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European Journal of Medicinal Chemistry Jun 2015Triazoles are heterocyclic compounds which have a five-membered ring of two carbon atoms and three nitrogen atoms. These structures have been interest in the development... (Review)
Review
Triazoles are heterocyclic compounds which have a five-membered ring of two carbon atoms and three nitrogen atoms. These structures have been interest in the development of novel compounds with anticonvulsant, antidepressant, antioxidant, anti-inflammatory, analgesic, antinociceptive, antibacterial, antimycobacterial, antifungal, antiviral, anticancer, anti-parasitic, anti-urease and other activities. Therefore, many researchers have synthesized these compounds as target structures and evaluated their biological activities. This review contains various pharmacological activities of 1,2,4-triazole-3-thiones in one place and it is also the milestone for the new research towards this moiety.
Topics: Animals; Drug Discovery; Humans; Thiones; Triazoles
PubMed: 25563511
DOI: 10.1016/j.ejmech.2014.11.033 -
Molecular Diversity May 2018Dihydropyrimidin-2(1H)-ones/thiones (DHPMs) are important heterocyclic compounds owing to their excellent biological activities and have been widely utilized in... (Review)
Review
Dihydropyrimidin-2(1H)-ones/thiones (DHPMs) are important heterocyclic compounds owing to their excellent biological activities and have been widely utilized in pharmaceutical applications. Recently, numerous DHPM derivatives have been prepared. This review covers the synthesis of DHPMs and improved procedures for the preparation of DHPMs from 1995 to 2016.
Topics: Chemistry Techniques, Synthetic; Pyrimidinones; Solvents; Thiones
PubMed: 29349521
DOI: 10.1007/s11030-017-9806-z -
Organic & Biomolecular Chemistry Sep 20223-Arylquinoxaline-2-thiones were conveniently synthesized three-component oxidative condensation of acetophenones with -phenylenediamines and sulfur in DMSO in the...
3-Arylquinoxaline-2-thiones were conveniently synthesized three-component oxidative condensation of acetophenones with -phenylenediamines and sulfur in DMSO in the presence of piperidine as a catalyst. The products could be readily isolated from the reaction mixture by simple precipitation and washing with methanol. This set of reaction conditions applied to higher homologs of acetophenones as well as benzyl phenyl ketones led to 2,3-di--substituted quinoxalines. Further functionalization of 3-phenylquinoxaline-2-thione reaction on the thione group could be readily performed to provide quinoxaline derivatives in good yields.
Topics: Acetophenones; Catalysis; Dimethyl Sulfoxide; Ketones; Methanol; Phenylenediamines; Piperidines; Quinoxalines; Sulfur; Thiones
PubMed: 36053547
DOI: 10.1039/d2ob01343f -
European Journal of Medicinal Chemistry Jan 2020A new series of thiazole-2(3H)-thiones containing 4-(3,4,5-trimethoxyphenyl) moiety were synthesized as diaryl-heterocylic analogs of combretastatin A-4 with anticancer...
A new series of thiazole-2(3H)-thiones containing 4-(3,4,5-trimethoxyphenyl) moiety were synthesized as diaryl-heterocylic analogs of combretastatin A-4 with anticancer activity. The cytotoxicity evaluation of synthesized compounds against cancer cell lines (A549, MCF-7 and SKOV3) revealed that most of them had potent cytotoxic activity toward all tested cell lines (ICs < 10 μg/mL). Among them, 3-(chlorobenzyl) derivatives 5c and 5d showed the best inhibitory effect on MCF-7 cells (IC values of 1.14 and 2.41 μg/mL, respectively). Furthermore, the ability of tubulin polymerization inhibition and apoptosis induction were evaluated for the promising compounds 5c and 5d. Results suggested that these compounds remarkably inhibit tubulin polymerization and induce apoptosis resulting in cell death. In vitro studies revealed that these compounds had no significant cytotoxicity against normal cells at the concentrations required for growth inhibition of cancer cells. In vitro biding assay and in silico docking study also confirmed the binding of prototype compound to the colchicine binding site of tubulin.
Topics: A549 Cells; Antineoplastic Agents; Apoptosis; Cell Cycle; Cell Line; Cell Proliferation; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Humans; MCF-7 Cells; Molecular Docking Simulation; Molecular Structure; Structure-Activity Relationship; Thiazoles; Thiones; Tubulin; Tubulin Modulators
PubMed: 31669850
DOI: 10.1016/j.ejmech.2019.111784 -
Bioorganic Chemistry Oct 2022A series of alkyl/aryl/aralkylamines or amino acids appended tetrahydro-2H-1,3,5-thiadiazine-2-thiones (4a-i, 5a-g, 6 and 7) were synthesized via one pot domino...
One pot domino synthesis of new 3,5-disubstituted-tetrahydro-2H-1,3,5-thiadiazine-2-thiones (THTTs) as anti-inflammatory and antinociceptive candidates: A proof from in-vivo to in-vitro and in-silico mechanistic studies.
A series of alkyl/aryl/aralkylamines or amino acids appended tetrahydro-2H-1,3,5-thiadiazine-2-thiones (4a-i, 5a-g, 6 and 7) were synthesized via one pot domino synthesis. The synthesis involved reacting alkyl/aryl/aralkylamines or amino acids with carbon disulfide employing basic aqueous medium and further cyclization with formaldehyde and alkyl/aryl/aralkylamines or amino acids. In addition, the carboxy-functionalized 1,3,5-thiadiazine-2-thione 6 was further subjected to esterification. All the structures were confirmed through spectral techniques i.e IR, H NMR, C NMR, and MS analysis. Furthermore, the newly synthesized compounds were biologically assessed via in vitro COX-2 and 5-LOX assays, in vivo anti-nociceptive and anti-inflammatory activities. Among the screened compounds, 6, 5f, and 7 exhibited highest inhibitory potency against COX-2 with IC values of 11.96, 13.54, and 13.93 μM, respectively. Moreover, compounds 6 and 7 exhibited excellent inhibitory potential against 5-LOX with IC values of 14.01 and 14.13 μM. The in-vivo anti-inflammatory bioassay studies showed that compounds 6, 7 and 5f dramatically reduced the paw edema size at 1 h and 3 h time intervals. In the anti-nociceptive activity, compound 6 showed pain protection comparative to Tramadol in all tested time intervals. In addition, studies of molecular docking revealed the compounds binding modes in the allosteric site of COX-2 and active site of 5-LOX, where these compounds exhibited higher binding scores and good binding interactions.
Topics: Amino Acids; Analgesics; Anti-Inflammatory Agents; Cyclooxygenase 2; Molecular Docking Simulation; Structure-Activity Relationship; Thiadiazines; Thiazines; Thiones
PubMed: 35780683
DOI: 10.1016/j.bioorg.2022.105974 -
ACS Chemical Neuroscience Sep 2017The lack of therapies for neurodegenerative diseases arises from our incomplete understanding of their underlying cellular toxicities and the limited number of...
The lack of therapies for neurodegenerative diseases arises from our incomplete understanding of their underlying cellular toxicities and the limited number of predictive model systems. It is critical that we develop approaches to identify novel targets and lead compounds. Here, a phenotypic screen of yeast proteinopathy models identified dihydropyrimidine-thiones (DHPM-thiones) that selectively rescued the toxicity caused by β-amyloid (Aβ), the peptide implicated in Alzheimer's disease. Rescue of Aβ toxicity by DHPM-thiones occurred through a metal-dependent mechanism of action. The bioactivity was distinct, however, from that of the 8-hydroxyquinoline clioquinol (CQ). These structurally dissimilar compounds strongly synergized at concentrations otherwise not competent to reduce toxicity. Cotreatment ameliorated Aβ toxicity by reducing Aβ levels and restoring functional vesicle trafficking. Notably, these low doses significantly reduced deleterious off-target effects caused by CQ on mitochondria at higher concentrations. Both single and combinatorial treatments also reduced death of neurons expressing Aβ in a nematode, indicating that DHPM-thiones target a conserved protective mechanism. Furthermore, this conserved activity suggests that expression of the Aβ peptide causes similar cellular pathologies from yeast to neurons. Our identification of a new cytoprotective scaffold that requires metal-binding underscores the critical role of metal phenomenology in mediating Aβ toxicity. Additionally, our findings demonstrate the valuable potential of synergistic compounds to enhance on-target activities, while mitigating deleterious off-target effects. The identification and prosecution of synergistic compounds could prove useful for developing AD therapeutics where combination therapies may be required to antagonize diverse pathologies.
Topics: Amyloid beta-Peptides; Animals; Animals, Genetically Modified; Caenorhabditis elegans; Clioquinol; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Drug Synergism; Homeostasis; Ions; Metals; Mitochondria; Neurodegenerative Diseases; Neuroprotective Agents; Reactive Oxygen Species; Structure-Activity Relationship; Thiones; Yeasts
PubMed: 28628299
DOI: 10.1021/acschemneuro.7b00187 -
Molecules (Basel, Switzerland) Feb 2012Non-fused 3,6-dihydro-2H-1,3-thiazine-2-thiones constitute a so far rather unexplored class of compounds, with the latest report dating back more than two decades....
Non-fused 3,6-dihydro-2H-1,3-thiazine-2-thiones constitute a so far rather unexplored class of compounds, with the latest report dating back more than two decades. Thiazine-2-thiones contain an endocyclic dithiocarbamate group, which is often found in pesticides, in substrates for radical chemistry and in synthetic intermediates towards thioureas and amidines. We now report the multicomponent reaction (MCR) of in situ-generated 1-azadienes with carbon disulfide. With this reaction, a one-step protocol towards the potentially interesting 3,6-dihydro-2H-1,3-thiazine-2-thiones was established and a small library was synthesized.
Topics: Magnetic Resonance Spectroscopy; Mass Spectrometry; Thiazines; Thiones
PubMed: 22318323
DOI: 10.3390/molecules17021675 -
Journal of Medicinal Chemistry May 2008The synthesis and the X-ray structure of 16a-thiocamptothecin (TCPT), the thiopyridone analog of camptothecin (CPT), are accomplished. The crystal contains two...
The synthesis and the X-ray structure of 16a-thiocamptothecin (TCPT), the thiopyridone analog of camptothecin (CPT), are accomplished. The crystal contains two structurally identical, yet independent molecules. Both of them are connected to other molecules via two intermolecular hydrogen bonds. S-methylation of TCPT leads to the cleavage of the C-ring. The cytotoxic activity of TCPT was evaluated against different human tumor cell lines using CPT as reference compound.
Topics: Antineoplastic Agents; Camptothecin; Cell Line, Tumor; Crystallography, X-Ray; DNA Damage; DNA Topoisomerases, Type I; Humans; Models, Molecular; Thiones
PubMed: 18419110
DOI: 10.1021/jm8001982 -
The Journal of Organic Chemistry Aug 2022A facile access to benzo[]thiazole-2(3)-thiones and benzo[]thiazol-2(3)-ones has been developed through a temperature-controlled intermolecular [3 + 2] annulation of...
A facile access to benzo[]thiazole-2(3)-thiones and benzo[]thiazol-2(3)-ones has been developed through a temperature-controlled intermolecular [3 + 2] annulation of N,N-disubstituted arylhydrazines with CS in the presence of DMSO. This protocol can obviate the prefunctionalization of the starting materials. This direct C-S/C-N bond formation reaction was performed in the absence of any external catalysts, transition metals, bases, ligands, and oxidants with high step economy.
Topics: Metals; Temperature; Thiazoles; Thiones; Transition Elements
PubMed: 35820197
DOI: 10.1021/acs.joc.2c01060 -
Journal of Combinatorial Chemistry Mar 2009We have developed a liquid-phase route for combinatorial synthesis of novel substituted 5-(1,2,4-oxadiazol-5-yl)-3,4-dihydropyrimidine-2(1H)-thiones. Biginelli-type...
We have developed a liquid-phase route for combinatorial synthesis of novel substituted 5-(1,2,4-oxadiazol-5-yl)-3,4-dihydropyrimidine-2(1H)-thiones. Biginelli-type three-component condensation of 1-(3-aryl-1,2,4-oxadiazol-5-yl)acetones, thiourea, and benzaldehydes is shown to result in new 5-(1,2,4-oxadiazol-5-yl)-3,4-dihydropyrimidine-2(1H)-thione heterocyclic system. If salicylaldehydes are used in this reaction, a mixture of 5-(1,2,4-oxadiazol-5-yl)-3,4-dihydropyrimidine-2(1H)-thiones and 11-(1,2,4-oxadiazol-5-yl)-2,3,5,6-tetrahydro-4H-2,6-methano-1,3,5-benzoxadiazocine-4-thiones is formed.
Topics: Combinatorial Chemistry Techniques; Molecular Structure; Oxadiazoles; Pyrimidines; Thiones
PubMed: 19133738
DOI: 10.1021/cc800111h