5351-85-9

Usage

Uses

Used in Biological and Pharmacological Research:
PIPERONAL THIOSEMICARBAZONE is used as a chelating agent for metal ions, facilitating the study of metal ion interactions and their roles in biological systems.
PIPERONAL THIOSEMICARBAZONE is also used as an enzyme inhibitor, allowing researchers to investigate the effects of enzyme inhibition on various biological processes.
Used in Antiviral and Antibacterial Applications:
In the field of virology and microbiology, PIPERONAL THIOSEMICARBAZONE is studied for its potential antiviral properties, offering a possible means to combat viral infections.
Similarly, it is explored for its antibacterial capabilities, which could contribute to the development of new antibiotics to address bacterial resistance.
Used in Drug Development:
PIPERONAL THIOSEMICARBAZONE is utilized as a lead compound in the development of new therapeutic agents, targeting a variety of diseases by leveraging its unique chemical properties and biological activities.

InChI:InChI=1/C9H9N3O2S/c10-9(15)12-11-4-6-1-2-7-8(3-6)14-5-13-7/h1-4H,5H2,(H3,10,12,15)/b11-4+

Upstream product

• 120-57-0 piperonal 
• 79-19-6 thiosemicarbazide 
• 3510-50-7 {3,4-(OCH₂O)2C₆H₃C(H)=N-}2 
• 1157954-32-9 (E)-3-(benzo[d][1,3]dioxol-5-yl)-2-cyanoacryloyl chloride 

Downstream Products

• 28004-60-6 2-amino-5-(3,4-methylenedioxyphenyl)-1,3,4-thiadiazole 
• 106467-52-1 2-Benzo[1,3]dioxol-5-yl-5-(3-m-tolyl-ureido)-[1,3,4]thiadiazole-3-carboxylic acid m-tolylamide 
• 146910-32-9 N-[1-Benzo[1,3]dioxol-5-yl-meth-(E)-ylidene]-N'-[4-(4-nitro-phenyl)-thiazol-2-yl]-hydrazine; hydrobromide 
• 146910-31-8 N-[1-Benzo[1,3]dioxol-5-yl-meth-(E)-ylidene]-N'-(4-biphenyl-4-yl-thiazol-2-yl)-hydrazine; hydrobromide 
• 20159-60-8 N-[1-Benzo[1,3]dioxol-5-yl-meth-(E)-ylidene]-N'-(4-phenyl-thiazol-2-yl)-hydrazine; hydrobromide 
• 146910-29-4 N-[1-Benzo[1,3]dioxol-5-yl-meth-(E)-ylidene]-N'-(4-p-tolyl-thiazol-2-yl)-hydrazine; hydrobromide 
• 146910-26-1 N-[1-Benzo[1,3]dioxol-5-yl-meth-(E)-ylidene]-N'-[4-(4-chloro-phenyl)-thiazol-2-yl]-hydrazine; hydrobromide 
• 146910-28-3 N-[1-Benzo[1,3]dioxol-5-yl-meth-(E)-ylidene]-N'-[4-(4-bromo-phenyl)-thiazol-2-yl]-hydrazine; hydrobromide 
• 146910-30-7 N-[1-Benzo[1,3]dioxol-5-yl-meth-(E)-ylidene]-N'-[4-(4-methoxy-phenyl)-thiazol-2-yl]-hydrazine; hydrobromide 
• 146910-27-2 N-[1-Benzo[1,3]dioxol-5-yl-meth-(E)-ylidene]-N'-[4-(2,4-dichloro-phenyl)-thiazol-2-yl]-hydrazine; hydrochloride 
• 146942-70-3 N-Benzo[1,3]dioxol-5-ylmethyl-N'-(4-phenyl-thiazol-2-yl)-hydrazine 
• 146942-74-7 N-Benzo[1,3]dioxol-5-ylmethyl-N'-(4-p-tolyl-thiazol-2-yl)-hydrazine 
• 146942-71-4 N-Benzo[1,3]dioxol-5-ylmethyl-N'-[4-(4-chloro-phenyl)-thiazol-2-yl]-hydrazine 
• 146942-73-6 N-Benzo[1,3]dioxol-5-ylmethyl-N'-[4-(4-bromo-phenyl)-thiazol-2-yl]-hydrazine 

Relevant academic research and scientific papers

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.

Synthesis, in vitro thymidine phosphorylase activity and molecular docking study of thiadiazole bearing isatin analogs

A series of seventeen analogs (1─17) were synthesized and characterized through different spectroscopic techniques such as 1H, 13CNMR, HR-EI-MS and were evaluated for in vitro thymidine phosphorylase inhibition. All compounds showed excellent to good thymidine phosphorylase activity having IC50 value ranging between 4.10 ± 0.20 and 54.60 ± 1.40?μM when compared with standard drug 7-deazaxanthine (IC50 = 38.68 ± 1.12?μM). Among the series, compounds 1 (IC50 = 8.30 ± 0.30?μM), 6 (IC50 = 6.30 ± 0.10?μM), 11 (IC50 = 8.40 ± 0.30?μM) and 16 (IC50 = 4.10 ± 0.20?μM) were found more potent. Potent compounds were further subjected to molecular docking study to identify their interactions with the active site of amino acid. Structure activity relationship was done for all analogs mostly based on substitution pattern on phenyl and isatin rings. Graphic abstract: [Figure not available: see fulltext.]

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.

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.

Synthesis, biological evaluation and quantitative structure-active relationships of 1,3-thiazolidin-4-one derivatives. A promising chemical scaffold endowed with high antifungal potency and low cytotoxicity

With reference to recent studies reporting on the various biological properties of the thiazolidinone scaffold, we synthesized more than a hundred compounds characterized by a 1,3-thiazolidin-4-one nucleus derivatised at the C2 with a hydrazine bridge linked to (cyclo)aliphatic or hetero(aryl) moieties, and their N-benzylated derivatives. These molecules were assayed as potential anti-Candida agents and they were shown to possess comparable, and in some cases higher biological activity than well-established topical and systemic antimycotic drugs (i.e. clotrimazole, fluconazole, ketoconazole, miconazole, tioconazole, amphotericin B). Compounds endowed with the lowest MICs underwent further testing in order to assess their cytotoxic effect (CC50) on Hep2 cells, which demonstrated their relative safety. Finally, QSAR and 3-D QSAR models were used to predict putative chemical modifications of the 1,3-thiazolidin-4-one scaffold in order to design new and potential more active compounds against Candida spp.

Anti-Candida activity and cytotoxicity of a large library of new N-substituted-1,3-thiazolidin-4-one derivatives

On the basis of the recent findings about the biological properties of thiazolidinones and taking into account the encouraging results about the antifungal activity of some (thiazol-2-yl)hydrazines, new N-substituted heterocyclic derivatives were designed combining the thiazolidinone nucleus with the hydrazonic portion. In details, 1,3-thiazolidin-4-ones bearing (cyclo)aliphatic or (hetero)aromatic moieties linked to the N1-hydrazine at C2 were synthesized and classified into three series according to the aromatic or bicyclic rings connected to the lactam nitrogen of the thiazolidinone. These molecules were assayed for their anti-Candida effects in reference to the biological activity of the conventional topic (clotrimazole, miconazole, tioconazole) and systemic drugs (fluconazole, ketoconazole, amphotericin B). Finally, we investigated the selectivity against fungal cells by testing the compounds endowed with the best MICs on Hep2 cells in order to assess their cell toxicity (CC50) and we noticed that two derivatives were less cytotoxic than the reference drug clotrimazole. Moreover, a preliminary molecular modelling approach has been performed against lanosterol 14-α demethylase (CYP51A1) to rationalize the activity of the tested compounds and to specify the target protein or enzyme.

Novel 3,4-methylenedioxyde-6-X-benzaldehyde-thiosemicarbazones: Synthesis and antileishmanial effects against Leishmania amazonensis

A series of eleven 3,4-methylenedioxyde-6-X-benzaldehyde-thiosemicarbazones (16-27) was synthesised as part of a study to search for potential new drugs with a leishmanicidal effect. The thiosemicarbazones, ten of which are new compounds, were prepared in good yields (85-98%) by the reaction of 3,4-methylenedioxyde-6-benzaldehydes (6-X-piperonal), previously synthesised for this work by several methodologies, and thiosemicarbazide in ethanol with a few drops of H2SO4. These compounds were evaluated against Leishmania amazonensis promastigotes, and derivatives where X = I (22) and X = CN (23) moieties showed impressive results, having IC50 = 20.74 μM and 16.40 μM, respectively. The intracellular amastigotes assays showed IC50 = 22.00 μM (22) and 17.00 μM (23), and selectivity index >5.7 and >7.4, respectively, with a lower toxicity compared to pentamidine (positive control, SI = 4.5). The results obtained from the preliminary QSAR study indicated the hydrophobicity (log P) as a fundamental parameter for the 2D-QSAR linear model. A molecular docking study demonstrated that both compounds interact with flavin mononucleotide (FMN), important binding site of NO synthase.

Synthesis and pharmacological screening of a large library of 1,3,4-thiadiazolines as innovative therapeutic tools for the treatment of prostate cancer and melanoma

Antimitotic agents are widely used in cancer chemotherapy but the numerous side effects and the onset of resistance limit their clinical efficacy. Therefore, with the purpose of discovering more selective and efficient anticancer agents to be administered alone or in combination with traditional drugs, we synthesized a large library of 1,3,4-thiadiazoline analogues, maintaining the pharmacophoric structure of an antiproliferative compound known as K858: this is a new inhibitor of kinesin Eg5, able to induce the mitotic arrest in colorectal cancer cells and in xenograft ovarian cancer cells. We screened 103 compounds to assess their antiproliferative activity on PC3 prostate cancer cell line. Two derivatives, compounds 32 (corresponding to K858) and 33, have shown to be the most effective against prostate tumor cells and also towards two melanoma cell lines (SK-MEL-5 and SK-MEL-28) at low micromolar concentrations, confirming the pharmacological activity of this scaffold and revealing the potential role of 1,3,4-thiadiazolines in the management of cancer.

In vitro and in silico antimalarial activity of 2-(2-hydrazinyl)thiazole derivatives

A series of 2-(2-hydrazinyl)thiazole derivatives with a wide range of substitutions at 2-, 4- and 5-positions were synthesized, characterized and evaluated their inhibitory potentials against plasmodium falciparum, NF54, by in vitro blood stage assay. The compounds, ethyl-4-methyl-2-[(E)-2-[1-(pyridin-2- yl)ethylidene]hydrazin-1-yl]-1,3-thiazole-5-carboxylate, 4d, and 1-{4-methyl-2-[(E)-2-[1-(pyridin-2-yl)ethylidene]hydrazin-1-yl]-1, 3-thiazol-5-yl}ethan-1-one, 5d showed significant antimalarial activity with IC50 values of 0.725 μM and 0.648 μM respectively. To understand the mechanism, the binding interactions between 2-(2-hydrazinyl) thiazole derivatives and trans-2-enoyl acyl carrier protein reductase of P. falciparum were studied through docking studies. The half maximal inhibitory concentration (IC50) through docking studies for the compounds, 4d and 5d were found to be 22.88 μM and 631.84 μM respectively.

Synthesis of a novel series of thiazole-based histone acetyltransferase inhibitors

Acetylation, which targets a broad range of histone and non-histone proteins, is a reversible mechanism and plays a critical role in eukaryotic genes activation/deactivation. Acetyltransferases are very well conserved through evolution. This allows the use of a simple model organism, such as budding yeast, for the study of their related processes and to discover specific inhibitors. Following a simple yeast-based chemogenetic approach, we have identified a novel HAT (histone acetyltransferase) inhibitor active both in vitro and in vivo. This new synthetic compound, 1-(4-(4-chlorophenyl)thiazol-2- yl)-2-(propan-2-ylidene)hydrazine, named BF1, showed substrate selectivity for histone H3 acetylation and inhibitory activity in vitro on recombinant HAT Gcn5 and p300. Finally, we tested BF1 on human cells, HeLa as control and two aggressive cancer cell lines: a neuroblastoma from neuronal tissue and glioblastoma from brain tumour. Both global acetylation of histone H3 and specific acetylation at lysine 18 (H3AcK18) were lowered by BF1 treatment. Collectively, our results show the efficacy of this novel HAT inhibitor and propose the utilization of BF1 as a new, promising tool for future pharmacological studies.