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 ( K b ) and Stern-Volmer constant ( K SV ) were determined to be 150 M −1 and 5.31 × 10 3 M −1 , respectively. The biomolecular-quenching constant ( K q ), 1.06 × 10 12 M −1 s −1 , indicated a rather static quenching mechanism and negative value for free energy (Δ G −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. Noscapine binds human hemoglobin spontaneously forming a stable complex that affects noscapine's ADMET profile, bioavailability and toxicity.