Exploration of association of telmisartan with calf thymus DNA using a series of spectroscopic methodologies and theoretical calculation

Telmisartan (TMST) can block selectively and irreversibly an angiotensin II receptor type 1 (AT1), but has no effect on other receptor systems and also induce human prostate cancer cell apoptosis. In this work, domain specific association of TMST with calf thymus DNA was explored through multi-spectral methodologies and theoretical calculation. The results of absorption spectroscopy revealed that TMST interacting with ct-DNA formed the TMST–ct-DNA complex through non-covalent interaction and the association constant ( K a ) was of 2.71 × 10 3  M −1 at 298 K. Based on the thermodynamic analysis , it can be inferred that the interacting TMST with ct-DNA was an enthalpy-driven, spontaneous, and exothermic process due to the Δ G 0  < 0, Δ H 0  < 0, and |Δ H 0 |> T |Δ S 0 | under the studied temperature ranges. The domain interacting forces for interacting TMST with ct-DNA were van der Waals forces and hydrogen bonding interaction due to the Δ H 0  < 0 and Δ S 0  < 0. Meanwhile, the electrostatic and hydrophobic interactions also played a supporting function. Additionally, from experiments and theoretical calculation (molecular docking), it was also confirmed that TMST interacted to a minor groove of the C-G rich region of ct-DNA and resulted in the slight alteration in the secondary structure of ct-DNA whereas the obvious alteration in the geometry of TMST after binding to DNA, indicating that the flexibility of TMST contributed to stabilizing the TMST–ct-DNA complex.