Effect of a Synthesized Amyl-Glycine1, 10-Phenanthroline Platinum Nitrate on Structure and Stability of Human Blood Carrier Protein, Albumin: Spectroscopic and Modeling Approaches.

In the present study, biological evaluation of a new synthesized anti-cancer compound, amyl-glycine1, 10-phenanthroline Platinum nitrate (Pt(II) complex), was investigated at different temperatures by spectroscopic methods (far-UV circular dichroism (CD) and fluorescence) and modeling methods (docking and FRET). Human serum albumin (HSA), one of the vital proteins in drug delivery system in the body, was used as a target protein. The Pt(II) complex is able to quench the intrinsic fluorescence of HSA considerably. Binding and thermodynamic parameters of the interaction between the protein and the ligand were analyzed by fluorescence quenching method. The far-UV CD spectra revealed that the secondary structure of HSA did not show any noticeable change upon interaction with Pt(II) complex at both 25 and 37°C. The calculation of fluorescence resonance energy transfer (FRET) confirmed that quenching mechanism is static, and the observed distance between the donor and acceptor is 1.18 nm. Molecular docking results are in agreement with experimental data suggesting that there is one site on HSA at which Pt(II) complex binds spontaneously. Moreover, docking results together with FRET evaluation illustrated that Pt(II) complex is located near Trp214 at a distance of 1.96 nm. Our experimental and theoretical results indicated that the driving forces for Pt(II) complex interaction with HSA are hydrogen bonding and van der Waals interactions. The combination of molecular docking and spectroscopy methods suggested that use of this new Pt(II) complex as an anti-cancer agent, is an effective innovative approach in cancer chemotherapy providing a better understanding of effects of new designed drugs.

Biological evaluations of newly-designed Pt(II) and Pd(II) complexes using spectroscopic and molecular docking approaches.

To perform biological evaluations of newly-designed Pt(II) and Pd(II) complexes, the present study was conducted with targeted protein human serum albumin (HSA) and HCT116 cell line as model of human colorectal carcinoma. The binding of Pt(II) and Pd(II) complexes to HSA was analyzed using fluorescence spectroscopy and molecular docking. The thermal stability and alterations in the secondary structure of HSA in the presence of Pt(II) and Pd(II) complexes were investigated using the thermal denaturation method and circular dichroism (CD) spectroscopy. The cytotoxicity of the Pt(II) and Pd(II) complexes was studied against the HCT116 cell line using MTT assay. The binding analysis revealed that the fluorescence findings were well in agreement with docking results such that there is only one binding site for each complex on HSA. Binding constants of 8.7 × 103 M-1, 2.65 × 103 M-1, 0.3 × 103 M-1, and 4.4 × 103 M-1 were determined for Pd(II) and Pt(II) complexes (I-IV) at temperature of 25 °C, respectively. Also, binding constants of 1.9 × 103 M-1, 15.17 × 103 M-1, 1.9 × 103 M-1, and 13.1 × 103 M-1 were determined for Pd(II) and Pt(II) complexes (I-IV) at temperature of 37 °C, respectively. The results of CD and thermal denaturation showed that the molecular structure of HSA affected by interaction with Pt(II) and Pd(II) complexes is stable. Cytotoxicity studies represented the growth suppression effect of the Pt(II) and Pd(II) complexes toward the human colorectal carcinoma cell line. Therefore, the results suggest that the new designed Pt(II) and Pd(II) complexes are well promising candidates for use in cancer treatment, particularly for human colorectal cancer. Communicated by Ramaswamy H. Sarma.

A biophysical study on the mechanism of interactions of DOX or PTX with α-lactalbumin as a delivery carrier.

Doxorubicin and paclitaxel, two hydrophobic chemotherapeutic agents, are used in cancer therapies. Presence of hydrophobic patches and a flexible fold could probably make α-Lactalbumin a suitable carrier for hydrophobic drugs. In the present study, a variety of thermodynamic, spectroscopic, computational, and cellular techniques were applied to assess α-lactalbumin potential as a carrier for doxorubicin and paclitaxel. According to isothermal titration calorimetry data, the interaction between α-lactalbumin and doxorubicin or paclitaxel is spontaneous and the K (M-1) value for the interaction of α-lactalbumin and paclitaxel is higher than that for doxorubicin. Differential scanning calorimetry and anisotropy results indicated formation of α-lactalbumin complexes with doxorubicin or paclitaxel. Furthermore, molecular docking and dynamic studies revealed that TRPs are not involved in α-Lac's interaction with Doxorubicin while TRP 60 interacts with paclitaxel. Based on Pace analysis to determine protein thermal stability, doxorubicin and paclitaxel induced higher and lower thermal stability in α-lactalbumin, respectively. Besides, fluorescence lifetime measurements reflected that the interaction between α-lactalbumin with doxorubicin or paclitaxel was of static nature. Therefore, the authors hypothesized that α-lactalbumin could serve as a carrier for doxorubicin and paclitaxel by reducing cytotoxicity and apoptosis which was demonstrated during our in vitro cell studies.