Synthesis and characterization of new 1,3,4-thiadiazole derivatives: study of their antibacterial activity and CT-DNA binding.

1,3,4-Thiadiazole molecules (1-4) were synthesized by the reaction of phenylthiosemicarbazide and methoxy cinnamic acid molecules in the presence of phosphorus oxychloride, and characterized with UV, FT-IR, 13C-NMR, and 1H-NMR methods. DFT calculations (b3lyp/6-311++G(d,p)) were performed to investigate the structures' geometry and physiochemical properties. Their antibacterial activity was screened for various bacteria strains such as Enterobacter aerogenes, Escherichia coli ATCC 13048, Salmonella kentucky, Pseudomonas aeruginosa, Klebsiella pneumoniae, Proteus and Gram positive such as Staphylococcus aureus ATCC 25923, Listeria monocytogenes ATCC 7644, Enterococcus faecium, Enterococcus durans, Staphylococcus aureus ATCC, Serratia marcescens, Staphylococcus hominis, Staphylococcus epidermidis, alfa Streptococcus haemolyticus, Enterococcus faecium and found to have an inhibitory effect on Klebsiella pneumoniae and Staphylococcus hominis, while molecules 1, 3 and 4 had an inhibitory effect on Staphylococcus epidermidis and alpha Streptococcus haemolyticus. The experimental results were supported by the docking study using the Kinase ThiM from Klebsiella pneumoniae. All the investigated compounds showed an inhibitory effect for the Staphylococcus epidermidis protein. In addition, the mechanism of the 1-4 molecule interaction with calf thymus-DNA (CT-DNA) was investigated by UV-vis spectroscopic methods.

Synthesis of Cyano-Benzylidene Xanthene Synthons Using a Diprotic Brønsted Acid Catalyst, and Their Application as Efficient Inhibitors of Aluminum Corrosion in Alkaline Solutions.

Novel cyano-benzylidene xanthene derivatives were synthesized using one-pot and condensation reactions. A diprotic Brønsted acid (i.e., oxalic acid) was used as an effective catalyst for the promotion of the synthesis process of the new starting xanthene-aldehyde compound. Different xanthene concentrations (ca. 0.1-2.0 mM) were applied as corrosion inhibitors to control the alkaline uniform corrosion of aluminum. Measurements were conducted in 1.0 M NaOH solution using Tafel extrapolation and linear polarization resistance (LPR) methods. The investigated xanthenes acted as mixed-type inhibitors that primarily affect the anodic process. Their inhibition efficiency values were enhanced with inhibitor concentration, and varied according to their chemical structures. At a concentration of 2.0 mM, the best-performing studied xanthene derivative recorded maximum inhibition efficiency values of 98.9% (calculated via the Tafel extrapolation method) and 98.4% (estimated via the LPR method). Scanning electron microscopy (SEM) was used to examine the morphology of the corroded and inhibited aluminum surfaces, revealing strong inhibitory action of each studied compound. High-resolution X-ray photoelectron spectroscopy (XPS) profiles validated the inhibitor compounds' adsorption on the Al surface. Density functional theory (DFT) and Monte Carlo simulations were applied to investigate the distinction of the anticorrosive behavior among the studied xanthenes toward the Al (111) surface. The non-planarity of xanthenes and the presence of the nitrile group were the key players in the adsorption process. A match between the experimental and theoretical findings was evidenced.

Adsorption behavior and corrosion inhibitive characteristics of newly synthesized cyano-benzylidene xanthenes on copper/sodium hydroxide interface: Electrochemical, X-ray photoelectron spectroscopy and theoretical studies.

Elegant process for synthesis of 3-(7H-dibenzo[c,h]xanthen-7-yl)benzaldehyde (3), as new starting material to create a set of novel xanthene analogues, 2-(3-(7H-dibenzo[c,h]xanthen-7-yl)benzylidene)malononitrile (4), 3-(3-(7H-dibenzo[c,h]xanthen-7-yl)phenyl)-2-cyanoacrylic acid (5), and Ethyl-3-(3-(7H-dibenzo[c,h]xanthen-7-yl)phenyl)-2-cyanoacrylate (6), was achieved starting with available materials under mild conditions. Various concentrations (ca. 0.1-1.0 mM) of the synthesized cyano-benzylidene xanthene derivatives, namely compounds 3-6, were tested as inhibitors to control copper corrosion in alkaline solutions employing polarization and electrochemical impedance spectroscopy (EIS) measurements. Results revealed that the four studied xanthenes derivatives served as efficient (mixed-type) inhibitors. The inhibition efficiency increased with increase in inhibitor concentration.The inhibition performance of studied compounds varied according to their chemical structures. The best inhibitor, compound (5), achieved a maximum inhibition efficiency of 98.7% (calculated from corrosion current densities) and ~ 95% (estimated from charge-transfer resistance values) at a concentration of 1.0 mM. The morphology of the corroded and inhibited copper surfaces was studied by scanning electron microscopy (SEM). The adsorption of the inhibitor molecules was confirmed by high-resolution X-ray photoelectron spectroscopy (XPS) profiles. XPS data were used to compare the inhibition efficiencies exhibited by studied compounds. The oxidation rate of the Cu surface was found to be frivolous, referring to high inhibition efficiency, only in the presence of inhibitor (5), and Cu0 share is 87% of all copper components. The shares of Cu0 were significantly reduced to 43%, 26% and 20% for inhibitors (3), (4) and (6), respectively. These findings go parallel with the results obtained from electrochemical measurements. The quantum-chemical calculations of the investigated molecules were performed to support electrochemical findings, and their correlations with the inhibition efficiency of the synthesized compounds were discussed.

ETM and ANN study for polysubstituted 2H-pyran-2-ones.

The structure glutamate pyruvate transaminase (GPT), glutamate oxaloacetate transaminase (GOT), acid phosphatase (ACP), alkaline phosphatase (ALP) and glutamate dehydrogenase (GlDH) activity relationships of 2H-pyran-2- ones polysubstitutes being a new class of hepatoprotective agents have been investigated by means of the Electronic- Topological Method (ETM) and two Statistical Analysis. Molecular fragments specific for active compounds were calculated for 2H-pyran-2-ones polysubstitutes by applying the ETM. QSAR descriptors such as molecular weight, EHOMO, ELUMO, ΔE, chemical potential, softness, electrophilicity index, dipole moment, etc were calculated. In order to examine the relationship between independent and dependent variables, both Partial Least Squares Regression and ANNs are employed to determine the relationship since the data set consists of highly nonlinearity and multicolinearity. It is observed that ANN has surpassed both PLS2 and PLS1 in terms of better modeling and validation.

Investigation of structure-activity relationship between chemical structure and CCR5 anti HIV-1 activity in a class of 1-[N-(Methyl)-N- (phenylsulfonyl)amino]-2-(phenyl)-4-[4-(substituted)piperidin-1-yl]butane derivatives: the electronic-topological approach.

The relationship between chemical structure and CCR5 anti HIV-1 activity was investigated in the series of 1-[N-(Methyl)-N-(phenylsulfonyl)amino]-2-(phenyl)-4-[4-(substituted) piperidin-1-yl]butanes derivatives including 114 molecules by using the Electron-Topological Method (ETM). In the frameworks of this approach, its input data were taken as the results of conformational and quantum-mechanical calculations. Conformational analysis and quantum-chemical calculations were carried out for each molecule. Then molecular fragments being specific for active molecules and non-active molecules were revealed by using ETM. The result of testing showed the high ability of ETM in predicting the activity and inactivity investigated series. In order to classify and to develop a model for those molecules, cluster and discriminant analyses are conducted. First, cluster analysis is implemented in order to classify similar molecules into the groups. Then, discriminant analysis is used to construct models including descriptors. By doing so, two obtained discriminant functions segregate those molecules into three different groups by using the descriptors called EHOMO, Dipole Moment and SEZPE.

The investigation of structure-activity relationships of tacrine analogues: electronic-topological method.

In this study we investigated the structure-activity relationships by using the Electron- Topological Method (ETM) for a class of AChE inhibitors related to tacrine (9-amino-1,2,3,4-tetrahydroacridine) and 11 H-Indeno-[1,2-b]-quinolin-10-ylamine that tetracyclic tacrine analogues, a drug currently in use for the treatment of the AD. Molecular fragments being specific for active and inactive compounds were revealed by using ETM. The result of testing showed the high ability of ETM in predicting the activity and inactivity in investigated series.