Ex vivo binding studies of the anti-cancer drug noscapine with human hemoglobin: a spectroscopic and molecular docking study†
Noscapine is a non-narcotic alkaloid known to display anti-cancer activity against a wide variety of tumors. Since plasma proteins play the central role in drug transport and targeting, herein we study the binding of noscapine hydrochloride (Nos) with human hemoglobin (Hb), a naturally encapsulated transport molecule. The molecular and biophysical basis of Nos–Hb binding has been investigated by using UV-vis, fluorescence spectroscopy, circular dichroism (CD) and computational methods. The Benesi–Hildebrand binding constant (Kb) and Stern–Volmer constant (KSV) were determined to be 150 M−1 and 5.31 × 103 M−1, respectively. The biomolecular-quenching constant (Kq), 1.06 × 1012 M−1 s−1, indicated a rather static quenching mechanism and negative value for free energy (ΔG −12.5 kJ M−1) which suggests the feasible interaction of Nos with Hb. Job's plot indicates a 1 : 1 binding stoichiometry for Hb–Nos interaction. CD and FTIR spectroscopy studies dictate a change in the secondary structure of Hb upon its interaction with Nos. FRET analysis calculates a distance of 7 nm between Hb and Nos and also confirms the energy transfer between them. Molecular docking studies verified the interacting amino acids and atoms of the Hb–Nos complex and its stability.