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Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a broad group of compounds mediating microbial competition in nature. Azole/azoline heterocycle formation in the peptide backbone is a key step in the biosynthesis of many RiPPs. Heterocycle formation in RiPP precursors is often carried out by a scaffold protein, an ATP-dependent cyclodehydratase, and an FMN-dependent dehydrogenase. It has generally been assumed that the orchestration of these modifications is carried out by a stable complex including the scaffold, cyclodehydratase, and dehydrogenase. The antimicrobial RiPP micrococcin begins as a precursor peptide (TclE) with a 35-amino acid N-terminal leader and a 14-amino acid C-terminal core containing six Cys residues that are converted to thiazoles. The putative scaffold protein (TclI) presumably presents the TclE substrate to a cyclodehydratase (TclJ) and a dehydrogenase (TclN) to accomplish the two-step installation of the six thiazoles. In this study, we identify a minimal TclE leader region required for thiazole formation, demonstrate complex formation between TclI, TclJ, and TclN, and further define regions of these proteins required for complex formation. Our results point to a mechanism of thiazole installation in which TclI associates with the two enzymes in a mutually exclusive fashion, such that each enzyme competes for access to the peptide substrate in a dynamic equilibrium, thus ensuring complete modification of each Cys residue in the TclE core.ImportanceThiopeptides are a family of antimicrobial peptides characterized for having sulfur-containing heterocycles and for being highly post-translationally modified. Numerous thiopeptides have been identified; almost all of which inhibit protein synthesis in gram-positive bacteria. These intrinsic antimicrobial properties make thiopeptides promising candidates for the development of new antibiotics. The thiopeptide micrococcin is synthesized by the ribosome and undergoes several post-translational modifications to acquire its bioactivity. In this study, we identify key interactions within the enzymatic complex that carries out cysteine to thiazole conversion in the biosynthesis of micrococcin.

Compound 4,4′‐(1,4‐phenylenebis(thiazole‐4,2‐diyl))bis(1H‐pyrazol‐5‐amine) (5) was used in the preparation of novel pyrazolo[1,5‐a]pyrimidines incorporating a thiazole moiety (6, 7b, 8, 9, and 13–18). the reactions were described via the following reactions: acetylacetone, acetanilide, diethyl malonate, ethyl cyanoacetate, 3‐(dimethylamino)‐1‐phenylprop‐2‐en‐1‐one, 2‐((dimethylamino)methylene)‐3‐oxopentane‐nitrile, 3‐(dimethylamino)‐1‐(thiophen‐3‐yl)prop‐2‐en‐1‐one, 2‐((dimethylamino)methylene)‐5,5‐dimethylcyclo‐hexane‐1,3‐dione, dimethylformamide‐dimethylacetal, and with a mixture of p‐nitro benzaldehyde/cyclohexanone, respectively. Gram‐positive bacteria B. subtilis and B. thuringiensis, as well as Gram‐negative bacteria E. coli and P. aeruginosa, were tested for the newly synthesized compounds' in vitro antibacterial activity. Their in vitro antifungal activity against fungus strains B. Fabae and F. oxysporum was also assessed. The compounds 16–18 had the strongest activity against Gram‐positive bacteria, with MIC values = 3.125 µg/mL against B. subtilis, which is equipotent to the drug reference Chloramphenicol, and MIC values = 6.25 µg/mL against B. thuringiensis, which is equipotent to the drug reference Cephalothin. Compounds (13–18) were shown to be superimposable to CNB based on their docking results, with the exception of derivative 18. Furthermore, they demonstrated a strong binding mode with DNA gyrase B's active pocket (PDB: 1KZN) by forming several contacts with the enzyme's essential amino acids in a way that was comparable to CNB. [ABSTRACT FROM AUTHOR]

Catalytic technologies are pivotal in enhancing energy efficiency, promoting clean energy production, and reducing energy consumption in the chemical industry. The pursuit of novel catalysts for renewable energy is a long-term goal for researchers. In this work, we synthesized three two-dimensional covalent organic frameworks (COFs) featuring electron-rich carbazole-based architectures and evaluated their catalytic performance in photocatalytic organic reactions and electrocatalytic oxygen reduction reactions (ORRs). Pyrene-functionalized COF, termed as FCTD-TAPy, demonstrated excellent photocatalytic performance for amino oxidation coupling and showed a remarkable preference for substrates with electron-withdrawing groups (up to >99% Conv. and >99% Sel). Furthermore, FCTD-TAPy favored a four-electron transfer pathway during the ORR and exhibited favorable reaction kinetics (51.07 mV/dec) and a high turnover frequency (0.011 s−1). In contrast, the ORR of benzothiadiazole-based FCTD-TABT favored a two-electron transfer pathway, which exhibited a maximum double-layer capacitance of 14.26 mF cm−2, a Tafel slope of 53.01 mV/dec, and a hydrogen peroxide generation rate of 70.3 mmol g−1 h−1. This work underscores the potential of carbazole-based COFs as advanced catalytic materials and offers new insights into the design of metal-free COFs for enhanced catalytic performance. [ABSTRACT FROM AUTHOR]

Growing evidence has unveiled the pathological significance of Tau in many cancers, including the most aggressive and lethal brain tumor glioblastoma multiform (GBM). In this regard, we have recently examined the structure–activity relationship of a new series of seventeen 2-aminothiazole-fused to flavonoid hybrid compounds (TZF) on Tau-overexpressing GBM cells. Here, we evaluated the anticancer activities of the two lead compounds 2 and 9 using multi-cellular spheroids (MCSs) which represent an easy 3D human cell model to mimic GBM organization, physical constraints and drug penetration. The two compounds reduced cell evasion from spheroids up to three times, especially for Tau-expressing cells. As a first step towards a therapeutic approach, we quantified the effects of these compounds on MCS growth using two complementary protocols: single and repeated treatments. A single injection with compound 9 slowed down the growth of MCSs formed with U87 shCTRL cells by 40% at 10 µM. More interestingly, multiple treatment with compound 9 slowed the growth of U87 shCTRL spheroids by 40% at a concentration of 5 µM, supporting the increased bioavailability of compound 9 within MCSs. In conclusion, compound 9 deserves particular attention as promising candidate for specifically targeting Tau-expressing cancers such as GBM. [ABSTRACT FROM AUTHOR]

New hybrids of 4-aminothiazolo-2-quinolone-5-carbonitriles were synthesized and assessed for their antiproliferative activity against lung and colon cancer cell lines (A549 and Caco-2, respectively) in addition to normal human cells (WI-38) using MTT assay and sorafenib as reference drug. Five derivatives exhibited high potency and selectivity for A549 cancer cells. The active candidates promoted apoptosis of lung cancer cells through expression of Bax, Bcl-2, p53, EGFR, PI3K, and mTOR signaling pathway as suggested by RT-PCR data. Moreover, in vitro enzymatic inhibition assays of epidermal growth factor receptor (EGFR) and phosphoinositol 3-kinase (PI3K) were performed. A 6-methoxy-2-quinolone derivative demonstrated inhibition of EGFR comparable to that of gefitinib while a 1-ethyl-2-dihydroquinolone derivative showed significant inhibition to PI3K higher than buparlisib. [ABSTRACT FROM AUTHOR]

Diosgenin, a hydrolyzed product of phytosteroid saponin, has widely been studied for its medicinal properties. In an effort to find bioactive molecules, 25 novel thiazole‐fused diosgenin molecules have been synthesized by an efficient reaction protocol. The chemistry involves the Oppenauer oxidation followed by double bond isomerization in a one‐pot reaction, epoxidation, and the reaction of urea derivatives with the epoxyketone to synthesize the target compounds. These novel chimeric compounds were tested for their potential antimicrobial and cytotoxic properties. Antimicrobial studies against a panel of Gram‐positive and Gram‐negative led to the discovery of some of these molecules as narrow‐spectrum antimicrobial agents against Bacillus subtilis bacteria. In preliminary cytotoxicity studies, 2‐fluorophenyl derivative (10) inhibited the growth of several cell lines of the NCI‐60 cell line panels including >93 % inhibition of UO‐31 cell line. Furthermore, the hit antibacterial compounds are non‐toxic to human cancer cell lines, and the cytotoxic compound is not active against the bacterial strains, showing the selective therapeutic potential of the chimeric compounds. [ABSTRACT FROM AUTHOR]

The presented study depicts the synthesis of 11 carborane–thiazole conjugates with anticancer activity, as well as an evaluation of their biological activity as inhibitors of two enzymes: tyrosinase and 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). The overexpression of tyrosinase results in the intracellular accumulation of melanin and can be observed in melanoma. The overexpression of 11β-HSD1 results in an elevation of glucocorticoid levels and has been associated with the aggravation of metabolic disorders such as type II diabetes mellitus and obesity. Recently, as the comorbidity of melanomas and metabolic disorders is being recognized as an important issue, the search for new therapeutic options has intensified. This study demonstrates that carborane–thiazole derivatives inhibit both enzymes, exerting beneficial effects. The antiproliferative action of all newly synthesized compounds was evaluated using three cancer cell lines, namely A172 (human brain glioblastoma), B16F10 (murine melanoma) and MDA-MB-231 (human breast adenocarcinoma), as well as a healthy control cell line of HUVEC (human umbilical vein endothelial cells). The results show that 9 out of 11 newly synthesized compounds demonstrated similar antiproliferative action against the B16F10 cell line to the reference drug, and three of these compounds surpassed it. To the best of our knowledge, this study is the first to demonstrate dual inhibitory action of carborane–thiazole derivatives against both tyrosinase and 11β-HSD1. Therefore, it represents the first step towards the simultaneous treatment of melanoma and comorbid diseases such as type II diabetes mellitus. [ABSTRACT FROM AUTHOR]

A series of {1-[4-(4-chlorophenyl)-1,3-thiazol-2-yl]-1H-pyrazol-4-yl}(2-hydroxyphenyl)metha-nones 5 were synthesized from 1-[4-(4-chlorophenyl)-1,3-thiazol-2-yl]hydrazine 3 and substituted 3-formyl-chromones 4. Compounds 5 were converted into 2-[(E)-{1-[4-(4-chlorophenyl)-1,3-thiazol-2-yl]-1H-pyrazol-4-yl}(hydroxyimino)methyl]phenols 6. The synthesized compounds were characterized by spectral techniques screened for their anti-inflammatory activity. Compounds 6c and 6e showed good percent inhibition of haemolysis when compared with the standard drug celecoxib. The molecular docking study explored the essential binding mode and possible thermodynamic interactions within the binding site of COX-2 enzyme. [ABSTRACT FROM AUTHOR]

We have already proven that thiazolylketol acetates, synthetised by addition of 2-lithiothiazole to sugar lactones followed by acetylation, are efficient glycosyl donors in the presence of O-, N-, and P-nucleophiles. We describe here their first use in the C-glycosidation using trimetylsilyl cyanide as the acceptor in order to prepare, after thiazole-to-formyl unmasking and reduction, the corresponding C-ketosides. [ABSTRACT FROM AUTHOR]

In this study, we have investigated a strategy for designing some novel pyrazoline-thiazole hybrids containing azo moiety. The synthesized compounds were structurally characterized and their antibacterial activity was in vitro evaluated against gram-negative and gram-positive bacteria using the inhibition zone method. The antibacterial activity of the tested compounds was moderate to good. Compound 12c showed the best activity compared to the standard drug (Ampicillin) against S. aureus and E. coli at the concentration of 0.16 mg/mL, with the highest inhibition zone diameters of 34 mm and 37 mm, respectively. Moreover, in silico molecular docking and ADME profile studies were investigated in order to understand the binding affinity and interactions along with the ADME properties of all designed hybrids. Additionally, Density functional theory (DFT) calculations were carried out at the B3LYP/6-311G++ level of theory. The study involved an examination of the optimized geometry, molecular electrostatic potential map, and the HOMO → LUMO electronic energy gap. In accordance with the findings, the newly synthesized hybrids could be beneficial for medicine and exhibit antibacterial activity. [ABSTRACT FROM AUTHOR]

Copyright of Baghdad Science Journal is the property of Republic of Iraq Ministry of Higher Education & Scientific Research (MOHESR) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Thiazole and its derivatives play an important role in biological and non-biological fields due to several structural and electronic behaviors associated with it. Thiazole derivatives act as chemosensors because they formed metal complexes upon interacting with various heavy metal ions like Cd2+, Co2+, Cr3+, Fe3+, Ag+, Al3+, Cu2+, Pd2+, Hg2+, Ni2+, Ga3+, In3+, Sn4+, Pb2+, Zn2+ as well as other cations. These metal ions are of prime importance from the environmental point of view with high. This review article focuses on the thiazole-based colorimetric as well as fluorometric sensor for the recognition of different heavy metal cations in various specimens like agricultural, biological, and environmental. It also summarizes the binding stoichiometry, detection limit, pH, structure, and practical application of the reported thiazole-based chemosensors. Further, the sensing performances, have been discussed and compared with some reported organic sensors. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD), a neurodegenerative condition is expected to affect 152 million in 2050. The current study comprises the evaluation of thiazole based thiadiazole bearing sulfonamide derivatives to treat Alzheimer's disease. A series of compounds (1‐15) were synthesized and were studied for their anti‐Alzheimer's potential. Their IC50 values lie in the range between (19.20±0.20 nM–2.50±0.20 nM) for AChE and (19.80±0.20 nM–3.30±0.50 nM) for AChE. Among all of them, analog 2, 7, 9, and 15 were reported to possess significant activity. Among all the members of series, compound 15 having IC50=2.50±0.20 nM and 3.30±0.50 nM for AChE and BuChE, respectively, emerged as the most promising candidate due to the presence of two electronegative fluorine (F) atoms. The small and highly electronegative fluorine atoms have the ability to block the enzyme's activity by forming strong hydrogen bonds with the amino acids of the target enzymes, thereby inhibiting their function. The efficacy of these novel compounds was studied in comparison to the standard drug donepezil having IC50=5.80±0.30 nM for AChE and IC50=6.30±0.81 nM BuChE. For further assessment of inhibition potential and mode of inhibition, molecular docking study of all the potent compounds was carried out. Further, the structural identity of the synthesized compounds was confirmed using various spectroscopic techniques, including 1H‐NMR, 13C‐NMR, and High‐Resolution Electron Impact (HREI) Mass spectrometry, which provided detailed information about their molecular structure. ADME analysis of all the synthesized compounds confirmed their potential as drugs, indicating favorable pharmacokinetic properties and a promising drug profile. [ABSTRACT FROM AUTHOR]

Cancer is a fatal disease that kills thousands of people worldwide. Despite the information produced by research on cancer treatment, applications in cancer treatment are limited. Therefore, scientists' efforts to develop more effective treatment approaches continue. In the study, we aimed to determine the anticancer potential of amino thiazole compounds on human glioblastoma (U‐87 MG) and human dermal fibroblast (HDFa) cells and their inhibition effects on enzymes that cause multidrug resistance in cancer cells. 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyl‐2H‐tetrazolium bromide cell viability test was performed to understand the cytotoxic properties of thiazole derivatives. The cellular death mechanisms behind thiazole application were investigated using flow cytometry analysis. According to cell viability analysis, thiazole derivatives exhibited a greater effect on U‐87 MG than the HDFa cell line in terms of cytotoxicity. Flow cytometry showed higher apoptotic cell death in U‐87 MG cells than in the HDFa cell line. It can be concluded that thiazole compounds exert anticancer effects on U‐87 MG and HDFa as well as show apoptotic properties. Their effects on thioredoxin reductase 1 (TrxR1), glutathione S‐transferase (GST), and glutathione reductase (GR) activities, which are important in the development of chemotherapeutic methods, were also examined. From the results obtained, it was determined that the 2‐amino‐4‐(p‐tolyl)thiazole (T7) compound significantly suppressed both TrxR1 and GST activities, and the 2‐amino‐6‐methylbenzothiazole (T8) compound significantly suppressed both TrxR1 and GST activities. Compound T7 was determined to be a selective inhibitor for TrxR1 and GST targeting, and compound T8 was determined to be a selective inhibitor for TrxR1 and GR targeting glioblastoma treatment. [ABSTRACT FROM AUTHOR]

In a one-pot reaction involving 3-(2-aminothiazol-5-yl)-2H-chromen-2-one/5-(naphthalen-1-yl)thiazol-2-amines 5-6 with various substituted aldehydes and mercaptoacetic acid, we obtained the corresponding 2-(4-substituted-phenyl)-3-[5-(2-oxo-2H-chromen-3-yl)thiazol-2-yl] thiazolidin-4-ones 8(a-h) and 2-(4-substituted-phenyl)-3-[5-(naphthalen-1-yl)thiazol-2-yl] thiazolidin-4-ones 9(a-h). The antimicrobial activity of all compounds was evaluated against Pseudomonas aeruginosa (MTCC-424), Salmonella typhi (MTCC-531), Staphylococcus aureus (MTCC-737), and Candida albican (MTCC-227). Molecular docking further supported the findings, which showed that the compounds 8d and 9d had excellent antibacterial action against all tested pathogens. [ABSTRACT FROM AUTHOR]

A series of thiazolyl–catechol compounds with antioxidant and cytotoxic activities were synthesized by a Hantzsch heterocyclization, using diverse thioamides as the thiocarbonyl component and 4-chloroacetyl-catechol as haloketone. These compounds were characterized by MS, IR spectroscopy, and NMR. Their antioxidant potential was evaluated by antiradical, electron transfer, and ferrous ion chelation assays using ascorbic acid, Trolox, and EDTA-Na2 as references. The cytotoxicity of the synthesized compounds was evaluated on two different cell types, normal human foreskin fibroblasts (BJ) and human pulmonary malignant cells (A549), using gefitinib as a reference anticancer drug. The results obtained from the tests highlighted compounds 3g and 3h with significant antioxidant activities. The highest cytotoxic potency against A549 cells was exhibited by compounds 3i and 3j, while compound 3g demonstrated exceptional selectivity on malignant cells compared to gefitinib. These promising results encourage further investigation into targeted modifications on position 2 of the thiazole ring, in order to develop novel therapeutic agents. [ABSTRACT FROM AUTHOR]

A novel series of coumarin‐pyrazole‐thiazoles hybrids was designed. The methodology depended on a simple condensation reaction of 3‐(2‐oxo‐2H‐chromen‐3‐yl)‐1‐phenyl‐1H‐pyrazole‐4‐carboxaldehyde with a variety of thiazole compounds having amino or active methylene groups. In addition, another series of 1‐(thiazol‐2‐yl)‐3‐(2‐oxo‐2H‐chromen‐3‐yl)‐1H‐pyrazole‐4‐carboxaldehydes was also achieved by applying Vilsmeier‐Haack formylation on 3‐[1‐(2‐(thiazol‐2‐yl)hydrazineylidene]ethyl)‐2H‐chromen‐2‐ones. The obtained products were verified by spectral techniques such as IR, NMR, and mass spectra. To screen their abilities to inhibit cancer cell growth, these compounds were investigated against three tumor cell lines (MCF‐7, HepG2, and HCT116) using a standard method called SRB. The products 3 e, 7 b, 12 c and 14 a have considerable cytotoxic effects comparable to Doxorubicin. These products caused significant cell death by late apoptosis in all tumor cell lines. Furthermore, they preferentially induced G2 cell cycle arrest in MCF‐7 and HepG2 cells, while causing G1 cell cycle arrest in HCT116 cells. The molecular docking of these bioactive products showed good binding affinities with Cyclin‐dependent kinase 8 (CDK‐8). The ADMET‐predicted drug‐likeness properties of these bioactive compounds enable them to can used as promising anticancer agents. [ABSTRACT FROM AUTHOR]

Thiazole derivatives are a class of heterocyclic compounds that have gained significant attention in medicinal chemistry due to their diverse biological activities and therapeutic potential. This research article provides a comprehensive overview of the synthesis strategies, structural characterization, and evaluation of the functional properties of thiazole derivatives. The thiazole nucleus, a five-membered aromatic heterocycle composed of one nitrogen, one sulfur, and three carbon atoms, serves as a versatile scaffold for drug development. Thiazolopyrimidine derivatives were synthesized through one-pot condensation of substituted thiourea in alcoholic KOH, reacting with aromatic aldehyde and a-halo acid. The structure of 5,7-diphenyl-2H-thiazolo[3,2-a] pyrimidin-3(5H)-one was confirmed by FTIR and mass spectral data. [ABSTRACT FROM AUTHOR]

Macrocyclic peptides containing a thiazole or thiazoline in the backbone are considered privileged structures in both natural compounds and drug discovery, owing to their enhanced bioactivity, stability, and permeability. Here, we present the biocompatible synthesis of macrocyclic peptides from N‐terminal cysteine and C‐terminal nitrile. While the N‐terminal cysteine is incorporated during solid‐phase peptide synthesis, the C‐terminal nitrile is introduced during cleavage with aminoacetonitrile, utilizing a cleavable benzotriazole linker. This method directly yields the fully functionalized linear peptide precursor. The biocompatible cyclization reaction occurs in buffer at physiological pH and room temperature. The resulting thiazoline heterocycle remains stable in buffer but hydrolyzes under acidic conditions. While such hydrolysis enables access to macrocyclic peptides with a complete amide backbone, mild oxidation of the thiazoline leads to the stable thiazole macrocyclic peptide. While conventional oxidation strategies involve metals, we developed a protocol simply relying on alkaline salt and air. Therefore, we offer a rapid and metal‐free pathway to macrocyclic thiazole peptides, featuring a biocompatible key cyclization step. [ABSTRACT FROM AUTHOR]

Herein, new thiazole‐2‐yl‐based hydrazone derivatives were synthesized and assessed for in vitro anticancer activity against wild type A549, MCF7, DU145, and mutant H1975 cancer cell lines by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay. Among all, 4‐(4‐Chlorophenyl)‐2‐(2‐((4‐methylthiazol‐5‐yl)methylene)hydrazineyl)thiazole (4b) elicited prominent anticancer activity against wild‐type epidermal growth factor receptor (WT‐EGFR) MCF7 cancer cell line with an IC50 value of 9.57 ± 1.80 μM, whereas 4‐Methyl‐5‐((2‐(4‐(4‐nitrophenyl)thiazol‐2‐yl)hydrazineylidene)methyl)thiazole (4c) showed appreciable activity with an IC50 value of 11 ± 0.7 μM against the mutated EGFR H1975 lung cancer cells. Doxorubicin and Osimertinib were used as the standard drugs for comparison of activity. Compound (4b) significantly increased early apoptosis (30.2%) and late apoptosis (7.6%) at a 5 μM concentration in comparison with the control (early apoptosis 2.5%, late apoptosis 1.2%). The molecular docking study was performed against mutant EGFR (T790M/C797S) (PDB: 5D41) enzyme to gain information about interactions of synthesized molecules with binding pockets. Moreover, ADME study and molecular dynamic simulation studies were accomplished to gain insight into drug‐likeness and conformational stability, respectively. The findings demonstrate a promising alignment between the observed anticancer effects and computational analyses. [ABSTRACT FROM AUTHOR]

An optimal balance between excitatory and inhibitory transmission in the central nervous system provides essential neurotransmission for good functioning of the neurons. In the neurology field, a disturbed balance can lead to neurological diseases like epilepsy, Alzheimer's, and Autism. One of the critical agents mediating excitatory neurotransmission is α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors, which are concerned with synaptic plasticity, memory, and learning. An imbalance in neurotransmission finally results in excitotoxicity and neurological pathologies that should be corrected through specific compounds. Hence, the current study will prove to be an evaluation of new thiazole-carboxamide derivatives concerning AMPAR-modulating activity and extended medicinal potential. In the current project, five previously synthesized thiazole-carboxamide derivatives, i.e., TC-1 to TC-5, were used to interact with the AMPARs expressed in HEK293T cells, which overexpress different subunits of the AMPAR. Patch-clamp analysis was carried out while the effect of the drugs on AMPAR-mediated currents was followed with a particular emphasis on the kinetics of inhibition, desensitization, and deactivation. All tested TC compounds, at all subunits, showed potent inhibition of AMPAR-mediated currents, with TC-2 being the most powerful for all subunits. These compounds shifted the receptor kinetics efficiently, mainly enhancing the deactivation rates, and hence acted as a surrogate for their neuroprotective potentials. Additionally, recently published structure–activity relationship studies identified particular substituent groups as necessary for improving the pharmacologic profiles of these compounds. In this regard, thiazole-carboxamide derivatives, particularly those classified as TC-2, have become essential negative allosteric modulators of AMPAR function and potential therapeutics in neurological disturbances underlain by the dysregulation of excitatory neurotransmission. Given their therapeutic effectiveness and safety profiles, these in vivo studies need to be further validated, although computational modeling can be further developed for drug design and selectivity. This will open possibilities for new drug-like AMPAR negative allosteric modulators with applications at the clinical level toward neurology. [ABSTRACT FROM AUTHOR]

The targeted compounds in this research, resveratrol analogs 1–14, were synthesized as mixtures of isomers by the Wittig reaction using heterocyclic triphenylphosphonium salts and various benzaldehydes. The planned compounds were those possessing the trans-configuration as the biologically active trans-resveratrol. The pure isomers were obtained by repeated column chromatography in various isolated yields depending on the heteroaromatic ring. It was found that butyrylcholinesterase (BChE) was more sensitive to the heteroaromatic resveratrol analogs than acetylcholinesterase (AChE), except for 6, the methylated thiophene derivative with chlorine, which showed equal inhibition toward both enzymes. Compounds 5 and 8 achieved the highest BChE inhibition with IC50 values of 22.9 and 24.8 μM, respectively. The same as with AChE and BChE, methylated thiophene subunits of resveratrol analogs showed better enzyme inhibition than unmethylated ones. Two antioxidant spectrophotometric methods, DPPH and CUPRAC, were applied to determine the antioxidant potential of new heteroaromatic resveratrol analogs. The molecular docking of these compounds was conducted to visualize the ligand-active site complexes' structure and identify the non-covalent interactions responsible for the complex's stability, which influence the inhibitory potential. As ADME properties are crucial in developing drug product formulations, they have also been addressed in this work. The potential genotoxicity is evaluated by in silico studies for all compounds synthesized. [ABSTRACT FROM AUTHOR]

In this research, acetophenone and thiourea reacted in the presence of iodine to produce 2-amino-4- phenylthiazoles (1, 2). These compounds were then used in three different reactions to create substituted Schiffbases (3-5) by further reactions with substituted benzaldehyde. To produce thiazole, they were first reacted with sodium azide (6). After adding maleic anhydride, they interacted with thioglycolic acid to yield oxazepine (7), and lastly, thiazolidine (8). The synthesised compounds (1-8) were confirmed to have their structures clarified by CHNS and spectroscopic methods such as infrared, 1 H NMR and 13C NMR. After being produced (1-4, 6-8), these compounds were used in 2:1 ratio reaction with CoCl2.6H2O to generate cobalt complexes (9-15). These complexes' magnetic characteristics, thermal analysis (TGA), and differential thermal analysis (DTA) were investigated. Several produced compounds were also tested against the growth of four different types of bacteria. [ABSTRACT FROM AUTHOR]

The medicinal chemistry of ferrocene has gained its momentum after the discovery of biological activities of ferrocifen and ferroquine. These ferrocenyl drugs have been designed by replacing the aromatic moiety of the organic drugs, tamoxifen and chloroquine respectively, with a ferrocenyl unit. The promising biological activities of these ferrocenyl drugs have paved a path to explore the medicinal applications of several ferrocenyl conjugates. In these conjugates, the ferrocenyl moiety has played a vital role in enhancing or imparting the anticancer activity to the molecule. The ferrocenyl conjugates induce the cytotoxicity by generating reactive oxygen species and thereby damaging the DNA. In medicinal chemistry, the five membered nitrogen heterocycles (azoles) play a significant role due to their rigid ring structure and hydrogen bonding ability with the biomolecules. Several potent drug candidates with azole groups have been in use as chemotherapeutics. Considering the importance of ferrocenyl moiety and azole groups, several ferrocenyl azole conjugates have been synthesized and screened for their biological activities. Hence, in the view of a wide scope in the development of potent drugs based on ferrocenyl azole conjugates, herein we present the details of synthesis and the anticancer activities of ferrocenyl compounds bearing azole groups such as imidazole, triazoles, thiazole and isoxazoles. [ABSTRACT FROM AUTHOR]

Based on the tremendous pharmacological activities of compounds containing thiazole and carboxamide moieties, the current study aims to prepare new series of thiazole, pyrazole, pyridine, and thiophene derivatives incorporating thiazole carboxamide moiety. Construction of the target compounds was achieved via different chemical transformations and using easily accessible starting materials. The structures of the synthesized compounds were confirmed by all possible spectral and elemental analyses. Results from the in-silico studies showed different Lipophilicity (log p) and Number of Lipinsk's violations due to the presence of NH2, C≡N, OH, and C=O groups which make more electrostatic hydrogen bond interactions in compounds 17 and 20 which increase their TPSA (Å2). These results were confirmed through docking simulation with PDBID: 5I9I which showed the least binding affinity with different proteins, and optimization of these heterocyclic compounds with computational calculations and identification of their physical descriptors which showed more stabilities and directed us for biological evaluation for further studies. [ABSTRACT FROM AUTHOR]

Copyright of Duzce University Journal of Science & Technology is the property of Duzce University Journal of Science & Technology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

A series of 4-hydroxy-6-methyl-3-(1-(4-(aryl/methyl)thiazol-2-yl)-1H-pyrazol-3-yl)-2H-pyran-2-ones 3a–h have been synthesized from aryl/methyl halomethylketones and a key pyrazole intermediate 1 using a convenient one-pot synthesis method. All compounds were characterized by NMR and MS, and the structure of three of them (3a, 3b and 3f) was resolved by X-ray diffraction. These heteroatom-rich thiazole compounds were then evaluated as inhibitors of Mycobacterium tuberculosis InhA, a key enzyme involved in the type II fatty acid biosynthesis pathway of the mycobacterium. Although inhibitory activities were found to be rather weak, molecular docking studies were also been carried out to understand a possible mode of interaction with key residues in the enzyme's active site. [ABSTRACT FROM AUTHOR]

With the ultimate goal of discovering new anticancer agents, this study involved the design and synthesis of fifteen novel Schiff bases 4a,b, 5, 6a–d, 7a–e, and 8–10 which contain 3-(2-oxo-2H-chromen-3-yl)-1-(4-phenylthiazol-2-yl)-1H-pyrazole moiety. The synthetic method depended on reaction of 3-(2-oxo-2H-chromen-3-yl)-1-(4-phenylthiazol-2-yl)-1H-pyrazole-4-carboxaldehyde (3) with a series of aromatic and heteroaryl amines under ultrasound irradiation to explore the influence of aromatic and heteroaryl rings on biological activity. The chemical structures of these Schiff bases were fully elucidated using various spectral and elemental analyses. The antiproliferative activities of the Schiff bases were studied by the standard SRB method. Among the new 15 Schiff bases, derivatives 4a,b, 5, and 7b have significant cytotoxic effects against PC3, HepG2, and HCT116 cancer cell lines. These four bioactive Schiff bases significantly increased the late apoptosis of all studied tumor cells. Also, both products 4a and 4b arrested the cell cycle at the G1 phase, while both compounds 5 and 7b arrested the S and G2 phases against PC3 cells. In addition, the products 4a, 4b, 5, and 7b have promising high abilities to arrest the cell cycle at the G2 phase against HepG2 and HCT116 cells. The different substitutions on the aryl ring were the basis for the structure–activity relationship study. The molecular docking study confirmed good binding interactions of these compounds with Cyclin-dependent kinase 8 (CDK-8) receptor, while the absorption, distribution, metabolism, excretion, and toxicity (ADMET) prediction supported that these bioactive products can be promising anticancer agents. [ABSTRACT FROM AUTHOR]

Objective: The "fall armyworm" also known as Spodoptera frugiperda, is a maize pest that is native to North America. It invaded Africa in 2016 and caused serious economic damage, forcing the continent's nations to take swift action to fend off this new invading pest. It is urgently necessary to produce powerful insecticides for the efficient management of this insect pest since this parasite is a novel invading species and its resistance to insecticides has to be investigated. Methods: The synthesized thiazole-owing hydrazone derivatives are the subject of the first study on the harmful effects they cause, followed by structural relationships. Following the stated protocols, four molecules of thiazole-owing hydrazone derivatives were synthesized as pure active ingredients, and their efficacy as potential insecticides against S. frugiperda was tested. Results and Discussion: The toxicity data exhibited that compound (V) with LC50 of 13.66 and 106.25 ppm was more toxic against the 2nd and 4th larvae instars, respectively, than other synthesized compounds; the other screened compounds showed weak to strong toxicological activity against S. frugiperda. A molecular docking investigation of four synthetic compounds (III–VI) was performed against acetylcholinesterase (AChE). The molecular docking results revealed that compound (V) has the more negative docking score and best binding (docking score = –9.01 kcal/mol), followed by compounds (III), (IV), and (VI) with docking scores of –8.76, –8.53, and –7.41 kcal/mol, respectively. The protein-ligand docking postures revealed that these substances exhibited a strong affinity for the target enzyme's active site (Protein Data Bank ID: 2ACE). This work suggests that these substances may have insecticidal and AChE inhibitory properties, and it may be possible to further explore them in the process of creating pesticides that target AChE. [ABSTRACT FROM AUTHOR]

Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a broad group of compounds mediating microbial competition in nature. Azole/azoline heterocycle formation in the peptide backbone is a key step in the biosynthesis of many RiPPs. Heterocycle formation in RiPP precursors is often carried out by a scaffold protein, an ATP-dependent cyclodehydratase, and an FMN-dependent dehydrogenase. It has generally been assumed that the orchestration of these modifications is carried out by a stable complex including the scaffold, cyclodehydratase, and dehydrogenase. The antimicrobial RiPP micrococcin begins as a precursor peptide (TclE) with a 35-amino acid N-terminal leader and a 14-amino acid C-terminal core containing six Cys residues that are converted to thiazoles. The putative scaffold protein (TclI) presumably presents the TclE substrate to a cyclodehydratase (TclJ) and a dehydrogenase (TclN) to accomplish the two-step installation of the six thiazoles. In this study, we identify a minimal TclE leader region required for thiazole formation, demonstrate complex formation between TclI, TclJ, and TclN, and further define regions of these proteins required for complex formation. Our results point to a mechanism of thiazole installation in which TclI associates with the two enzymes in a mutually exclusive fashion, such that each enzyme competes for access to the peptide substrate in a dynamic equilibrium, thus ensuring complete modification of each Cys residue in the TclE core. [ABSTRACT FROM AUTHOR]

Ester 2 was produced by reacting thiourea derivative 1 with ethyl 2-chloro-3-oxobutanoate in MeOH containing piperidine. Hydrazide 3 was produced by reacting the latter ester with hydrazine hydrate in EtOH at reflux. By reacting hydrazide 3 with aromatic/heterocyclic aldehydes, twelve derivatives of hydrazide hydrazone 5a–l were produced. Spectral measurements and elemental analysis verified the molecular structure. Compounds 2, 5a, 5c, 5d, and 5f had strong effects on all the pathogenic bacterial strains according to an evaluation of the antimicrobial qualities of the synthetic compounds. With inhibitory zone diameters ranging from 16 to 20.4 mm, hydrazide hydrazone 5f exhibited the strongest activity. Additionally, the minimum inhibitory concentration (MIC) was assessed. The best outcomes were found with hydrazones 5c and 5f. For B. subtilis, the MIC of 5c was 2.5 mg/mL. For E. coli and K. pneumoniae, the MIC of 5f was 2.5 mg/mL. The molecular mechanics-generalized born surface area (MM/GBSA) was utilized to compute binding free energies via a molecular dynamics simulation analysis of the most active compounds, 5f and 5c. Moreover, computational analyses demonstrated that 5f had a substantial affinity for the active site of DNA gyrase B, suggesting that this compound could be a strong platform for new structure-based design efforts. [ABSTRACT FROM AUTHOR]

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A general and sustainable approach for the synthesis of benzimidazole-thiazole compounds via an efficient, one-pot, domino, pseudo-four-component reaction using 5-amino-2-mercaptobenzimidazole, aralkyl halides, ammonium thiocyanate, and substituted α-bromo-acetophenones in glacial acetic acid at ambient temperature to give final compounds (4a–p) in good yields in shorter time. The spectral data of synthesized compounds were evaluated by analytical and spectral techniques (IR, 1H-NMR, 13C-NMR, and ESI-HRMS). Further, some of the synthesized compounds were screened for their in-vitro antibacterial activity studies using the agar well diffusion method against Gram-positive Streptococcus pneumoniae (2451) bacteria and Gram-negative Proteous mirabilis (2081) bacteria. Based on the MIC results, it was observed that the most active compounds 4b, 4e, 4f, and 4k show promising antibacterial activity with the zone of inhibition values of 2.85 cm 2.75 cm, 3.6 cm, and 3.3 cm against both Gram-negative and positive bacteria cell lines, respectively. Further, we have also insight into the molecular simulation studies, based on the binding results, compound 4i showed stable binding interactions with streptomycin drug with the active site of the gyrase protein (PDB ID: 1KIJ). The structure–activity relationship (SAR) studies of all the title scaffolds were also established. The antibacterial activity, molecular docking studies, and molecular dynamic simulations of the title compounds suggested that these are promising antibacterial active skeletons. [ABSTRACT FROM AUTHOR]

A facile approach for the synthesis of Aloe vera mediated silver nano-particles (AgNPs) has been carried out via chemical route. The developed Aloe vera mediated AgNPs were characterized by using various techniques such as SEM, FT-IR etc. Additionally, catalytic applications of this interesting nanomaterial were utilized for the synthesis of 4-phenylthiazole- 2-amine and its derivatives. After completion of catalytic reactions, Aloe vera mediated AgNPs were easily recycled without any significant loss in catalytic activity. The robust features of the current approach involve an outstanding catalytic performance, ease of catalyst retrievability, easy work up procedure, and large substrate tolerance. Besides this, the green chemistry metrics for the products formed such as E-factor (Environment Factor), PMI (Process Mass Intensity), RME (Reaction Mass Efficiency), Atom Economy (AE) and carbon efficiency (CE) were in associated with high efficiency and selectivity which further confirms the effectiveness of this approach. This work highlights the significance of using economic and eco-friendly approach for synthesizing thiazole derivatives in good to excellent yields via Aloe vera mediated AgNPs under waste free conditions. [ABSTRACT FROM AUTHOR]

In this study, we present a series of 2-(5-chlorothiophen-2-yl)-1H-benzo-[d]-imidazol-2-yl)-6,7-dihydrobenzo-[d]-imidazo[2,1-b]thiazol-8(5H)-ones (7a–q) through a short, four-step process using readily available starting materials. The synthesis included crucial transformations such as the condensation of 1,3-cyclohexanediones with thiourea, cyclization with acetophenones, and the Vilsmeier-Haack-Arnold reaction. All the compounds were fully characterized and systematically screened for antibacterial, antifungal and antiviral activity. Among all, the compounds 7b (CC50: >1000 µM, IC50 = 4.8 µM, SI = > 63) and 7h (CC50: >1000 µM, IC50 = 5.6 µM, SI = > 54) with 3-methyl and 3-trifluoromethyl groups showed significant virus inhibitory activity against the pandemic influenza virus A/Puerto Rico/8/34 (H1N1) with high selectivity index values and favorable toxicity profiles. The compounds were also evaluated for antibacterial and antifungal activity, exhibited only moderate inhibition. Molecular docking studies have elucidated strong binding interactions with the viral target, the RNA polymerase PB1-PB2 subunits of influenza A virus. ADMET profiles highlighted encouraging drug-like properties and positioned 2-(5-chlorothiophen-2-yl)-1H-benzo-[d]-imidazol-2-yl)-6,7-dihydrobenzo-[d]-imidazo [2,1-b]thiazol-8(5H)-one as a promising candidate for further development as antiviral therapeutics. [ABSTRACT FROM AUTHOR]

The paper describes the construction of a new series of pyrimidinone-linked thiazole derivatives through bromination of the initial Biginelli reaction product followed by the Hantzsch thiazole synthesis route. Various analytical techniques, including FT-IR, 1H NMR, 13C NMR, and LCMS analysis, were employed to confirm the formation of the products. The synthesized compounds were primarily evaluated for their antibacterial activity, with a specific focus on their IC50 values. Compound 4c demonstrated the most potent efficacy, displaying MIC and MBC values that varied from 0.23 to 0.71 mg/mL and 0.46–0.95 mg/mL, respectively. The anti-inflammatory potential was also observed in analogs 4a and 4c with marked activity in the 33.2–82.9 μM concentration range. Moreover, compounds 4a, and 4c demonstrated strong antioxidant effects, as reflected by their excellent IC50 values of 38.6–43.5 μM respectively. DFT investigation showed that B. cereus was more susceptible, and E. coli was more resistant, with chloro-substituted compounds exhibiting potential reactivity. Some molecules with chloro-substituents showed promising results in density functional theory when compared to other substituents. In addition, the molecules underwent a corrosion study and demonstrated a high level of inhibition efficiency (4c) in comparison to other molecules. Further in silico studies of the synthesized thiazoles confirmed the good interactions with the target.

We have design and synthesized a new series of 1,2,4-oxadiazole incorporated thieno[2,3-d]thiazole-isoxazole-pyridine analogues (13a-j) and were confirmed by 1H NMR, 13C NMR and mass spectral data. Further, the newly synthesized compounds (13a–j) were evaluated for their preliminary anticancer activity against a panel of four human cancer cell lines such as MCF-7 (breast cancer), A549 (lung cancer), Colo-205 (colon cancer) & A2780 (ovarian cancer) by using of MTT method, the known chemotherapeutic agent as etoposide used as positive control. Most of the tested compounds were displayed good to moderate activities on all cell lines. The IC50 values showed compound ranges from 0.01 ± 0.009 µM to 8.41 ± 5.48 µM. Where positive control showed values range from 3.34 ± 0.152 µM to 0.17 ± 0.034 µM. Among them, compound 13a, 13b, 13c, 13d, 13e and 13f were showed more potent activity than etoposide. Predominantly, the compound 13a showed potent anticancer activity against MCF-7, A549, Colo-205, and A2780 cancer cell lines with IC50 values of 0.02 ± 0.007 µM, 0.01 ± 0.009 µM, 0.13 ± 0.052 µM, and 0.11 ± 0.083 µM.

In this study novel triazine-tyrosine hybrids containing thiazole or pyridine fragments were introduced as anti- Multiple Sclerosis agents. The compounds were designed according to the structure of the Sphingosine-1-phosphate receptor subtype 1 (S1P1) modulator, fingolimode. At first, docking studies was performed using crystal structures of S1P1 and Sphingosine-1-phosphate receptor subtype 3 (S1P3) to theoretically identify the selectivity of the compounds towards the S1P1 isoform. The docking results showed better binding energy (lower ΔGb) and therefore higher selectivity for S1P1 receptor than S1P3 receptor. Subsequently the designed compounds were synthesized according to proper chemical reactions and structurally analyzed with FTIR and NMR spectrophotometers. Considering the importance of the S1P1 receptor in release of lymphocytes and therefore inflammation produced in Multiple Sclerosis disease, the synthesized compounds were investigated to study lymphocyte reduction in an animal model. Compound (8e) with 2-mercaptobenzothiazole substitution at doses of 1 and 3 mg/kg showed significant reduction effect on the percentage of lymphocytes (68.80 %, 56.75 %) compared to the fingolimod (65.73 %, 20.66 %), as the positive control group.

For the treatment of NSCLC one of the promising strategies is targeted inhibition of EGFR and its mutants. In this research work, we tend to epitomize design, synthesis, in-vitro anticancer evaluation of novel indole-thiazole derivatives as novel reversible EGFR inhibitor which have trifling toxicity. The structure of the novel indole-thiazole derivatives was designed considering the standard drug EAI045. The detailed study of first generation, second generation, third generation and fourth generation EGFR inhibitors was carried out before the designing of novel indole-thiazole derivatives. The results point toward the novel indole-thiazole derivatives 7(a-n) potential as moderate to excellent anticancer compounds. The SAR studies indicated that compounds 7e, 7f, 7 h, 7 k and 7 l reveals marvellous selective inhibition of EGFRL858R/ T790M over wild type EGFR. Especially, the synthesized compounds 7e (HCC827 IC 50 = 0.23 µM, H1975 IC 50 = 0.38 µM) and 7f (HCC827 IC 50 = 0.34 µM, H1975 IC 50 = 0.42 µM) revealed excellent in vitro anticancer activity and selectivity ratio. The compounds have also shown more selectivity towards cancer cells when compared with normal cell BEAS-2B. This shows that compounds will show minimal toxicity towards normal cells. The enzyme assay results revealed that the compound 7e has an ability to inhibit reversibly EGFR L858R/T790M. The compound 7e possibly appreciably inhibit colony formation and wound healing. The compound 7e was also able to induce apoptosis in cancer cells. The docking study also proofed the aptness to inhibit EGFR L858R/T790M of the synthesized compounds. Our findings suggest that the novel indole-thiazole derivatives 7(a-n), can specifically in vitro and at cellular level, target the mutant EGFRL858R/T790M and will open the new doors for the cancer therapy against EGFR L858R/T790M mutated cancer cells.

We have already proven that thiazolylketol acetates, synthetised by addition of 2-lithiothiazole to sugar lactones followed by acetylation, are efficient glycosyl donors in the presence of O-, N-, and P-nucleophiles. We describe here their first use in the C-glycosidation using trimetylsilyl cyanide as the acceptor in order to prepare, after thiazole-to-formyl unmasking and reduction, the corresponding C-ketosides.

Abstract Various sets of thiazole, thiophene, and 2-pyridone ring structures containing a dimethylaniline component were synthesized. Substituted thiazoles 2–3 and thiophenes 5–7 were produced by reacting thiocarbamoyl compound 4 with α-halogenated reagents in different basic conditions. Also, a series of 2-pyridone derivatives 9a–f substituted with dimethylaniline was synthesized through Michael addition of malononitrile to α,β-unsaturated nitrile derivatives 8a–f. The synthesized products were structurally proven by spectroscopic methods such as IR, 1H NMR, 13C NMR, and MS data. Furthermore, the anti-cancer efficacy of the compounds was assessed using the MTT assay on two cell lines: hepatocellular carcinoma (HepG-2) and breast cancer (MDA-MB-231). The results showed the highest growth inhibition for derivatives 2, 6, 7, and 9c, which were further examined for their IC50 values. The IC50 for compound 2 showed equipotent activity (IC50 = 1.2 µM) against the HepG-2 cell line compared to Doxorubicin (IC50 = 1.1 µM). Compounds 2, 6, 7 and 9c showed very good ADME assessments for further drug administration. Moreover, the PASS theoretical prediction for the compounds showed high antimitotic and antineoplastic activities for compounds 2, 6, 7, and 9c, as well as potent inhibition activity for the insulysin enzyme (IDE). Molecular docking stimulations were performed on CDK1/CyclinB1/CKS2 (PDB ID: 4y72) and BPTI (PDB ID: 2ra3). When docked into (PDB ID: 4y72), all of the tested compounds showed considerable inhibition, and the 2-pyridone derivative 9d had the maximum binding affinity (− 8.1223 kcal/mol). While thiophene derivative 6 offered the maximum binding affinity (− 7.5094 kcal/mol) when docked into (PDB ID: 2ra3). Graphical Abstract

Inflammation is a body response against infection that activates other biological components that include various cytokines, chemokines and other biological compounds that trigger body response against pathological activities. The Arachidonic acid pathway is involved in the inflammation that is connected with lipoxygenase (LOX) and cyclooxygenase (COX) enzymes. The importance of the isoforms of LOX and COX in inflammation is well studied. At the cellular level, some of the thiazole derivatives showed potent anti-inflammatory activities especially to block LOX5 and COX2 in the inflammation. These factors include both acute and chronic inflammation in various tissues like the heart, kidney, pancreas, brain, intestine, lungs and other organs as well that lead to the damage of the organs or cells. Whether it's the infectious or non-infectious response it will further activate some of the downstream signaling pathways like lipoxygenase, cyclooxygenase, cytochrome 450, JAK-STAT, MAPK, JNK, TNF-α, Nfr2, and many more pathways that lead to activation of another chronic disease in the body. In this review, we will concentrate on thiazole molecules that serve as anti-inflammatory responses to both acute and chronic inflammation. Further, we discussed the evidence that correlates the possible connection with LOX and COX enzymes in the inflammatory pathways and their blocking ability especially through thiazole derivatives has been discussed in this present review. The current assessment is the best part of the present consequence of thiazole derivatives on anti-inflammatory studies, covering articles published from 1973 to 2023.

The present study focuses on research findings related to the development and assessment of thiadiazole-linked thiazole derivatives as promising anti-tubercular agents. We present the synthesis data of eleven new compounds (4a-4k) and confirm their structures using spectroscopic techniques. Subsequently, the compounds were screened for their anti-tuberculosis activities against M. tuberculosis H37Ra. The results demonstrated that compounds 3 and 4b exhibited minimum inhibitory concentration (MIC) of 3.90 μg/mL and 7.81 μg/mL, respectively. In-vitro, studies for few compounds exhibited high antioxidant activity against DPPH and OH radical scavengers along with minimal to no cytotoxicity against RBCs which is a promising result. Investigation of molecular docked conformations revealed different molecular interactions such as hydrogen bonds, halogen bonds, and interactions involving Pi electron cloud. The study sheds light on conserved interactions with residues like Met131, Val163, His90 and Gln161 from the tubercular MCAT enzyme. Interestingly, the synthetic chemistry reveals that the employment of tetra-n-butylammonium bromide (TBAB) plays a crucial role for N-butylation and it also expedites the reaction in tetrahydrofuran solvent.

Five derived forms of 2-oxo-2-H-chromene clubbed guanine, thiazole and imidazoline derivatives 10 (i–v), 11 (i–v), and 12 (i–v) were synthesized, characterized, and biologically tested for in vitro antimicrobial activity against two types of bacteria viz. Staphylococcus aureus (MTCC 87) and Escherichia coli (MTCC 40). The synthesized compounds demonstrated mild to moderate antibacterial activity against Escherichia coli and Staphylococcus aureus at all concentrations (100 μg/ml, 250 μg/ml, and 500 μg/ml) in comparison to standard drug ciprofloxacin. It was observed that the compounds 10i, 10v, 11i, 11v, 12i, 12ii, 12iv and 12v have noticeable activity at higher dose in comparison to standard drug. Zone of inhibition values indicated higher antimicrobial activity at 500 μg/ml against Escherichia coli and Staphylococcus aureus in case of imidazoline and thiazole clubbed coumarin derivatives in comparison to guanine derivatives. The guanine derivatives have been found to be potent at lower dose (100 μg/ml) in comparison to thiazole and imidazoline derivatives having negligible activity at 100 μg/ml. This suggests a differential efficacy profile among the synthesized compounds, with guanine derivatives showing promising activity at lower doses while thiazole and imidazole derivatives manifesting increased potency at higher concentrations. These findings underscore the potential of these novel compounds as antimicrobial agents, warranting further investigation into their mechanisms of action and therapeutic applications.

AbstractNew thymol–3,4-disubstitutedthiazole hybrids were synthesised as dual COX-2/5-LOX inhibitors. Compounds 6b, 6d, 6e, and 6f displayed in vitro inhibitory activity against COX-2 (IC50= 0.037, 0.042, 0.046, and 0.039 µM) nearly equal to celecoxib (IC50= 0.045 µM). 6b, 6d, and 6f showed SI (379, 341, and 374, respectively) higher than that of celecoxib (327). 6a–l elicited in vitro 5-LOX inhibitory activity higher than quercetin. 6a–f, 6i–l, 7a, and 7c possessed in vivo inhibition of formalin induced paw edoema higher than celecoxib. 6a, 6b, 6f, 6h–l, and 7b showed gastrointestinal safety profile as celecoxib and diclofenac sodium in the population of fasted rats. Induced fit docking and molecular dynamics simulation predicted good fitting of 6b and 6f without changing the packing and globularity of the apo protein. In conclusion, 6b and 6f achieved the target goal as multitarget inhibitors of inflammation.

Leukemia affects the body's blood‐forming tissues, especially the bone marrow and lymphatic system. Leukemia incidence varies between communities and between pathological kinds. Many treatment modalities exist for leukemia, such as chemotherapy, targeted therapy, radiation therapy, bone marrow transplantation, immunotherapy, and the engineering of immune cells to fight leukemia. Leukemia might be treated with a variety of pharmaceuticals, the most popular of which are imatinib (Gleevec), dasatinib (Sprycel), nilotinib (Tasigna), obinutuzumab (Gazyva), venetoclax (Venclexta), and so on. Thiazole is one of the scaffolds that are actively explored in leukemia. Derivatives having the thiazole nucleus have been surfacing as potent candidates in the treatment of leukemia for quite sometime now, but a consolidated report accumulating all these ventures is absent. Numerous naturally occurring substances, including flavones, alkaloids, anabolic steroids, and vitamin B1 (thiamine), include the basic thiazole molecule. Thiazole derivatives have been researched for their possible therapeutic effects in the treatment of leukemia. Thus, this review comprising reports regarding the effect of different thiazole‐based species in leukemia is a timely effort to the best of our knowledge. This review covers the chronological development of antileukemic thiazole‐based molecules, their synthesis, biological activity, and structure–activity relationships. [ABSTRACT FROM AUTHOR]

A series of novel 2,3,5‐trisubstituted thiazolidinone derivatives was designed and synthesized. Compounds were tested for their antimicrobial and antitubercular activities. Compounds 3‐(2,4‐difluorobenzyl)‐5‐[(5‐methylfuran‐2‐yl)methylidene]‐2‐(phenylimino)‐1,3‐thiazolidin‐4‐one (5 c) and 3‐(2,4‐difluorobenzyl)‐2‐((3‐fluorophenyl)imino)‐5‐((Z)‐4‐hydroxybenzylidene) thiazolidin‐4‐one (6 f) exhibited remarkable antimicrobial activity against Klebsiella pneumoniae and Escherichia coli respectively. All compounds except 3‐(2,4‐difluorobenzyl)‐5‐((3‐(4‐fluorophenyl)‐1‐phenyl‐1H‐pyrazol‐4‐yl)methylene)‐2‐(phenylimino)thiazolidin‐4‐one (5 a) and (6 f) exposed excellent antitubercular activity in comparison with the standard drugs against H37RV strain of Mycobacterium tuberculosis (ATCC No‐ 27294). In addition, molecular docking and dynamic simulations studies were performed with E. coli Mur B (EMB) (PDB ID: 2Q85), Aspergillus fumigatus sterol 14‐alpha demethylase (ASD) (PDB ID: 4UYM) and Mycobacterium tuberculosis pantothenate synthetase (MPS) (PDB ID: 3IVX) proteins against all compounds and the most potent compound (5 c) displayed higher binding proficiency. These compounds may serve as lead compounds for further optimization to achieve promising therapeutic properties. [ABSTRACT FROM AUTHOR]

In our previous work, an indolone derivative ZL170 was isolated and identified from Periplaneta americana (P. americana). Based on its characteristic structure, we used it as a lead compound to carry out structural optimization and subsequent antitumor activity evaluation. In the present study, a series of novel indolone derivatives bearing thiazole scaffold were designed and synthesized, and their antitumor activities against triple‐negative breast cancer (TNBC) were determined. The preliminary screening results showed that LJ3, LJ8, LJ23, and LJ27 display inhibition rates of over 60 % against MDA‐MB‐231cells at the concentration of 50 μM. Notably, LJ23 demonstrated an IC50 value of 32.19 μM against MDA‐MB‐231, prompting further evaluation of its inhibitory effect on TNBC cell motility. Results revealed that LJ23 effectively hindered TNBC cell migration through downregulation of the EMT process. Additionally, molecular docking was employed to predict the interaction mode between LJ23 and phosphoinositide 3‐kinase (PI3K). [ABSTRACT FROM AUTHOR]