Synthesis, biological evaluation and in silico studies of novel thiadiazole-hydrazone derivatives for carbonic anhydrase inhibitory and anticancer activities.

Thiadiazole and hydrazone derivatives (5a-5i) were synthesized and their chemical structures were verified and described by 1H NMR, 13C NMR, and HRMS spectra. Three cancer cell lines (MCF-7, MDA, and HT-29) and one healthy cell line (L929) were used to test the cytotoxicity activity of synthesized compounds as well as their inhibitory activity against carbonic anhydrase I, II and IX isoenzymes. Compound 5d (29.74 µM) had a high inhibitory effect on hCA I and compound 5b (23.18 µM) had a high inhibitory effect on hCA II. Furthermore, compound 5i was found to be the most potent against CA IX. Compounds 5a-5i, 5b and 5i showed the highest anticancer effect against MCF-7 cell line with an IC50 value of 9.19 and 23.50 µM, and compound 5d showed the highest anticancer effect against MDA cell line with an IC50 value of 10.43 µM. The presence of fluoro substituent in the o-position of the phenyl ring increases the effect on hCA II, while the methoxy group in the o-position of the phenyl ring increases the activity on hCA I as well as increase the anticancer activity. Cell death induction was evaluated by Annexin V assay and it was determined that these compounds cause cell death by apoptosis. Molecular docking was performed for compounds 5b and 5d to understand their biological interactions. The physical and ADME properties of compounds 5b and 5d were evaluated using SwissADME.

Synthesis and molecular modelling of thiadizole based hydrazone derivatives as acetylcholinesterase and butyrylcholinesterase inhibitory activities.

Some novel substituted thiazolylhydrazine derivatives were designed, synthesized and their inhibitory effects on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes and antioxidant activities were investigated. The structures of the synthesized compounds were determined using different spectroscopic techniques such as 1H-NMR, 13C-NMR, and HRMS. According to the enzyme inhibition results, the synthesized compounds showed selectivity against BuChE enzyme inhibition. Compounds 5e, 5g, 5i and 5j displayed significant BuChE inhibition potencies. Among them, compound 5i was found to be the most effective derivative with an IC50 value of 56.01 ± 0.054 µM. In addition, their antioxidant properties were evaluated in vitro through the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. For compounds 5e, 5g, 5i and 5j in silico molecular docking and 100 ns molecular dynamics simulations studies against the BuChE enzyme were performed to determine possible protein-ligand interactions and stability. DFT-D3 study was performed to stabilize of compounds 5e, 5g, 5i and 5j both in gas and solvent medium and investigated their electronic properties. Of all geometries, that of DMSO is the lowest one.

Synthesis of new benzimidazole derivatives containing 1,3,4-thiadiazole: their in vitro antimicrobial, in silico molecular docking and molecular dynamic simulations studies.

A series of some new benzimidazole-1,3,4-thiadiazoles was synthesized. The structures of target substances were confirmed by using 1H-NMR and 13С-NMR spectroscopy, mass spectrometry and elemental analysis. The synthesized compounds were evaluated for antimicrobial activity against six bacterial strains namely Escherichia coli (ATCC 25922), Klebsiella pneumoniae (ATCC 13883), Pseudomonas aeruginosa (ATCC 27853), Enterococcus faecalis (ATCC 2942), Bacillus subtilis (ATCC 6633), Staphylococcus aureus (ATCC 29213)and four fungal strains namely Candida albicans (ATCC 24433), Candida krusei (ATCC 6258), Candida parapsilosis (ATCC 22019) and Candida glabrata (ATCC 9). Antimicrobial data revealed that compounds 4f and 4i with MIC of < 0.97 µg/mL were found to be most effective against E. coli. Among the studied molecules, compounds 4f and 4i showed the best antifungal activity with MIC value of 1.95 µg/mL. Additionally, docking studies were performed towards the most promising compounds 4f and 4i, in the active site of DNA gyrase revealing strong interactions. A molecular dynamics (MD) simulation analysis was also used to investigate the dynamic nature, binding interaction, and protein-ligand stability.

Synthesis and evaluation of anti-acetylcholinesterase activity of some benzothiazole based new piperazine-dithiocarbamate derivatives.

In this present study some benzothiazole derivatives bearing piperazine and thiocarbamate moieties were synthesized and their potential anticholinesterase properties were investigated. A set of 30 new compounds of 2-[(6-substituted benzothiazol-2-yl)amino]-2-oxoethyl 4-substituted piperazine-1-carbodithioate derivatives were synthesized by reacting 2-chloro-N-(6-substituted benzothiazole-2-yl)acetamide derivatives derivatives and sodium salts of appropriate N,N-disubstituted dithiocarbamic acids in acetone. The structures of the obtained compounds were elucidated using FT-IR, (1)H-NMR and MS spectral data and elemental analyses result. Each derivative was evaluated for its ability to inhibit acetylcholinesterase (AChE) using a modificated Ellman's spectrophotometric method. Some of the compounds can be identified as anticholinesterase agents due to their inhibitory effect when compared with Donepezil. Compounds with dimethylamino ethyl or dimethylamino propyl substituents were defined as the anticholinesterase active compounds.

N-(chroman-4-ylidene)aryloxyacetohydrazones: synthesis and antimicrobial activity.

In this study, some N-(chroman-4-ylidene)phenoxyacetohydrazone and N-(chroman-4-ylidene)phenoxyacetohydrazone compounds were synthesized. Structure of the compounds were identified by using IR, H NMR and MASS spectral data and by elemental analysis. Particularly, some compounds showed interesting antimycobacterial activities.

Synthesis of some triazolyl-benzofuranamine derivatives.

The synthesis of some triazoly-benzofuranamine derivatives starting from 2-chloro-N-(5-substituted-2,3-dihydro-3-benzofuryl)acetamides and 3-(aryloxyalkyl)-4-ethyl/phenyl-5-mercapto-1,2,4-triazoles is described. The chemical structures of the compounds were elucidated. The prepared compounds were tested for herbicidal activity.

Synthesis and analgesic activity of some triazoles and triazolothiadiazines.

The synthesis of some triazoles and triazolothiadiazines starting from (5,6,7,8-tetrahydronaphthalen-2-yl)oxyacetic acid is described. The chemical structure of the compounds were elucidated by analytical, IR, 1H NMR and mass spectral studies. Some of the newly synthesized compounds were tested for analgesic activity and compounds 5b, 5c, and 5d exhibited promising analgesic activity.

Synthesis and antimicrobial activity of some pyridinyliminothiazoline derivatives.

The synthesis of some pyridinyliminothiazoline derivatives starting from N-pyridine-N'-phenyl thiourea and alpha-halogenoacetophenones is described. The chemical structures of the compounds were elucidated. The prepared compounds were tested for antimicrobial activity.

The synthesis of some triazolylphenothiazine derivatives and their antidepressant and anxiolytic activities.

10-[2-(4-Amino-5-mercapto-1,2,4-triazol-3-yl)ethyl]phenothiazine was prepared starting from 3-(10-phenothiaziniyl)propionic acid. This new triazole was employed in the synthesis of some Schiff bases and N-bridged heterocycles. All the newly synthesized compounds were characterized by analytical, IR, 1H-NMR and MASS Spectral studies. Some of the newly synthesized compounds were screened for their antidepressant and anxiolytic activities.

Modification of intracellular free calcium in cultured F2408 embryo fibroblasts by 3-substituted-2-thiohydantoin derivatives.

3-substituted-2-thiohydantoin derivatives were synthesized and their structures elucidated by IR, 1H-NMR spectroscopy and elemental analysis. The cytotoxicity of the 2-thiohydantoin derivatives to rat embryo fibroblasts (F2408) in vitro was determined, and the effects of these compounds on intracellular free Ca2+, [Ca2+]i, were measured by spectrofluorophotometry. Cytotoxicity was determined by metabolic reduction of a tetrazolium salt to a formazan dye (MTT assay). Compounds 4 and 7 showed cytotoxic activity, with IC50 values in the range of 1-1.2 microM. Introduction of either chlorophenyl, metoxyphenyl, nitrophenyl or benzyl groups at C-3 resulted in concentration-dependent cytotoxic effects. Compounds 1-6 at 1 microM or more significantly increased [Ca2+]i in a dose-dependent manner in the cultured fibroblasts. This action may have been mediated through intracellular calcium stores.