6292-77-9

Upstream product

• 139-85-5 3,4-dihydroxybenzaldehyde 
• 120-14-9 3,4-dimethoxy-benzaldehyde 
• 79-19-6 thiosemicarbazide 

Downstream Products

• 5427-87-2 2-amino-5-(3,4-dimethoxyphenyl)-1,3,4-thiadiazole 
• 137680-69-4 copper(I) (3,4-dimethoxybenzaldehyde thiosemicarbazone) chloride 
• 137704-94-0 cadmium (3,4-dimethoxybenzaldehyde thiosemicarbazone) diiodide 
• 137704-92-8 cadmium(II) (3,4-dimethoxybenzaldehyde thiosemicarbazone) dichloride 
• 137892-65-0 Co(II) (3,4-dimethoxybenzaldehyde thiosemicarbazone)2 diiodide 
• 137704-97-3 mercury(II) (3,4-dimethoxybenzaldehyde thiosemicarbazone)2 diiodide 
• 137704-90-6 zinc(II) (3,4-dimethoxybenzaldehyde thiosemicarbazone)2 dibromide 
• 137680-68-3 cobalt(II) (3,4-dimethoxybenzaldehyde thiosemicarbazone)2 dibromide 
• 137704-93-9 cadmium(II) (3,4-dimethoxybenzaldehyde thiosemicarbazone) dibromide 
• 137704-96-2 mercury(II) (3,4-dimethoxybenzaldehyde thiosemicarbazone)2 dibromide 
• 137680-70-7 zink (3,4-dimethoxybenzaldehyde thiosemicarbazone)2 dichloride 
• 137680-67-2 cobalt(II) (3,4-dimethoxybenzaldehyde thiosemicarbazone) dichloride 
• 137704-95-1 mercury(II) (3,4-dimethoxybenzaldehyde thiosemicarbazone)2 dichloride 
• 137704-91-7 zinc(II) (3,4-dimethoxybenzaldehyde thiosemicarbazone)2 diiodide 

Relevant academic research and scientific papers

Synthesis, antimicrobial and antioxidant evaluation with in silico studies of new thiazole Schiff base derivatives

A series of nineteen thiazole Schiff base derivatives 2a-2s were synthesized (Scheme 1) and elucidated by spectral analyses (IR, 1H NMR and HRMS). The evaluation of their antimicrobial activities against two gram-positive, two gram-negative, an

Synthesis, characterization, alkaline phosphatase inhibition assay and molecular modeling studies of 1-benzylidene-2-(4-tert- butylthiazol-2-yl) hydrazines

Alkaline phosphatases are homodimeric protein enzymes which removes phosphates from several types of molecules. These catalyze the hydrolysis of monoesters in phosphoric acid which in turn catalyze a transphosphorylation reaction. Thiazoles are a privileged class of heterocyclic compounds which may potentially serve as effective phosphatase inhibitors. In this regard, the present research paper reports the facile synthesis and characterization of substituted 1-benzylidene-2-(4-tert-butylthiazol-2-yl) hydrazines with excellent yields. The synthesized compounds were tested for inhibitory potential against alkaline phosphatases. The compound 1-(4-Hydroxy, 3-methoxybenzylidene)-2-(4-tert-butylthiazol-2-yl) hydrazine (5e) was found to be the most potent inhibitor of human tissue non-alkaline phosphatase in this group of molecules with an IC50 value of 1.09 ± 0.18 μM. The compound 1-(3,4-dimethoxybenzylidene)-2-(4-tert-butylthiazol-2-yl) hydrazine (5d) exhibited selectivity and potency for human intestinal alkaline phosphatase with an IC50 value of 0.71 ± 0.02 μM. In addition, structure activity relationship and molecular docking studies were performed to evaluate their binding modes with the target site of alkaline phosphatase. The docking analysis revealed that the most active inhibitors showed the important interactions within the binding pockets of human intestinal alkaline phosphatase and human tissue non-alkaline phosphatase and may be responsible for the inhibitory activity of the compound towards the enzymes. Therefore, the screened thiazole derivatives provided an outstanding platform for further development of alkaline phosphatase inhibitors.

Design, synthesis and biological assessment of new selective COX-2 inhibitors including methyl sulfonyl moiety

Nonsteroidal anti-inflammatory drugs (NSAIDs) cause peptic lesions in the gastrointestinal mucosa by inhibiting the cyclooxygenase-1 (COX-1) enzyme. Selective COX-2 inhibition causes decreased side effects over current NSAIDs. Therefore, the studies about selective inhibition of COX-2 enzyme are very important for new drug development. The design, synthesis and biological activity evaluation of novel derivatives bearing thiazolylhydrazine-methyl sulfonyl moiety as selective COX-2 inhibitors were aimed in this paper. The structures of synthesized compounds were assigned using different spectroscopic techniques such as 1H NMR, 13C NMR and HRMS. In addition, the estimation of ADME parameters for all compounds was carried out using in silico process. The evaluation of in vitro COX-1/COX-2 enzyme inhibition was applied according to the fluorometric method. According to the enzyme inhibition results, synthesized compounds showed the selectivity against COX-2 enzyme inhibition as expected. Compounds 3a, 3e, 3f, 3g, 3i and 3j demonstrated significant COX-2 inhibition potencies. Among them, compound 3a was found to be the most effective derivative with an IC50 value of 0.140 ± 0.006 μM. Moreover, it was seen that compound 3a displayed a more potent inhibition profile at least 12-fold than nimesulide (IC50 = 1.684 ± 0.079 μM), while it showed inhibitory activity at a similar rate of celecoxib (IC50 = 0.132 ± 0.005 μM). Molecular modelling studies aided in the understanding of the interaction modes between this compound and COX-2 enzyme. It was found that compound 3a had a significant binding property. In addition, the selectivity of obtained derivatives on COX-2 enzyme could be explained and discussed by molecular docking studies.

Assessment of Thiosemicarbazone-Containing Compounds as Potential Antileukemia Agents against P-gp Overexpressing Drug Resistant K562/A02 Cells

P-Glycoprotein (P-gp) overexpression is considered to be the leading cause of multidrug resistance (MDR) and failure of chemotherapy for leukemia. In this study, seventeen thiosemicarbazone-containing compounds were prepared and evaluated as potential ant

Discovery of new coumarin-based lead with potential anticancer, cdk4 inhibition and selective radiotheranostic effect: Synthesis, 2d & 3d qsar, molecular dynamics, in vitro cytotoxicity, radioiodination, and biodistribution studies

Novel 6-bromo-coumarin-ethylidene-hydrazonyl-thiazolyl and 6-bromo-coumarin-thiazolylbased derivatives were synthesized. A quantitative structure activity relationship (QSAR) model with high predictive power r2 = 0.92, and RMSE = 0.44 predicted five compounds; 2b, 3b, 5a, 9a and 9i to have potential anticancer activities. Compound 2b achieved the best ?G of –15.34 kcal/mol with an affinity of 40.05 pki. In a molecular dynamic study 2b showed an equilibrium at 0.8 ? after 3.5 ns, while flavopiridol did so at 0.5 ? after the same time (3.5 ns). 2b showed an IC50 of 0.0136 μM, 0.015 μM, and 0.054 μM against MCF-7, A-549, and CHO-K1 cell lines, respectively. The CDK4 enzyme assay revealed the significant CDK4 inhibitory activity of compound 2b with IC50 of 0.036 μM. The selectivity of the newly discovered lead compound 2b toward localization in tumor cells was confirmed by a radioiodination biological assay that was done via electrophilic substitution reaction utilizing the oxidative effect of chloramine-t.131 I-2b showed good in vitro stability up to 4 h. In solid tumor bearing mice, the values of tumor uptake reached a height of 5.97 ± 0.82%ID/g at 60 min p.i.131 I-2b can be considered as a selective radiotheranostic agent for solid tumors with promising anticancer activity.

In vitro evaluation of new 4-thiazolidinones on invasion and growth of Toxoplasma gondii

Treatments for toxoplasmosis such as pyrimethamine have shown numerous side effects. It has been reported that the likelihood of relapse associated with pyrimethamine-based therapy in patients with HIV and toxoplasmic encephalitis (TE) can have significant implications, even for patients who often develop new lesions in areas of the brain previously free of infection. This led us to research for new agents against Toxoplasma gondii. Recent findings have shown the potent biological activity of 4-thiazolidinones. We proposed to design and synthesize a new series of 2-hydrazono-4-thiazolidinones derivatives to evaluate the in vitro growth inhibition effect on T. gondii. The growth rates of T. gondii tachyzoites in Human Foreskin Fibroblast (HFF) cell culture were identified by two in vitro methodologies. The first one was by fluorescence in which green fluorescent RH parasites and cherry-red fluorescent ME49 parasites were used. The second one was a colorimetric methodology using β-Gal parasites of the RH strain constitutively expressing the enzyme beta-galactosidase. The 4-thiazolidinone derivatives 1B, 2B and 3B showed growth inhibition at the same level of Pyrimethamine. These compounds showed IC50 values of 1B (0.468–0.952 μM), 2B (0.204–0.349 μM) and 3B (0.661–1.015 μM) against T. gondii. As a measure of cytotoxicity the compounds showed a TD50 values of: 1B (60 μM), 2B (206 μM) and 3B (125 μM). The in vitro assays and molecular modeling results suggest that these compounds could act as possible inhibitors of the Calcium-Dependent Protein Kinase 1 of T. gondii. Further, our results support the fact that of combining appropriate detection technologies, combinatorial chemistry and computational biology is a good strategy for efficient drug discovery. These compounds merit in vivo analysis for anti-parasitic drug detection.

Design, synthesis, biological evaluation, QSAR analysis and molecular modelling of new thiazol-benzimidazoles as EGFR inhibitors

Heterocyclic rings such as thiazole and benzimidazole are considered as privileged structures, since they constitute several FDA-approved drugs for cancer treatment. In this work, a new set of 2-(2-(substituted) hydrazinyl)-4-(1-methyl-1H-benzo[d]imidazol-2-yl) thiazoles 4a-q were designed as epidermal growth factor receptor (EGFR) inhibitors and synthesized using concise synthetic methods. The new target compounds have been evaluated in vitro for their suppression activity against EGFR TK. Compounds 4n, 4h, 4i, 4a and 4d exhibited significant potency in comparison with erlotinib which served as a reference drug (IC50, 71.67–152.59 nM; IC50 erlotinib, 152.59 nM). Furthermore, MTT assay revealed that compounds 4j, 4a, 4f, 4h, 4n produced the most promising cytotoxic potency against the human breast cancer cell line (MCF-7) (IC50; 5.96–11.91 μM; IC50 erlotinib; 4.15 μM). Compound 4a showed promising activity as EGFR TK inhibitor as well as anti-breast cancer agent. In addition, 4a induced apoptotic effect and cell cycle arrest at G2/M phase preventing the mitotic cycle in MCF-7 cells. Moreover, 4a upregulated the oncogenic parameters; caspase-3, p53, Bax/Bcl-2 as well as it inhibited the level of PARP-1 enzyme. QSAR study was carried out for the new derivatives and it revealed the goodness of the models. Furthermore, molecular docking studies represented the binding modes of the promising compounds in the active pocket of EGFR.

Design, synthesis, and structure–Activity relationships of thiazole analogs as anticholinesterase agents for alzheimer’s disease

Dementia is a neurological condition commonly correlated with Alzheimer’s disease (AD), and it is seen with many other central nervous system (CNS) disorders. The restricted number of medications is not appropriate to offer enough relief to enhance the quality of life of patients suffering from this symptom; thus, all therapeutic choices should be carefully assessed. In this study, new thiazolylhydrazone derivatives (2a–2l) were designed and synthesized based on the cholinergic hypothesis. Their chemical structures were confirmed by 1H NMR, 13C NMR, and HRMS spectrometric techniques. The ADME (absorption, distribution, metabolism, elimination) parameters of the synthesized compounds were predicted by using QikProp 4.8 software. It was concluded that all compounds presented satisfactory drug-like characteristics. Furthermore, their inhibitory activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in vitro were also tested by modified the Ellman spectrophotometric method. According to the results, all compounds showed a weak inhibitory effect on BChE. On the other hand, most of the compounds (2a, 2b, 2d, 2e, 2g, 2i, and 2j) had a certain AChE inhibitory activity, and the IC50 values of them were calculated as 0.063 ± 0.003, 0.056 ± 0.002, 0.147 ± 0.006, 0.040 ± 0.001, 0.031 ± 0.001, 0.028 ± 0.001, and 0.138 ± 0.005 μM, respectively. Among these derivatives, compound 2i was found to be the most active agent in the series with an IC50 value of 0.028 ± 0.001 μM, which indicated an inhibition profile at a similar rate as the reference drug, donepezil. The potential binding modes of compounds 2a, 2b, 2e, 2g, and 2i with AChE were investigated and compared with each other by the molecular docking studies. The results showed that these compounds were strongly bound up with the AChE enzyme active site with the optimal conformations.

Synthesis and antiviral activity of novel 1,3,4-thiadiazole inhibitors of DDX3x

The human ATPase/RNA helicase X-linked DEAD-box polypeptide 3 (DDX3X) emerged as a novel therapeutic target in the fight against both infectious diseases and cancer. Herein, a new family of DDX3X inhibitors was designed, synthesized, and tested for its inhibitory action on the ATPase activity of the enzyme. The potential use of the most promising derivatives it has been investigated by evaluating their anti-HIV-1 effects, revealing inhibitory activities in the low micromolar range. A preliminary ADME analysis demonstrated high metabolic stability and good aqueous solubility. The promising biological profile, together with the suitable in vitro pharmacokinetic properties, make these novel compounds a very good starting point for further development.

Acetic acid mediated regioselective synthesis of 2,4,5-trisubstituted thiazoles by a domino multicomponent reaction

Acetic acid mediated regioselective synthesis of novel 2,4,5-trisubstituted thiazole derivatives has been reported by a domino reaction of thiosemicarbazide and aldehydes/ketones/isatin, to generate thiosemicarbazones (in situ) followed by addition of arylglyoxal and active methylene/activated C-H acids/pyrazole/indole in ethanol at 80 °C. The products are obtained in high yields by a simple work up. Metal free, short reaction time and high yields are some merits of this methodology.