Synthesis, characterization, molecular modeling studies, and biological evaluation of metal piroxicam complexes (M = Ni(II), Pt(IV), Pd(II), Ag(I)) as antibacterial and anticancer agents.

Four piroxicam metal complexes; NiL2 , PtL2 , PdL2 , and AgL were synthesized and characterized by different techniques with enhanced antibacterial and anticancer activity. Regarding in vitro antimicrobial activity, complex NiL2 displayed potent antibacterial effect against Escherichia coli and Pseudomonas aeruginosa that was 1.9-folds higher than piroxicam (minimum inhibitory concentration [MIC] = 31.85, 65.32 µM), respectively. In case of G+ve bacteria, complex PtL2 had potent activity on Staphylococcus aureus which was 2.1-folds higher than piroxicam (MIC = 43.12 µM), while activity of complex AgL against Enterococcus faecalis was threefolds higher than piroxicam (MIC = 74.57 µM. Complexes PtL2 and PdL2 exhibited higher inhibition of DNA gyrase than piroxicam (IC50 = 6.21 µM) in the range of 1.9-1.7-folds. The in vitro antiproliferative activity depicted that all investigated complexes showed better cytotoxic effect than piroxicam, specifically Pt and Pd complexes which had lower IC50 values than piroxicam on human liver cancer cell line HepG2 by 1.8 and 1.7-folds, respectively. While Pd and Ag complexes showed 2 and 1.6-folds better effect on human colon cancer cell line HT-29 compared with piroxicam. Molecular modeling studies including docking on Stranded DNA Duplex (1juu) and DNA gyrase enzyme (1kzn) that gave good insight about interaction of complexes with target molecules, calculation of electrostatic potential map and global reactivity descriptors were performed.

Assessment of binding interaction to salmon sperm DNA of two antiviral agents and ecofriendly nanoparticles: comprehensive spectroscopic study.

The direct binding of antiviral agents; Daclatasvir and valacyclovir and green synthesized nanoparticles to salmon sperm DNA have been assessed in a comparative study. The nanoparticles were synthesized by the hydrothermal autoclave method and have been fully characterized. The interactive behavior and competitive binding of the analytes to DNA in addition to the thermodynamic properties were deeply investigated by the UV-visible spectroscopy. The binding constants were monitored in the physiological pH conditions to be 1.65 × 106, 4.92 × 105 and 3.12 × 105 for daclatasvir,valacyclovir and quantum dots, respectively. The significant changes in the spectral features of all analytes have proven intercalative binding. The competitive study has confirmed that, daclatasvir, valacyclovir, and the quantum dots have exhibited groove binding. All analytes have shown good entropy and enthalpy values indicating stable interactions. The electrostatic and non-electrostatic kinetic parameters have been determined through studying the binding interactions at different concentrations of KCl solutions. A molecular modelling study has been applied to demonstrate the binding interactions and their mechanisms. The obtained results were complementary and afforded new eras for the therapeutic applications.

Selective Targeting of the Novel CK-10 Nanoparticles to the MDA-MB-231 Breast Cancer Cells.

The main objective of this project was to formulate novel decorated amphiphilic PLGA nanoparticles aiming for the selective delivery of the novel peptide (CK-10) to the cancerous/tumor tissue. Novel modified microfluidic techniques were used to formulate the nanoparticles. This technique was modified by using of Nano Assemblr associated with salting out of the organic solvent using K2HPO4. This modification is associated with higher peptide loading efficiencies, smaller size and higher uniformity. Size, zeta potential & qualitative determination of the adsorbed targeting ligands were measured by dynamic light scattering and laser anemometry techniques using the zeta sizer. Quantitative estimation of the adsorbed targeting ligands was done by colorimetry and spectrophotometric techniques. Qualitative and quantitative uptakes of the various PLGA nanoparticles were examined by the fluorescence microscope and the flow cytometer while the cytotoxic effect of the nanoparticles was measured by the colorimetric MTT assay. PLGA/poloxamer.FA, PLGA/poloxamer.HA, and PLGA/poloxamer.Tf have breast cancer MDA. MB321 cellular uptakes 83.8, 75.43 & 69.37 % which are higher than those of the PLGA/B cyclodextrin.FA, PLGA/B cyclodextrin.HA and PLGA/B cyclodextrin.Tf 80.87, 74.47 & 64.67 %. Therefore, PLGA/poloxamer.FA and PLGA/poloxamer.HA show higher cytotoxicity than PLGA/ poloxamer.Tf with lower breast cancer MDA-MB-231 cell viabilities 30.74, 39.15 & 49.23 %, respectively. The design of novel decorated amphiphilic CK-10 loaded PLGA nanoparticles designed by the novel modified microfluidic technique succeeds in forming innovative anticancer formulations candidates for therapeutic use in aggressive breast cancers.

FTIR spectroscopic study of two isostructural statins: Simvastatin and Lovastatin as authentic and in pharmaceuticals.

A very simple, economic analytical method with few sample pretreatment steps has been developed for quantitation of simvastatin in the presence of its isostructure lovastatin without any interference. It was utilized for easy and complete fine characterization of simvastatin FTIR spectrum from that of lovastatin. Simvastatin has been determined efficiently by the developed method either alone or in mixture with lovastatin giving LOQ values of 0.009 and 0.02% w/w, respectively indicating good sensitivity. Acceptable correlation coefficient values of 0.9975 and 0.9886 alone and in mixture with lovastatin, respectively. The developed spectroscopic method has provided simple and sensitive tool in quality control laboratories for efficient quantitation simvastatin in pharmaceutical tablets with good recoveries.

Salmon sperm DNA binding study to cabozantinib, a tyrosine kinase inhibitor: Multi-spectroscopic and molecular docking approaches.

In the current work, the binding interaction of cabozantinib with salmon sperm DNA (SS-DNA) was studied under simulated physiological conditions (pH 7.4) using fluorescence emission spectroscopy, UV-Vis absorption spectroscopy, viscosity measurement, ionic strength measurement, FT-IR spectroscopy, and molecular modeling methods. The obtained experimental data demonstrated an apparent binding interaction of cabozantinib with SS-DNA. The binding constant (Kb) of cabozantinib with SS-DNA evaluated from the Benesi-Hildebrand plot was equal to 5.79 × 105 at 298 K. The entropy and enthalpy changes (∆S0 and ∆H0) in the binding interaction of SS-DNA with cabozantinib were 44.13 J mol-1 K-1 and -19.72 KJ mol-1, respectively, demonstrating that the basic binding interaction forces are hydrophobic and hydrogen bonding interactions. Results from UV-Vis absorption spectroscopy, competitive binding interaction with rhodamine B or ethidium bromide, and viscosity measurements revealed that cabozantinib binds to SS-DNA via minor groove binding. The molecular docking results revealed that cabozantinib fits into the AT-rich region of the B-DNA minor groove and the binding site of cabozantinib was 4 base pairs long. Moreover, cabozantinib has eight active torsions, implying a high degree of flexibility in its structure, which played a significant role in the formation of a stable cabozantinib-DNA complex.