Synthesis,Characterization, and Biological Evaluation of Some Novel Thiosemicarbazones as Possible Antibacterial and Antioxidant Agents

Abstract

The synthesis and characterization of 18 novel thiosemicarbazones have been investigated as part of a research program on development of compounds with antibacterial and antioxidant activities. Among the tested compounds, 2-(4-hydroxybenzylidene)-N-[4-(trifluoromethoxy)phenyl]hydrazine carbothioamide (3g) and 2-(thiophen-2-ylmethylidene)-N-[4-(morpholin-4-yl)phenyl]hydrazine carbothioamide (4b) showed excellent inhibition potency at low concentration (0.5 μg/mL) against Gram-positive pathogens (Enterococcus faecalis and Staphylococcus aureus). All tested compounds were also found to possess antioxidant activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical and 2,2’-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical cation.

[Supplementary materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements for the following free supplemental files: Additional text, tables, and figures.]     

Novel Thiosemicarbazone Derivatives: In Vitro and In Silico Evaluation as Potential MAO-B Inhibitors

MAO-B inhibitors are frequently used in the treatment of neurodegenerative diseases such as Parkinson’s and Alzheimer’s. Due to the limited number of compounds available in this field, there is a need to develop new compounds. In the recent works, it was shown that various thiosemicarbazone derivatives show hMAO inhibitory activity in the range of micromolar concentration. It is thought that benzofuran and benzothiophene structures may mimic structures such as indane and indanone, which are frequently found in the structures of such inhibitors. Based on this view, new benzofuran/benzothiophene and thiosemicarbazone hybrid compounds were synthesized, characterized and screened for their hMAO-A and hMAO-B inhibitory activity by an in vitro fluorometric method. The compounds including methoxyethyl substituent (2b and 2h) were found to be the most effective agents in the series against MAO-B enzyme with the IC₅₀ value of 0.042 ± 0.002 µM and 0.056 ± 0.002 µM, respectively. The mechanism of hMAO-B inhibition of compounds 2b and 2h was investigated by Lineweaver–Burk graphics. Compounds 2b and 2h were reversible and non-competitive inhibitors with similar inhibition features as the substrates. The K_i values of compounds 2b and 2h were calculated as 0.035 µM and 0.046 µM, respectively, with the help of secondary plots. The docking study of compound 2b and 2h revealed that there is a strong interaction between the active sites of hMAO-B and analyzed compound.     

Preconcentration and separation of copper (II) with solvent extraction using N,N′-bis(2-hydroxy-5-bromo-benzyl)1,2 diaminopropane

Preconcentration and separation with solvent extraction of Cu(II) from aqueous solution using N,N′-bis(2-hydroxy-5-bromo-benzyl)1,2 diaminopropane (H₂L) as the new extractant has been studied. Separation of Cu(II) from other metal ions such as Cd(II), Ni(II), Zn(II), Pb(II), Cr(III), Co(II) and Mn(II) at aqueous solutions of various pH values and complexing agent H₂L, has been described. The possible extraction mechanism and the compositions of the extracted species have been determined. The separation factors for these metals using this reagent are reported while efficient methods for the separation of Cu(II) from other metal ions are proposed. From the loaded organic phase, Cu(II) stripping was carried out in one stage with different mineral acid solutions. The stripping efficiency was found to be quantitative in case of HNO₃ and HCl. From quantitative evaluation of the extraction equilibrium data, it has been deduced that the complex extracted is the simple 1:1 chelate, CuL. The extraction constant has a value of logK_ex=−4.05±0.04.     

Synthesis and Antinociceptive Effect of Some Thiazole-Piperazine Derivatives: Involvement of Opioidergic System in the Activity

In this study, we aimed to design and synthesize novel molecules carrying both the thiazole and piperazine rings in their structures and to investigate their antinociceptive activity. Targeted compounds were obtained by reacting thiosemicarbazide derivative and appropriate 2-bromoacetophenone in ethanol. The structures of the obtained compounds were determined using data from various spectroscopic methods (IR, ¹H-NMR, ¹³C-NMR, and LCMSMS). Experimental data from in vivo tests showed that test compounds 3a–3c, 3f, and 3g (50 mg/kg) significantly prolonged reaction times of animals in tail-clip and hot-plate tests compared to the controls, indicating that these compounds possess centrally mediated antinociceptive activities. Furthermore, these compounds reduced the number of writhing behaviors in the acetic acid-induced writhing tests, showing that the compounds also possess peripheral antinociceptive activity. In the mechanistic studies, naloxone pre-treatments abolished the antinociceptive activities of compounds 3a–3c, 3f, and 3g, indicating that opioidergic mechanisms were involved in their antinociceptive effects. Molecular docking studies demonstrating significant interactions between the active compounds and µ- and δ-opioid receptor proteins supported the pharmacological findings. This study is the first showing that molecules designed to bear thiazole and piperazine moieties together on their structure exert centrally and peripherally mediated antinociceptive effects by activating the opioid system.     

Effects of solvent casted poly (lactic acid)/poly(ethylene glycol)/paraben derivative triazine films on antibacterial performance and cytotoxicity

A series of poly(lactic acid) (PLA) films that including fully paraben substituted triazine derivatives having anti-bacterial properties have been prepared by utilizing the solvent-casting method. PLA as biodegradable polymer, poly(ethylene glycol) (PEG) as a plasticizing agent and s-triazine molecules (TA01, TA02, TA03, TA04, and TA05) behaving as an anti-bacterial component have been utilized in the experiments. The influence of TA compounds on the antibacterial performance of PLA/PEG films was investigated for the first time against Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus) bacteria via the contact active method. TA01-03-05 incorporated PLA/PEG films gave the best results against E.coli bacteria and log10 reductions of these films were 0.78, 0.64, and 0.65 respectively. The effect of TA compounds on the cell viability was investigated against cancer and non-cancerous cell lines using an MTS assay. The results showed that TA compounds had a positive effect on cell growth in non-cancerous cells, while they had a negative effect on cell growth in cancer cells. Furthermore, the addition of TA considerably increased the decomposition temperatures from 349° to 361° and char yield from 0.65 for PLA/PEG film to 2.3 for PLA/PEG/TA05. All of the films had good transparency and low opacity which was 7.2 for pure PLA used for control and the maximum opacity value was 11.2 observed for PLA/PEG/01. TA03 and TA04 caused a decrement of water vapor permission when compared to PLA/PEG films from 1439 to 749 and 664. It was also observed that pure PLA/PEG film lost weight rapidly over time during degradation tests. On the other hand, weight loss wasn't observed in PLA/PEG/TA films. This study focused on demonstrating the use of our new, flexible PLA/PEG derivatives in food and medical packaging.     

Sonochemical synthesis and chracterization of Mn3O4 nanoparticles

We report on the synthesis of Mn₃O₄ nanoparticles (NPs) using a novel sonochemical method without requiring any pH adjustment. Synthesized material was identified as tetragonal hausmannite crystal structure model of Mn₃O₄ from XRD analysis. Crystallite size was estimated from x-ray line profile fitting to be 17±5 nm. FTIR analysis revealed stretching vibrations of metal ions in tetrahedral and octahedral coordination confirming the crystal structure. TEM analysis revealed a dominantly cubic morphology of NPs with an average size of ∼20 nm. Magnetic evaluation revealed a blocking temperature, T _B of 40 K above which the material behaves paramagnetic. Asymmetric coercive field is attributed to the interaction between ferromagnetic Mn₃O₄ and antiferromagnetic Mn oxide at the surface of nanoparticles.      

Fractional optimal control problem of a distributed system in cylindrical coordinates

In this work, Fractional Optimal Control Problem (FOCP) of a Distributed system is investigated in cylindrical coordinates. Axis-symmetry naturally arises in the problem formulation. The fractional time derivative is described in the Riemann-Liouville (RL) sense. The performance index of a FOCP is considered as a function of state and control variables and system dynamics are given as a Partial Fractional Differential Equation (PFDE). The method of separation of variables is used to find the solution of the problem. Eigenfunctions are used to eliminate the terms containing space parameters and to define the problem in terms of a set of generalized state and control variables. For numerical computations, Grünwald-Letnikov (GL) approach is used. A time-invariant example is considered to demonstrate the effectiveness of the formulation. The comparison of analytical and numerical solutions is given using simulation results and also it can be seen that analytical and numerical results converge each other. In addition, simulation results for different values of order of derivative, time discretizations and eigenfunctions are analyzed.     

The isomorphism problem for uniserial modules over an arbitrary ring

Abstract

First, we give a partial solution to the isomorphism problem for uniserial modules of finite length with the help of the morphisms between these modules. Later, under suitable assumptions on the lattice of the submodules, we give a method to partially solve the isomorphism problem for uniserial modules over an arbitrary ring. Particular attention is given to the natural class of uniserial modules defined over algebras given by quivers.