Thiazole Derivatives Research Articles

The therapeutic value of thiazole and thiazolidine derivatives in Alzheimer's disease: a systematic literature review.

Alzheimer's disease (AD) is a common neurodegenerative disease and the fifth leading cause of death among the elderly. The development of drugs for AD treatment is based on inhibiting cholinesterase (ChE) activity and inhibiting amyloid-beta peptide and tau protein aggregations. Many in vitro findings have demonstrated that thiazole-and thiazolidine-based compounds have a good inhibitory effect on ChE and other elements involved in the AD pathogenicity cascade. In the present review, we collected available documents to verify whether these synthetic compounds can be a step forward in developing new medications for AD. A systematic literature search was performed in major electronic databases in April 2021. Twenty-eight relevant in vitro and in vivo studies were found and used for data extraction. Findings demonstrated that thiazole-and thiazolidine-based compounds could ameliorate AD's pathologic condition by affecting various targets, including inhibition of ChE activity, amyloid-beta, and tau aggregation in addition to cyclin-dependent kinase 5/p25, beta-secretase-1, cyclooxygenase, and glycogen synthase kinase-3β. Due to multitarget effects at micromolar concentration, this review demonstrated that these synthetic compounds could be considered promising candidates for developing anti-Alzheimer drugs.

A review on potential heterocycles for the treatment of glioblastoma targeting receptor tyrosine kinases.

Glioblastoma, the most aggressive form of brain tumor, poses significant challenges in terms of treatment success and patient survival. Current treatment modalities for glioblastoma include radiation therapy, surgical intervention, and chemotherapy. Unfortunately, the median survival rate remains dishearteningly low at 12-15 months. One of the major obstacles in treating glioblastoma is the recurrence of tumors, making chemotherapy the primary approach for secondary glioma patients. However, the efficacy of drugs is hampered by the presence of the blood-brain barrier and multidrug resistance mechanisms. Consequently, considerable research efforts have been directed toward understanding the underlying signaling pathways involved in glioma and developing targeted drugs. To tackle glioma, numerous studies have examined kinase-downstream signaling pathways such as RAS-RAF-MEK-ERK-MPAK. By targeting specific signaling pathways, heterocyclic compounds have demonstrated efficacy in glioma therapeutics. Additionally, key kinases including phosphatidylinositol 3-kinase (PI3K), serine/threonine kinase, cytoplasmic tyrosine kinase (CTK), receptor tyrosine kinase (RTK) and lipid kinase (LK) have been considered for investigation. These pathways play crucial roles in drug effectiveness in glioma treatment. Heterocyclic compounds, encompassing pyrimidine, thiazole, quinazoline, imidazole, indole, acridone, triazine, and other derivatives, have shown promising results in targeting these pathways. As part of this review, we propose exploring novel structures with low toxicity and high potency for glioma treatment. The development of these compounds should strive to overcome multidrug resistance mechanisms and efficiently penetrate the blood-brain barrier. By optimizing the chemical properties and designing compounds with enhanced drug-like characteristics, we can maximize their therapeutic value and minimize adverse effects. Considering the complex nature of glioblastoma, these novel structures should be rigorously tested and evaluated for their efficacy and safety profiles.

Design, synthesis, and in vitro and in silico studies of morpholine derived thiazoles as bovine carbonic anhydrase-II inhibitors.

Carbonic anhydrase CA-II enzyme is essential for maintaining homeostasis in several processes, including respiration, lipogenesis, gluconeogenesis, calcification, bone resorption, and electrolyte balance due to its vital function within cellular processes. Herein, we screened 25 newly synthesized thiazole derivatives and assessed their inhibitory potential against the zinc-containing carbonic anhydrase CA-II enzyme. Intriguingly, derivatives of thiazole exhibited varying degrees of inhibitory action against CA-II. The distinctive attribute of these compounds is that they can attach to the CA-II binding site and block its action. Morpholine based thiazoles can be strategically modified to improve bovine CA-II inhibitor binding affinity, selectivity, and pharmacokinetics. Thiazole and morpholine moieties can boost inhibitory efficacy and selectivity over other calcium-binding proteins by interacting with target bovine CA-II binding sites. The derivatives 23-26 exhibited greater affinity when compared to the standard acetazolamide. Furthermore, kinetic study of the most potent compound 24 was performed, which exhibited concentration dependent inhibition with a K i value of 9.64 ± 0.007 μM. Molecular docking, MD simulation and QSAR analysis was also carried out to elucidate the interactions, orientation, and conformational changes of these compounds within the active site of the enzyme. Moreover, pharmacokinetic assessments showed that most of the compounds possess attributes conducive to potential drug development.

IPr*Thia - wingtip-flexible, sterically hindered, modular, N,C/S,C-chelating thiazole-donor N-heterocyclic carbene ligands.

N-Heterocyclic carbenes (NHCs) represent a pivotal class of ligands in coordination chemistry owing to their unique electronic properties. In particular, hemilabile N-heterocyclic carbenes have garnered significant attention over the past decade due to their capacity to transiently coordinate to metals and open coordination sites. However, hemilabile NHC ligands have been predominantly limited to N, O and P donors, while NHC ligands bearing versatile S-donors have been severely underdeveloped. Herein, we report wingtip-flexible, sterically hindered NHC ligands that feature N,C/S,C-chelating thiazole donors in combination with the powerful IPr* (IPr* = (2,6-bis(diphenylmethyl)-4-methylphenyl)imidazol-2-ylidene) scaffold. These ligands are prepared using a highly modular SNAr arylation of thiazole derivatives. Full structural and electronic characterization is reported. The ligands feature a high barrier to rotation around the N-thiazole axis (10 kcal mol-1). The ligands are evaluated for their steric, electron-donating and π-accepting properties as well as coordination chemistry to Ag(I), Pd(II), Rh(I) and Se. Preliminary studies on Ag, Pd and Rh catalysis are presented. The efficiency of the approach is highlighted by preparing a library of unsymmetrical imidazolium precursors. The mono-IPr* wingtip provides a highly hindered yet sterically flexible environment adjusting to metal centers, while the N-thiazolyl wingtip displays a fluxional behavior that interchanges from the hard/soft N,C to soft/soft S,C coordination. Considering the importance of hemilabile N-heterocyclic carbene ligands in metal stabilization in inorganic and organometallic chemistry, we expect that this class of ligands will be of broad interest.

Design, synthesis, molecular docking, and dynamics studies of novel thiazole-Schiff base derivatives containing a fluorene moiety and the assessment of their antimicrobial and antioxidant activity.

In this study, a series of eighteen fluorene-containing substituted thiazole derivatives were synthesized and characterized via spectral analyses. The proposed compounds were screened for their in vitro antimicrobial activity, and it was found that compound 2a displayed a significant zone of inhibition (20.3 ± 0.6 mm) against B. subtilis and compound 2b exhibited inhibitory activity (30.3 ± 0.6 mm) against a C. albicans fungal strain. Furthermore, antioxidant activity was evaluated for all analogues, where 2f exhibited a four-fold higher antioxidant capability (11.73 ± 1.22 μg mL-1) than the standard ascorbic acid. Oral bioavailability and toxicological parameters were considered, and most of the compounds satisfied Lipinski's rule of five and Veber's rule, except for one violation by a few derivatives. Molecular docking and molecular dynamics simulation were performed, providing more explicit ideas on the binding interaction and stability of compounds that exhibited wet lab activity. Average RMSD and RMSF values ranged between 0.5 Å and 2.5 Å, which indicated the stability of ligands inside the complex, yielding some engrossing insights.

Reaction of unsymmetrical α-bromo-1,3-diketones with N-substituted thioureas: regioselective access to 2-(N-arylamino)-5-acyl-4-methylthiazoles and/or rearranged 2-(N-acylimino)-3-N-aryl-4-methylthiazoles.

The present study reports some fascinating results of Hantzsch's [3 + 2] cyclic condensation of α-bromo-1,3-diketones, a tri-electrophilic synthon generated in situ by bromination of 1,3-diketones using the mild brominating reagent NBS with trinucleophilic N-substituted thioureas. Interestingly, out of a total of 20 combinations, 10 resulted in the exclusive formation of the desired 2-(N-arylamino)-5-acyl-4-methylthiazoles regioselectively, seven led to the formation of unexpected 2-(N-acylimino)-3-N-aryl-4-methylthiazoles through an interesting C-N acyl migration, and three furnished a mixture consisting of both products. The regioselectivity pattern of the two products may be attributed to a greater electrophilicity of the carbonyl carbon of the acetyl group than that of the acyl group towards both nitrogens of thiourea. The structures of the thiazole derivatives were unambiguously assigned using 1H-NMR, 13C-NMR, and rigorous heteronuclear 2D-NMR [(1H-13C) HMQC and (1H-13C) HMBC] spectroscopic techniques. The outcomes of the spectroscopic experiments were further concurred through X-ray crystallographic studies, and a plausible mechanism for acyl migration was proposed for the formation of the unexpected rearranged product.

Synthesis, in vitro acetylcholinesterase inhibitory activity and molecular modeling studies of imidazo[2,1-b]thiazole derivatives bearing thiosemicarbazide moiety

Synthesis, in vitro acetylcholinesterase inhibitory activity and molecular modeling studies of imidazo[2,1-b]thiazole derivatives bearing thiosemicarbazide moiety

A Review on Thiazole derivatives and their impact as hypoglycemic agents in drug developments

The impact of thiazole derivatives as a hypoglycemic agent has been noted for many decades. Thiazole is heterocyclic containing sulphur and nitrogen as heteroatom whereas the free pi (π) electrons can move from one bond to another freely to have aromatic properties. Due to these aromatic properties, various reactions are possible with these rings due to the various donor-acceptor position. Thiazole can regulate various physiochemical processes within the body. Due to this, it has been reported for various biological activities such as antimicrobial, antitumor, antidiabetic, antioxidant, anti-inflammatory etc. However, there are various drugs containing thiazole are rosiglitazone, pioglitazone, and troglitazone have shown their effectiveness in controlling elevated blood sugar. In this regard, the present review explains the different thiazole derivatives synthesized and their impact as hypoglycemic agents.

Synthesis of thiazole derivatives as cholinesterase inhibitors with antioxidant activity

In the present research, we synthesized two unique series of thiazole compounds having 5-bromothiophene and 3-methylthiophene (2a-2f) in their structure. After that, spectroscopic methods were used to analyze the chemical compositions of the newly synthesized molecules. Then in vitro evaluation was done to determine acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activity of the synthesized compounds using galantamine as reference standard. The compounds’ antioxidant properties were assessed using DPPH radical scavenging and ferrous ion-chelating techniques. The results of the study showed weak anticholinesterase activity against AChE and BuChE enzymes for all the final compounds. The synthesized analogs also showed significant DPPH radical scavenging activities with IC50 values in the range of 29.16 ± 0.009 to 33.09 ± 0.004 µM (for DDPH) incomparison to standard gallic acid with IC50 = 31.13 ± 0.008 µM (for DDPH). Especially, compound 2c showed the best antioxidant activity with IC50 value of 29.16 ± 0.009 µM.

Design, Synthesis and Evaluation of Pyrrol-thiazole Derivatives as AChE and BuChE Inhibitory and Antioxidant Activities

Thiazole rings are one of the most frequently used heterocyclic moieties and are found in a wide variety of biologically active chemicals. In this research project, we report the synthesis and biological activities of some new thiazole derivatives (2a-2c) as potent anti-Alzheimer’s agents. These final compounds’ structures were characterized by spectral (1H NMR, 13C NMR, and MS spectra) analyses. The highest inhibitory activity against AChE was demonstrated by compound 2c (23.73 ± 0.018 %) with chloro substitution at the meta and para positions of the phenyl ring, while the highest inhibitory activity against BuChE was produced by compound 2a (28.87± 0.003 %) with cyano substitution at the f position of the phenyl ring. Ferrous ion-chelating and DPPH techniques were also used to assess the compounds' antioxidant properties. Compound 2a showed antioxidant effect according to the DPPH method with an IC50 value of 27.18 ± 0.009 µM.

Determining Stable Structure and in Vitro Antiproliferative Properties of a Novel 3-(2-((4-Trifluoromethyl)phenyl)amino)thiazol-4-yl)-2H-chromen-2-one Molecule.

Since coumarin and thiazole derivatives are known to have antioxidant properties, a novel derivative was synthesized in this article. 3-(2-((4-(trifluoromethyl)phenyl)amino)thiazol-4-yl)-2H-chromen-2-one (ATC) was synthesized as a novel compound with high yield and characterized by Raman, FT-IR, 13 C-NMR, and 1 H-NMR spectroscopic procedures and DFT calculations. In this study, the potential in vitro antiproliferative properties of the ATC compound were evaluated on colorectal cancer (HT29) and melanoma (SK-MEL-30) cell lines. According to the results, the compound was found to be significantly active, approximately 2.6-fold, against melanoma cells compared to healthy fibroblast (L929) cells. Unlike melanoma cells, the compound did not have any adverse effects on colorectal cancer cells. Due to these findings, the compound can be harnessed as a promising antiproliferative drug candidate for preclinical studies against melanoma.

Fungal keratitis – current diagnosis and therapeutic possibilities

Keratitis and subsequent damage to the cornea resulting from infectious causes is one of the most serious problems facing ophthalmology today. One of the most common etiologies is fungal infection. Symptoms range from pain and visual deterioration, Wessely ring, inflammatory reaction in the anterior chamber or ropost. Diagnosis in addition to the classic medical and ophthalmologic examination consists of microscopic examination of scrapings, Gram examination combined with culture gives a 90% chance of detecting a fungal etiology. Good results are also observed with PCR testing, which helps speed up diagnosis. Treatment is time-consuming and has a high risk of complications. Two techniques are used to treat fungal infections of the cornea, surgical and pharmacological, such as the antifungal polyene antibiotics nystatin, natamycin, amphotericin B or thiazole derivatives like fluconazole and voriconazole. For filamentous fungi, natamycin 5% or voriconazole 1% are used at various intervals. Natamycin, despite the much poorer availability of the drug in countries such as Africa, has much better clinical results along with a lower risk of complications, as confirmed by the MUTT. A big problem also is subsequent bacterial superinfection, leading to the need for topical antibiotics. Surgical treatment is used in case of failure of pharmacotherapy, up to 4 weeks after the diagnosis of the disease, but it carries a high risk of complications. In the early stages of the disease, a new cross-linking technique can be considered, which is described as an alternative to direct antifungal or antibacterial treatment.

Synthesis of New of 4-Thiazolidinone and Thiazole Derivatives Containing Coumarin Moiety with Antimicrobial Activity.

Synthesizing hybrid molecules is one the best manner to achieve novel promising agents. Consequently, series of new thiazoles having coumarin nucleus were synthesized from 3-acetylcoumarin thiosemicarbazones. Cyclization of thiosemicarbazone derivatives with ethyl 2-chloroacetate, 1-chloropropan-2-one and 2-bromo-1-phenylethanone afforded the corresponding 4-thiazolidinones, 4-methylthiazoles and 4-phenylthiazoles, respectively. The expected antimicrobial propriety for the synthesized thiosemicarbazone and thiazole derivatives were investigated. The thiosemicarbazones and thiazolidin-4-ones showed moderate activities against G +ve and G -ve bacteria.

Synthesis of New Indole‐Based Thiazole Derivatives as Potential Antiglycation and Antiα‐Glucosidase Agents: In Vitro and In Silico Studies

AbstractDiabetes mellitus is a metabolic disease, characterized by the elevated levels of blood glucose, known as hyperglycemia. It is one of the serious health challenges, and is rapidly becoming a significant cause of morbidity, and mortality, worldwide. The persistent hyperglycemic state in diabetes mellitus leads to the formation of advanced glycation end products (AGEs), which is identified as a key factor involved in the progression of diabetes, and diabetes‐associated late complications. keeping in view the medicinal properties of indole, and thiazole, in the present study, novel indole‐based thiazoles (1–26) were synthesized, and evaluated for theirin vitro α‐glucosidase, and antiglycation activities. These indole‐based thiazoles were characterized from their spectral data. All these compounds showed moderate to excellent antiglycation activity (IC50between 642.2±0.013 to 46.93±0.003 μM) including compounds17,20,22–26which showed a significant antiglycation activity as the reference molecule, rutin (IC50=56±0.008 μM) used as standard. Further, these derivatives exhibited significantα‐glucosidase inhibition activity (P<0.001) with IC50in the range of 111.8±0.9001 and 666.5±1.0111 μM (standard drug acarbose: IC50=855.8±1.2001 μM). Binding interactions of these compounds withα‐glucosidase enzyme were studiedin silico, which showed strong correlation with the experimental data. Inhibition ofα‐glucosidase enzyme, and AGEs formation by these compounds suggest them as promising scaffolds for further studies.

Turning on Photomechanical Responses in Molecular Crystals of Anthracenyl Thiazole Derivatives by Regulating Intermolecular Interactions

Turning on Photomechanical Responses in Molecular Crystals of Anthracenyl Thiazole Derivatives by Regulating Intermolecular Interactions

Synthesis and Antioxidant Activity of Novel Thiazole and Thiazolidinone Derivatives with Phenolic Fragments

In this work, a series of thiosemicarbazones with phenol fragments were used as starting compounds for the synthesis of new effective antioxidants containing both a phenol substituent and a heterocyclic fragment: thiazole and thiazolidinone. To determine the most stable conformation of thiosemicarbazone, a potential energy scan was used, along with NOESY NMR spectroscopy data. A number of thiazole derivatives were obtained due the interaction of thiosemicarbazones with several bromoketones: bromoacetophenone, bromodimedone, and bromoacetylcoumarin. The product yields varied from 71 to 94%. Thiazolidinone derivatives were obtained through the reaction between thiosemicarbazones and chloroacetic acid or maleic anhydride with good yields of 82–95%. The antioxidant activities of all the products were determined in vitro: the radical cation scavenging activity was estimated using 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonate), while the ferric reducing capacity was determined using the ferricyanide/Prussian blue method. It was found that the antioxidant activity of most synthesized substances in both tests exceeds the activity of 4-methyl-2,6-di-tert-butylphenol, while derivatives with a fragment of 2,6-di-tert-butylphenol have the highest activity.

Synthesis and Antiproliferative Potential of Thiazole and 4-Thiazolidinone Containing Motifs as Dual Inhibitors of EGFR and BRAFV600E.

Thiazole and thiazolidinone recur in a wide range of biologically active compounds that reach different targets within the context of tumors and represent a promising starting point to access potential candidates for treating metastatic cancer. Therefore, searching for new lead compounds that show the highest anticancer potency with the fewest adverse effects is a major drug-discovery challenge. Because the thiazole ring is present in dasatinib, which is currently used in anticancer therapy, it is important to highlight the ring. In this study, cycloalkylidenehydrazinecarbothioamides (cyclopentyl, cyclohexyl, cyclooctyl, dihydronapthalenylidene, flurine-9-ylidene, and indolinonyl) reacted with 2-bromoacetophenone and diethylacetylenedicarboxylate to yield thiazole and 4-thiazolidinone derivatives. The structure of the products was confirmed by using infrared (IR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry, and single-crystal X-ray analyses. The antiproliferative activity of the newly synthesized compounds was evaluated. The most effective inhibitory compounds were further tested in vitro against both epidermal growth factor receptor (EGFR) and B-Raf proto-oncogene, serine/threonine kinase (BRAFV600E) targets. Additionally, molecular docking analysis examined how these molecules bind to the active sites of EGFR and BRAFV600E.

Two novel phosphoramide derivatives moiety as corrosion inhibitor for mild steel: Experimental and theoretical study

Two novel phosphoramide containing thiazole derivatives with the name of bis(5‐amino‐1,3,4‐thiadiazol‐2‐yl) phenylphosphonotrithioate (C1) and O, O‐diethyl (5‐((diethoxyphosphorothioyl) thio)‐1,3,4‐thiadiazol‐2yl) phosphoramidothioate (C2) as corrosion inhibition were synthesized and identified by 1H NMR, 13C NMR, 31P NMR, IR, and mass spectroscopies. The electrochemical behavior of mild steel (MS) in hydrochloric acid 1‐M (HCl) solution was perused in the absence and presence of C1 and C2. To determine corrosion inhibition of phosphoramide compounds, scanning electron microscopy (SEM), potentiodynamic polarization (PDP), and electrochemical impedance spectroscopy (EIS) were used. The EIS results show that the charge transfer resistance increases with the addition of inhibitors to the hydrochloric acid solution. The most inhibitor efficiency was 89%, which demonstrated the appropriate anti‐corrosion property of C1. EIS results show better charge transfer resistance on the surface of MS at increased inhibitor concentrations. The PDP analysis showed that C1 and C2 are mixed‐type inhibitors. The PDP examination appeared that C1 and C2 are mixed‐type inhibitors. To way better get the comes about of corrosion inhibition and structure of target compounds, the highest occupied molecular orbital (HOMO) and least unoccupied molecular orbital (LUMO) energies, hardness, dipole moment, and electrophilicity index of synthesized compounds were explored computationally using the density functional theory (DFT) strategy. The hypothetical comes about in great understanding with the exploratory information.

DalPhos/Nickel-Catalyzed C2-H Arylation of 1,3-Azoles Using a Dual-Base System.

We report a versatile method for C2 functionalization of (benz)oxazoles and (benzo)thiazoles employing a tert-butylimino-tri(pyrrolidino)phosphorane/sodium trifluoroacetate (BTPP/NaTFA) "dual-base" system in combination with an air-stable Ni(II) precatalyst containing either CyPAd-DalPhos or PhPAd-DalPhos. These catalyst systems enable access to a reaction scope that encompasses a range of challenging oxidative addition partners, including (hetero)aryl chlorides as well as pivalates, tosylates, and other related phenol derivatives. The utility of this method is demonstrated through the derivatization of an active pharmaceutical ingredient and 5 mmol synthesis of a thiazole derivative.

Emerging green synthetic routes for thiazole and its derivatives: Current perspectives.

This review article provides an overview of the green synthesis of thiazole derivatives, emphasizing sustainable and environmentally friendly methodologies. Thiazole derivatives possess significant value and find diverse applications across various fields. However, conventional synthesis methods often involve hazardous reagents and generate substantial waste, posing environmental concerns. The green synthesis of thiazole derivatives employs renewable starting materials, nontoxic catalysts, and mild reaction conditions to minimize environmental impact. Innovative techniques such as microwave irradiation, ultrasound synthesis, green solvents, a green catalyst-based approach, and mechanochemistry-mediated synthesis are employed, offering advantages in terms of scalability, cost-effectiveness, and purification simplicity. The resulting thiazole derivatives exhibit comparable or enhanced biological activities, showcasing the feasibility and practicality of green synthesis in drug discovery. This review paper underscores the importance of sustainable approaches in functional molecular synthesis and encourages further research in this domain.