In Vitro Cytotoxicity and Interaction of Noscapine with Human Serum Albumin: Effect on Structure and Esterase Activity of HSA

Abstract

Noscapine is effective to inhibit cellular proliferation and induced apoptosis in nonsmall cell, lung, breast, lymphoma, and prostate cancer. It also shows good efficiency to skin cancer cells. In the current work, we studied the mechanism of interaction between the anticancer drug noscapine (NOS) and carrier protein human serum albumin (HSA) by using a variety of spectroscopic techniques (fluorescence spectroscopy, time-resolved fluorescence, UV−visible, fluorescence resonance energy transfer (FRET), Fourier transform infrared (FTIR), and circular dichroism (CD) spectroscopy), electrochemistry (cyclic voltammetry), and computational methods (molecular docking and molecular dynamic simulation). The steady-state fluorescence results showed that fluorescence intensity of HSA decreased in the presence of NOS via a static quenching mechanism, which involves ground state complex formation between NOS and HSA. UV−visible and FRET results also supported the fluorescence result. The corresponding thermodynamic result shows that binding of NOS with HSA is exothermic in nature, involving electrostatic interactions as major binding forces. The binding results were further confirmed through a cyclic voltammetry approach. The FRET result signifies the energy transfer from Trp214 of HSA to the NOS. Molecular site marker, molecular docking, and MD simulation results indicated that the principal binding site of HSA for NOS is site I. Synchronous fluorescence spectra, FTIR, 3D fluorescence, CD spectra, and MD simulation results reveal that NOS induced the structural change in HSA. In addition, the MTT assay study on a human skin cancer cell line (A-431) was also performed for NOS, which shows that NOS induced 80% cell death of the population at a 320 μM concentration. Moreover, the esterase-like activity of HSA with NOS was also done to determine the variation in protein functionality after binding with NOS.

Inhibitory effect of corosolic acid on α‐glucosidase: kinetics, interaction mechanism, and molecular simulation

“…The possibility of interplay between CRA and α ‐glucosidase in vivo was therefore predictable. All values of n (0.86, 0.80, 0.73) were close to 1 at the experimental temperatures, indicating that the α ‐glucosidase–CRA complex formed at an approximate molar ratio of 1:1 and that CRA might only occupy one binding site in α ‐glucosidase …”

“…All values of n (0.86, 0.80, 0.73) were close to 1 at the experimental temperatures, indicating that the -glucosidase-CRA complex formed at an approximate molar ratio of 1:1 and that CRA might only occupy one binding site in -glucosidase. 46,47 The interaction forces between CRA and -glucosidase can be evaluated after the calculation of the thermodynamic parameters. The non-covalent interaction between small molecules and enzymes mainly includes electrostatic interaction, a hydrogen bond, hydrophobic forces, and Van der Waals forces.…”

Binding mechanism of maltol with catalase investigated by spectroscopy, molecular docking, and enzyme activity assay

“…The Stern‐Volmer plots at different temperatures (298 K, 303 K, and 310 K) are shown in Figure S3A, and the results summarized in Table S1. These results clearly suggested that maltol quenched the fluorescence of CAT through static quenching mechanism as the values of K sv continuously decreased with an increase in temperature …”

Integration of Molecular Docking and In Vitro Studies: A Powerful Approach for Drug Discovery in Breast Cancer

“…As several studies have reported the ability of NOS to inhibit the growth of tumor cells and to activate apoptosis, there are ongoing phase I/II clinical trials for cancer management, but not for BC [40]. Maurya et al [41] studied the interaction between NOS and carrier protein HSA using different techniques, including in vitro approaches and computational methods. The cytotoxicity findings by MTT assay indicated that NOS has good potential in cancer.…”

“…The cytotoxicity findings by MTT assay indicated that NOS has good potential in cancer. Meanwhile, the in silico results showed that the main binding site for NOS was site I (subdomain II A) of HSA [41].…”