Synthesis and characterization of novel bis(thiosemicarbazone) complexes and investigation of their acetylcholinesterase and glutathione S-transferase activities with in silico and in vitro studies.

In this study, firstly, bis(thiosemicarbazone) ligand [L: 2,2'-(2-(2-(4-methoxyphenyl)hydrazineylidene)cyclohexane-1,3-diylidene)bis(hydrazine-1-carbothioamide)] was synthesized by the condensation reaction of thiosemicarbazide and ketone compound (2-(2-(4-methoxyphenyl)hydrazone)cyclohexane-1,3-dione). The metal complexes were synthesized by the reaction of obtained ligand (L) with CuCl2·2H2O, NiCl2·6H2O, CoCl2·6H2O, and MnCl2·4H2O salts. The structures of synthesized ligand and their complexes were characterized using elemental analysis, IR, UV-Vis, 1H-NMR spectra, 13C-NMR spectra, magnetic susceptibility, mass spectra (LC-MS), thermogravimetry analysis-differential thermal analysis (TGA-DTA), and differential scanning calorimetry techniques. According to the results of the analysis, square plane geometry was suggested for Cu and Co complexes. However, the structures of Ni and Mn complexes were in agreement with octahedral geometry. Molecular docking analysis and pharmacological potential of the compound were evaluated to determine the inhibitory potential against acetylcholinesterase (AChE) and Glutathione-S-transferases (GST) enzymes. The compound exhibited strong binding/docking indices of - 5.708 and - 5.928 kcal/mol for the respective receptors. In addition, L-Ni(II) complex was found to be the most effective inhibitor for AChE enzyme with a Ki value of 0.519. However, with a Ki value of 1.119, L-Cu(II) complex was also found to be an effective inhibitor for the GST enzyme.

Synthesis and examination of 1,2,4-triazine-sulfonamide hybrids as potential inhibitory drugs: Inhibition effects on AChE and GST enzymes in silico and in vitro conditions.

The crucial functions of acetylcholinesterase (AChE) in neurotransmission and glutathione S-transferase (GST) in detoxification and cellular protection underscore their pivotal roles as key enzymes, essential for maintaining the integrity of neurological and cellular homeostasis. For this purpose, a series of 1,2,4-triazine-sulfonamide hybrids (3a-r) was successfully synthesized, and subsequently evaluated for their inhibitory effects on AChE and GST. The investigation was complemented by molecular docking studies and ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) predictions. The synthesized hybrids demonstrated significant promise in inhibiting both AChE and GST activities. Molecular docking analyses provided insights into the interactions between the compounds and the target enzymes, shedding light on potential binding modes and key amino acid residues involved. Furthermore, the study benefited from ADMET predictions, offering valuable information on the compounds' pharmacokinetic properties and potential toxicity. The promising results obtained from this comprehensive approach highlight the potential of these 1,2,4-triazine-sulfonamide hybrids as effective inhibitors of AChE and GST, paving the way for further development and optimization in the pursuit of novel therapeutic agents.

Analysis of bioactive compounds using LC-ESI-MS/MS, cytotoxic, antimicrobial effects, and enzyme activities from Cyclotrichium origanifolium.

Cyclotrichium origanifolium is a medicinal plant belonging to the Lamiaceae family. In this study, phenolic content analysis, antimicrobial effects, and cytotoxic effects of extracts of C. origanifolium were investigated. In the extracts, phenolic compound analysis by the liquid chromatography-electrospray ionization-tandem mass spectrometry method, antimicrobial effect by the minimum inhibition concentration method, and cytotoxic effect on human dermal fibroblasts (HDF), glioblastoma cell (U87), ovarian adenocarcinoma cell (Skov-3), and human colorectal adenocarcinoma cell (CaCo-2) cancer cell lines were investigated. Cytotoxicity analyses were performed by the MTT method. In addition, the GST and AChE enzyme activities of the extracts were also measured. Around 18 compounds were detected in both the methanol and ethanol extract. It was found that the best antimicrobial effect on Gram-negative Pseudomonas aeruginosa was on methanol extract, while the ethanol extract was on Candida albicans fungus (respectively, 2.50 mg/ml, 5.0 µg/ml). A 500 µg/ml of methanol extract has been shown to have cytotoxic activity high effect on HDF cells. GST and AChE activity were found to decrease in a concentration-dependent manner.