Abdulilah Ece

Redox pathways of aliskiren based on experimental and computational approach and its voltammetric determination

Electrochemical behavior of aliskiren (ALS) was studied via experimental electrochemical methods and theoretical calculations performed at B3LYP/6-31+G (d)//AM1. Cyclic voltammetry studies were carried out based on the adsorption-controlled reversible reduction at ca. -1.5 V on hanging mercury drop electrode (HMDE) and irreversible electrochemical oxidation of ALS at ca. 1.0 V on glassy carbon electrode (GCE), vs. Ag/AgCl, KCl (3.0 mol L-1), in Britton-Robinson buffer at pH 10 and 8, respectively. According to computational and experimental findings, ALS is expected to be oxidized irreversibly at benzylic position and reduced reversibly at amide carbonyl groups. Voltammetric methods with and without adsorptive stripping mode were developed and validated for quantification of ALS in different samples. Limits of detection and of quantification for ALS were 6.3 × 10-8 and 2.1 × 10-7 mol L-1 for differential pulse voltammetry on HMDE and 1.2 × 10-8 and 3.9 × 10-8 mol L-1 for square-wave cathodic adsorptive stripping voltammetry. The methods were successfully applied to assay the drug in tablets and human serum with good recoveries, between 91.7 and 102.3%, having relative standard deviation less than 10%.

A computational insight into acetylcholinesterase inhibitory activity of a new lichen depsidone.

Abstract Acetylcholinesterase (AChE) inhibitors are yet the best drugs currently available for the management of Alzheimer’s disease. The recent phytochemical investigation has led to the isolation of a new depsidone 1 with moderate AChE activity (1 μg). This work was focused on its electronic properties analysed using commercially available programs. Both the active depsidone molecule 1 and galanthamine showed to have higher HOMO energies than the inactive depsidones 2–4, isolated from the same lichen species. However, the amino depsidone derivative 7, whose structure was proposed using computational approaches, is expected to be more active AChE inhibitor than the depsidone 1, due to the improved HOMO energy value. In addition, the molecular docking study indicated that the compound 7 has ability to make the well-known interactions of potent AChE inhibitors with the enzyme active site. The data presented herein support the design of novel AChE inhibitors based on the depsidone scaffold.

Synthesis, characterization, preliminary SAR and molecular docking study of some novel substituted imidazo[2,1-b][1,3,4]thiadiazole derivatives as antifungal agents

The aim of this study was to synthesize imidazo[2,1-b][1,3,4]thiadiazole derivatives, characterize them with various spectroscopic methods and investigate their antifungal activities. 2-Αmino-1,3,4-thiadiazole derivatives 2a, b were synthesized by reacting nitrile compounds 1a, b with thiosemicarbazide (yields 75 and 88%). We then synthesized imidazo[2,1-b][1,3,4]thiadiazole derivatives 4–21, the target compounds, from the reactions of 2-amino-1,3,4-thiadiazole derivatives 2a, b with phenacyl bromide derivatives 3 (yields 52–69%). The structures of all synthesized compounds were characterized by infrared, 1H nuclear magnetic resonance, 13C nuclear magnetic resonance, elemental analysis and mass spectroscopy and X-ray diffraction analysis was also used for the compounds 7, 8, 10, and 17. Subsequently, in vitro antifungal activity tests were applied to all synthesized compounds. Inhibition zones, percentages of inhibition and LD50 doses were determined. Most of the synthesized compounds exhibited good antifungal activity against plant pathogens. Molecular docking and electronic properties calculations were carried out in order to see the potential binding conformations of the ligands and the effect of the substituents on the activities. Docking score successfully reflects the activity of the most active compound 10, which was found to have the lowest octanol/water partition coefficient and high HOMO energy value. The combination of experimental and computational work show that all the synthesized compounds have promising activities and might serve as novel drug candidates.

Design, Synthesis, SAR and Molecular Modeling Studies of Novel Imidazo[2,1‐b][1,3,4]Thiadiazole Derivatives as Highly Potent Antimicrobial Agents

In this study, a novel series of phenyl substituted imidazo[2,1‐b][1,3,4]thiadiazole derivatives were synthesized, characterized and explored for antibacterial activity against Gram‐negative Escherichia coli, Gram‐positive Staphylococcus aureus and Bacillus subtilis and antifungal activity against Candida albicans. Most of the synthesized compounds exhibited remarkable antimicrobial activities, some of which being ten times more potent than positive controls. The most promising compound showed excellent activity with MIC value of 0.03 μg/ml against both S. aureus and B. subtilis (MIC values of positive compound Chloramphenicol are 0.4 μg/ml and 0.85 μg/ml, respectively). Furthermore, structure‐activity relationship was also investigated with the help of computational tools. Some physicochemical and ADME properties of the compounds were calculated too. The combination of electronic structure calculations performed at PM6 level and molecular docking simulations using Glide extra‐precision mode showed that the hydrophobic nature of keto aryl ring with no electron withdrawing substituents at para position enhances activity while electron‐donating substituents at the second aryl ring is detrimental to activity.

In vitro Antibacterial and Antifungal Activity and Computational Evaluation of Novel Indole Derivatives Containing 4-Substituted Piperazine Moieties

This work was partially supported by Faculty of Pharmacy, Ankara University, research Fund.