in darkness at 25 °C and pH 7.4. The enthalpy curve for 8-MOP–DNA interaction was obtained by isothermal titration calorimetry and showed a two-step process for the interaction. According to the spectrophotometric data, it...

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Bibliographic Details
Published in:International journal of pharmaceutics 2002-04, Vol.237 (1), p.47-55
Main Authors: Arabzadeh, A, Bathaie, S.Z, Farsam, H, Amanlou, M, Saboury, A.A, Shockravi, A, Moosavi-Movahedi, A.A
Format: Article
Language:English
Subjects:
8-MOP
Animals
Binding sites
Binding Sites - physiology
Biological and medical sciences
Calorimetry - methods
Cattle
Darkness
DNA
DNA - metabolism
Dose-Response Relationship, Drug
Intercalation
Medical sciences
Methoxsalen - chemistry
Methoxsalen - metabolism
Microcalorimetry
Plant poisons toxicology
Thermodynamics
Toxicology
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Summary:The interaction of 8-methoxypsoralen (8-MOP) with calf thymus DNA was studied in darkness at 25 °C and pH 7.4. The enthalpy curve for 8-MOP–DNA interaction was obtained by isothermal titration calorimetry and showed a two-step process for the interaction. According to the spectrophotometric data, it was suggested that some compaction may occur in the DNA structure at higher [8-MOP] t/[DNA] ratio. Using the fluorescence quenching data, the Scatchard analysis was performed for 8-MOP–DNA interaction at the extended ranges of drug concentration. The results indicated that the first set of binding sites was occupied by 1 mol of drug bound per near eight base pairs of DNA. Also 8-MOP caused the quenching of the fluorescence emission of DNA–ethidium bromide complex. The Scatchard analysis of these data indicated the non-competitive manner for quenching. A non-displacement based quenching mechanism has been suggested for this behavior. The circular dichroism spectra also confirmed the non-intercalative binding of 8-MOP at higher concentrations accompanied by some conformational changes in DNA structure. It has been suggested that at low drug load, 8-MOP binds to DNA as an intercalator, which is an endothermic process, whereas at higher ratios of [8-MOP] t/[DNA], it binds to the outside of DNA, probably in the minor groove and causes some compaction in DNA, which is the exothermic process.
ISSN:0378-5173
1873-3476
DOI:10.1016/S0378-5173(02)00020-0