Marta Struga

Disubstituted thiourea derivatives and their activity on CNS: Synthesis and biological evaluation

A series of new thiourea derivatives of 1,2,4-triazole have been synthesized. The difference in structures of obtained compounds are directly connected with the kind of isothiocyanate (aryl/alkyl). The (1)H NMR, (13)C NMR, MS methods were used to confirm structures of obtained thiourea derivatives. The molecular structure of (1, 17) was determined by an X-ray analysis. Two of the new compounds (8 and 14) were tested for their pharmacological activity on animal central nervous system (CNS) in behavioural animal tests. The results presented in this work indicate the possible involvement of the serotonergic system in the activity of 8 and 14. In the case of 14 is also a possible link between its activity and the endogenous opioid system. All obtained compounds were tested for antibacterial activity against gram-positive cocci, gram-negative rods and antifungal activity. Compounds (1, 2, 5, 7, 9) showed significant inhibition against gram-positive cocci. Microbiological evaluation was carried out over 20 standard strains and 30 hospital strains. Selected compounds (1-13) were examined for cytotoxicity, antitumor, and anti-HIV activity.

4-Azatricyclo[5.2.2.02,6]undecane-3,5,8-triones as Potential Pharmacological Agents

A series of twenty six arylpiperazine and aminoalkanol derivatives of 4-aza-tricyclo[5.2.2.02,6]undecane-3,5,8-trione have been prepared. The synthesized compounds were evaluated for their cytotoxicity and anti-HIV-1 activity in MT-4 cells.

Synthesis and Evaluation of in Vitro Biological Activity of 4-Substituted Arylpiperazine Derivatives of 1,7,8,9-Tetrachloro- 10,10-dimethoxy-4-azatricyclo(5.2.1.0 2,6 )dec-8-ene-3,5-dione

A series of twenty arylpiperazine derivatives of 1,7,8,9-tetrachloro-10,10-dimethoxy-4-azatricyclo[5.2.1.02,6]dec-8-ene-3,5-dione have been prepared. These derivatives were tested in vitro with the aim of identifying novel lead compounds active against emergent and re-emergent human and cattle infectious diseases (AIDS, hepatitis B and C, tuberculosis, bovine viral diarrhea). In particular, these compounds were evaluated in vitro against representatives of different virus classes, such as a HIV-1 (Retrovirus), a HBV (Hepadnavirus) and the single-stranded RNA+ viruses Yellow fever virus (YFV) and Bovine viral diarrhea virus (BVDV), both belonging to the Flaviridae. Compounds 2c, 2g and 3d showed a modest activity against CVB-2. The molecular structures of the starting imide 1 and one of propyl-piperazine derivatives, 3b, have been determined by an X-ray crystallography study.

Synthesis and microbiological activity of thiourea derivatives of 4-azatricyclo[5.2.2.0(2,6)]undec-8-ene-3,5-dione.

A series of thiourea derivatives of 4-azatricyclo[5.2.2.02,6]undec-8-ene-3,5-dione were synthesized. The compounds were investigated for antibacterial activity, including Gram-positive cocci, Gram-negative rods, and antifungal activity. Compounds 1b, 2b, 4b showed significant inhibition against Gram-positive cocci. Research was carried out over 10 standard strains and 20 hospital strains. Synthesized compounds were evaluated for their cytotoxicity and anti-HIV-1 activity in MT-4 cells.

Synthesis and Antimicrobial Activity of 4-Chloro-3-Nitrophenylthiourea Derivatives Targeting Bacterial Type II Topoisomerases.

A series of novel 4‐chloro‐3‐nitrophenylthiourea derivatives were synthesized and evaluated for their antimicrobial, antibiofilm and tuberculostatic activities. Most of compounds exhibited high antibacterial activity against both standard and hospital strains (MIC values 0.5–2 μg/mL), as compared to Ciprofloxacin. Derivatives with 3,4‐dichlorophenyl (11) and 3‐chloro‐4‐methylphenyl (13) substituents were the most promising towards Gram‐positive pathogens. Both of them exhibited antibiofilm potency and effectively inhibited the formation of biofilms of methicillin‐resistant and standard strains of Staphylococcus epidermidis. Two N‐alkylthioureas (20, 21) showed twofold to fourfold increase in in vitro potency against isolates of Mycobacterium tuberculosis, as compared to Isoniazid. An action of 7, 10, 11, 13, 20 and 21 against activity of topoisomerases isolated from Staphylococcus aureus was studied. Synthesized compounds were found as non‐genotoxic.

Vibrational spectroscopy (FT-IR and Laser-Raman) investigation, and computational (M06-2X and B3LYP) analysis on the structure of 4-(3-fluorophenyl)-1-(propan-2-ylidene)-thiosemicarbazone.

In this study, the experimental and theoretical vibrational spectral analysis of 4-(3-fluorophenyl)-1-(propan-2-ylidene)-thiosemicarbazone have been carried out. The experimental FT-IR (4000-400 cm(-1)) and Laser-Raman spectra (4000-100 cm(-1)) have been recorded for the solid state samples. The theoretical vibrational frequencies and the optimized geometric parameters (bond lengths and angles) have been calculated for gas phase using density functional theory (DFT/B3LYP: Becke, 3-parameter, Lee-Yang-Parr) and M06-2X (the highly parametrized, empirical exchange correlation function) quantum chemical methods with 6-311++G(d,p) basis set. The diversity in molecular geometry of fluorophenyl substituted thiosemicarbazones has been discussed based on the X-ray crystal structure reports and theoretical calculation results from the literature. The assignments of the vibrational frequencies have been done on the basis of potential energy distribution (PED) analysis by using VEDA4 software. A good correlation was found between the computed and experimental geometric and vibrational data. In addition, the highest occupied (HOMO) and lowest unoccupied (LUMO) molecular orbital energy levels and other related molecular energy values of the compound have been determined using the same level of theoretical calculations.

Binding modes of chain arylpiperazines to 5-HT1a, 5-HT2a and 5-HT7 receptors.

An overview of docking models of chain arylpiperazines to different subtypes of serotonin receptors belonging to the GPCR family is presented. The theory of a ligand-receptor interaction has been briefly summarized. The review covers more than twenty models, beginning with the early models of a ligand interaction with the 5-HT1A and 5-HT2A receptor, and ending with a ligand-5-HT7 receptor docking studies.

Antimicrobial activity of 10-(diphenylmethylene)-4-azatricyclo[5.2.1.02,6]dec-8-ene-3,5-dione derivatives

Antibacterial and antifungal activity of 10-(diphenylmethylene)-4-azatricyclo[5.2.1.02,6]dec-8-ene-3,5-dione derivatives were examined by the disk diffusion method (growth inhibition zone diameter in agar medium). The minimal inhibitory concentrations (MICs) for the most active agents were determined. Title compounds were also evaluated in vitro against HIV-1 virus and their cytotoxicity was determined. Aminoalkanol derivatives exhibited activity against the majority of microorganisms studied.

Biological evaluation of novel 1,4-dithiine derivatives as potential antimicrobial agents

The preparation of twelve aminoalkanol derivatives of 2,3-dihydro-5H-[1,4]dithiino[2,3-c]pyrrole-5,7(6H)-dione was described. Newly obtained compounds, as well as their propyl and butyl analogues, were evaluated in vitro against selected viruses. Selected derivatives were tested for their antibacterial and antifungal activity. Compounds 3h, 3j, 4b and 5a–d showed moderate to significant protections against CVB-2, HSV-1 and YFV viruses. The molecular structures of 4a, 5c and 5g were determined by an X-ray analysis.

Synthesis of new derivatives of 2,2-dimethyl-2,3-dihydro-7-benzo[b]furanol with potential antimicrobial activity

A series of 13 new ether-linked derivatives of 2,2-dimethyl-2,3-dihydro-7-benzo[b]furanol have been designed and synthesized. Ten of them were evaluated for their potential antimicrobial activity against some Gram-positive and Gram-Negative bacteria and fungi of the Candida species.