Probing the combination of erlotinib hydrochloride, an anticancer drug, and human serum albumin: Spectroscopic, molecular docking, and molecular dynamic analyses.

Human serum albumin (HSA) is a globular and monomeric protein in plasma that transports many drugs and compounds. Binding of some drugs to HSA can lead to changes in its stability and biological function. We investigated the binding interactions between erlotinib hydrochloride (Erlo) and HSA. Erlo is used to treat lung, pancreatic, and some other cancers. Experimental data showed that the fluorescence emission of the protein was quenched by Erlo using a static quenching mechanism. The calculation of the binding constant, Kb (1.57 × 105 M-1 at 300 K), confirmed the existence of a moderate binding interaction between Erlo and HSA. The interaction was enthalpy driven, spontaneous, and exothermic. The calculated thermodynamic parameters in agreement with simulation and molecular docking data showed that van der Waals and hydrogen bond forces played an important role in the interaction process. Molecular docking results indicated that Erlo has more affinity to bind to subdomain IIA (site I) of HSA. Molecular dynamics simulation analysis showed that the protein is stable in the presence of Erlo under simulation conditions.

Improving the adsorption potential of chitosan for heavy metal ions using aromatic ring-rich derivatives.

This study describes the simple preparation process of modified chitosan (CS) that can effectively adsorb lead ion in the aqueous medium. To design this adsorbent with high binding sites, the Schiff base ligand with three aromatic rings, 3,3-diphenylpropylimine methyl benzaldehyde (PPIMB), is synthesized. The PPIMB forms several new binding sites in modified CS by making a new imine bond with free NH2 in CS structure. The structural and physicochemical characteristics of the magnetically modified chitosan (MCS-PPIMB) are evaluated by FTIR, XRD, SEM, EDX, DLS, VSM, and TG techniques. The effect of some factors, such as pH, collision time, adsorbent dosage, and initial concentration of Pb(II), is investigated on the adsorption capacity of the adsorbent. The adsorption capacity of MCS-PPIMB against Pb(II) is obtained 230.48 mg/g. The adsorption behavior of MCS-PPIMB is fitted efficiently by the Langmuir isotherm model. The fluorometric studies show that the adsorbent has a sharp emission peak at 698 nm, and Pb(II) ion can quench the fluorescence emission of MCS-PPIMB at low concentration. The theoretical studies confirm the strong binding energy of the Pb atom with aromatic rings and imine groups of the MCS-PPIMB.

Catalytic activity and structural changes of catalase in the presence of Levothyroxine and Isoxsuprine hydrochloride.

Two drugs that pregnant women (with hypothyroidism) may use during pregnancy include Isoxsuprine hydrochloride (ISO) and levothyroxine (LEV); ISO to reduce uterine contractions and LEV for the treatment of hypothyroidism. In the current work, we explored the mechanism of binding affinity between the above drugs and antioxidant enzyme Bovine Liver Catalase (BLC). The experimental results confirmed that both drugs could bind with BLC to form drug-BLC complexes but LEV showed a higher binding affinity toward enzyme. The binding constants of LEV-and ISO-BLC were 0.42 × 105 and 0.13 × 104 M-1 at 310 K, respectively. LEV enhanced the catalase activity but the enzymatic activity of BLC reduced gradually in the presence of ISO. Both drugs were able to induce conformational changes in the BLC structure. The results of the molecular docking investigations confirmed the experimental data and showed that the main binding forces in the LEV-BLC and ISO-BLC systems were hydrogen bond and hydrophobic force. The best binding site of both drugs on BLC is located at a cavity among the wrapping domain, N-Terminal arm, and ß-barrel.

New porphyrins: synthesis, characterization, and computational studies.

New trans-A2B2-porphyrins substituted at phenyl positions were synthesized from 4-methylphthalic acid as a starting material through sequential multistep reactions. These macrocycles were characterized by 1H NMR, 13C NMR, 19F NMR, 1H-1H COSY NMR, and MALDI-TOF mass spectrometry. Computational studies were performed on the porphyrins to investigate various factors such as structural features, electronic energy, energy gaps, and aromaticity. Energy band gap values of these compounds especially N-hydroxyphthalimide-functionalized porphyrins were small that makes them as good candidates for solar cell systems and photocatalysis. Relationships between electronic energies and aromaticity of the compounds were then investigated. The data indicated that the aromaticity features at the center of two series of these compounds (fluorinated and non-fluorinated porphyrins) were in the opposite manner.

Preparation, characterization and comparison of biological potency in two new Zn(II) and Pd(II) complexes of butanedione monoxime derivatives.

A novel Schiff base ligand (2-iminothiophenol-2,3-butanedione monoxime, ITBM) and its complexes with Pd(II) and Zn(II) metal ions ([M(ITBM)2]Cl2) were synthesized and characterized in the present study. The formulated complexes were evaluated for in vitro antioxidant activity as radical scavengers against 1,1-diphenyl-2-picrylhydrazyl radicals (DPPH•). According to the results, antioxidant activity of Pd complex (IC50=36 mg L-1) was more effective than that of Zn(II) complex (IC50=72 mg L-1). Biophysical techniques along with computational modeling were employed to examine the binding of these complexes with human serum albumin (HSA) as the model protein. The trial findings revealed an interaction between Schiff base complexes and HSA with a modest binding affinity [Kb=6.31(±0.11)×104 M-1 for Zn(II) complex and 0.71(±0.05)×104 M-1 for Pd(II) complex at 310 K]. An intense fluorescence quenching of protein through a static quenching mechanism was occurred due to the binding of both complexes to HSA. Hydrogen bonds and van der Waals forces in both examined systems were the main stabilizing forces in the development of drug-protein complex. Based on far-UV-CD observations, the content of α-helical structure in the protein was reduced through induction by both complexes. Analysis of protein-ligand docking demonstrated binding of the two Schiff base complexes to residues placed in the IIA subdomain of HSA. In addition, Zn complex with HSA showed a stronger binding ability than that of Pd complex.Communicated by Ramaswamy H. Sarma.

Synthesis and characterization of an adsorptive Schiff base-chitosan nanocomposite for removal of Pb(II) ion from aqueous media.

A new magnetic chitosan-(2-iminothiophenol methyl)benzaldehyde Schiff base-based adsorbent (MCS-ITMB) was synthesized to be effective adsorbent for adsorption of Pb+2 from aqueous solutions. The adsorbent was characterized by Fourier transform infrared spectroscopy (FT-IR), scanning electron microscope (SEM), energy dispersive X-ray spectroscopy (EDX), dynamic light scattering (DLS), vibrating sample magnetometer (VSM) and X-ray Diffraction (XRD). Batch adsorption experiments were done under various conditions, such as adsorbent dose, pH, and contact time. The equilibrium data were fitted to Langmuir and Freundlich isotherm models. The maximum monolayer capacity obtained from the Langmuir isotherm was 134.10 mg/g. The MCS-ITMB was found to be regenerated effectively up to five efficient cycles of adsorption/desorption processes. The mechanism for Pb+2 adsorption onto MCS-ITMB involved the interactions of N, O and S atoms and also aromatic rings with heavy metal followed by their adsorption on the MCS-ITMB.

Synthesis, characterization, X-ray crystal structure, DFT calculation and antibacterial activities of new vanadium(IV, V) complexes containing chelidamic acid and novel thiourea derivatives.

Three new thiourea ligands derived from the condensation of aroyl- and aryl-isothiocyanate derivatives with 2,6-diaminopyridine, named 1,1'-(pyridine-2,6-diyl)bis(3-(benzoyl)thiourea) (L1), 1,1'-(pyridine-2,6-diyl)bis(3-(2-chlorobenzoyl)thiourea) (L2) and 1,1'-(pyridine-2,6-diyl)bis(3-(4-chlorophenyl)thiourea) (L3), their oxido-vanadium(IV) complexes, namely [VO(L1('))(H2O)] (C1), [VO(L2('))(H2O)] (C2) and [VO(L3('))(H2O)] (C3), and also, dioxo-vanadium(V) complex containing 4-hydroxy-2,6-pyridine dicarboxylic acid (chelidamic acid, H2dipic-OH) and metformin (N,N-dimethylbiguanide, Met), named [H2Met][VO2(dipic-OH)]2·H2O (C4), were synthesized and characterized by elemental analysis, FTIR and (1)H NMR and UV-visible spectroscopies. Proposed structures for free thiourea ligands and their vanadium complexes were corroborated by applying geometry optimization and conformational analysis. Solid state structure of complex [H2Met][VO2(dipic-OH)]2·H2O (triclinic, Pi) was fully determined by single crystal X-ray diffraction analysis. In this complex, metformin is double protonated and acted as counter ion. The antibacterial properties of these compounds were investigated in vitro against standard Gram-positive and Gram-negative bacterial strains. The experiments showed that vanadium(IV) complexes had the superior antibacterial activities than novel thiourea derivatives and vanadium(V) complex against all Gram-positive and Gram-negative bacterial strains.