Abstract:
The mechanism of interaction of drugs with potential target and off-target biomolecules such as with DNA enables the development of a rational drug designing system, especially for therapeutic anticancer or anti-tumor drugs. Diclofenac, indomethacin, and mefenamic acid are non-steroidal anti-inflammatory drugs (NSAIDs) that have been tested in this study. These
NSAIDs have diverse biological and pharmacological activities. In vitro methods such as
various biophysical techniques and In silico studies using molecular docking were applied to investigate the binding abilities and mode of binding of these drugs with calf thymus DNA (ct DNA).
The UV-visible absorbance spectra and fluorescence emission profile of the above NSAIDs upon
addition of ct-DNA indicates the formation of a drug–DNA complex. The Wolf shimmer
binding constant (Kb) of diclofenac, indomethacin, and mefenamic acid from UV – visible
experiment was found to be 2.05x104 M-1
, 4.29x104M-1
and 2.73x104 M-1
respectively. The
results of fluorescence experiments revealed the binding constants as 8x10-3 μl ng-1
, 3x10-3 μl
ng-1 and 6x10-3 μl ng-1 for diclofenac, indomethacin and mefenamic acid respectively and these
values are consistent with those of well-known groove binders. The binding constants of all
tested drugs showed the groove binding mode of interaction with ct-DNA. In addition, the
testing of drug-DNA complex for relative specific viscosity and the resulted output images of
the molecular docking experiments further confirmed the effective binding interactions
between ct-DNA and diclofenac, indomethacin, and mefenamic acid.
