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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.

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]

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]

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]

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.)

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]

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]

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]

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.)

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]

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.

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). [ABSTRACT FROM AUTHOR]

Inflammation is a protective response to a variety of infectious agents. To develop a new anti-inflammatory drug, we explored a pharmacologically important thiazole scaffold in this study. In a multi-step synthetic approach, we synthesized seven new thiazole derivatives (5a--5g). Initially, we examined the in vitro anti-inflammatory potentials of our compounds using COX-1, COX-2, and 5-LOX enzyme assays. After in vitro confirmation, the potential compounds were subjected to in vivo analgesic and anti-inflammatory studies. The hot plate method was used for analgesia, and carrageenan-induced inflammation was also assayed. Overall, all our compounds proved to be potent inhibitors of COX-2 compared to celecoxib (IC50 0.05 μM), exhibiting IC50 values in the range of 0.76--9.01 μM .Compounds 5b, 5d, and 5e were dominant and selective COX-2 inhibitors with the lowest IC50 values and selectivity index (SI) values of 42, 112, and 124, respectively. Similarly, in the COX-1 assay, our compounds were relatively less potent but still encouraging. Standard aspirin exhibited an IC50 value of 15.32 μM. In the 5-LOX results, once again, compounds 5d and 5e were dominant with IC50 values of 23.08 and 38.46 μM, respectively. Standard zileuton exhibited an IC50 value of 11.00 μM. Based on the COX/LOX and SI potencies, the compounds 5d and 5e were subjected to in vivo analgesic and anti-inflammatory studies. Compounds 5d and 5e at concentrations of 5, 10, and 20 mg/kg body weight were significant in animal models. Furthermore, we explored the potential role of compounds 5d and 5e in various phlogistic agents. Similarly, both compounds 5d and 5e were also significantly potent in the anti-nociceptive assay. The molecular docking interactions of these two compounds with the target proteins of COX and LOX further strengthened their potential for use in COX/LOX pathway inhibitions. [ABSTRACT FROM AUTHOR]

In this work, the title compound was synthesized via the Claisen–Schmidt condensation of a 2-((5-acetyl-4-methylthiazol-2-yl)amino)isoindoline-1,3-dione with 2-fluorobenzaldehyde. The structure of the synthesized compound (yield 62%) was confirmed by 1H, 13C NMR, and LC–MS spectra. According to US NCI protocols, the compound displayed a high level of antimitotic activity against tested human tumor cells, with mean GI50/TGI values of 15.72/50.68 μM. The drug-like properties of the synthesized compound were evaluated using SwissAdme, revealing satisfactory drug-like parameters, and it presents interest for the design of new synthetic agents with biological activity. [ABSTRACT FROM AUTHOR]

A new series of benzothiazole derived thiazole-based bis-benzohydrazide hybrid (1–20) analogs were synthesized. Initially, the product confirmation was identified by employing TLC and the basic skeleton of the new hybrid synthesized compounds was further confirmed through spectroscopic techniques such as 13CNMR, 1HNMR and HREI-MS. Moreover, the synthesized analogs were tested for their inhibitory activities against acetylcholinesterase and butyrylcholinesterase. In the whole series, compounds 1, 2, 3 and 6 were found with potent activity against acetylcholinesterase (AChE), and butyrylcholinesterase (BuChE). Molecular docking inveatigation of the potent compounds was performed within the active site of acetylcholinesterase and butyrylcholinesterase revealing compounds 1, 2, 3 and 6 showing promising binding orientations against both enzymes as compared to reference drug donepezil with their IC50 values 1(2.20 ± 1.40 and 3.18 ± 0.45 μM), 2 (2.89 ± 1.25 and 2.78 ± 1.49 μM), 3 (2.94 ± 1.10 and 3.07 ± 1.23 μM), 6 (5.83 ± 1.45 and 6.03 ± 3.08 μM), respectively, and reference drug (IC50 = 8.73 ± 2.68 and 9.30 ± 2.60 μM for acetylcholinesterase and butyrylchlinesterase, respectively. In addition, ADME studies were conducted to gain a deeper understanding of the functional mechanisms of a drug on a living organism. It is considered that benzothiazole derived thiazole based bis-benzohydrazide hybrid analogs (1, 2, 3, 6) might be better inhibitors of acetylcholinesterase and butyrylcholinesterase enzymes.

The current study was conducted to establish a unique synthetic route for the synthesis of varied substituted benzimidazole derived thiazole base thiazolidinone derivatives by using molecular hybridization approach. For structural interpretation of these compounds, different spectroscopic techniques such as 13CNMR, 1HNMR and spectrometric technique HREI-MS were used. These compounds were examined in vitro against AChE and BuChE to evaluate their inhibitory profile in comparison with standard drug donepezil (IC50 = 1.60 ± 0.18 µM for AChE and IC50 = 5.3 ± 0.11 µM for BuChE). All the synthesized compounds exhibit excellent to moderate activity with IC50 ranging from 1.20 ± 1.07 µM to 28.14 ± 2.38 µM for AChE and 1.70 ± 3.10 µM to 27.65 ± 0.39 µM for BuChE in contrast to donepezil. Among the members of synthesized series, analog 2 and 7 emerged as most potent analogues having IC50 = 1.64 ± 0.04 µM (AChE) and 3.19 ± 0.18 µM (BuChE) and (IC50 = 1.20 ± 1.07 µM (AChE) and 2.38 ± 1.14 µM (BuChE), respectively. The active analogues were further explored by molecular docking to evaluate their degrees of binding interaction with active site of targeted enzymes.

In order to explore new acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitors, a series of benzimidazole-fused-thiazole bearing Schiff base derivatives (1–16) were designed and synthesized and further their precise structures were elucidated using various spectroscopic tools including 1H NMR, 13C NMR and HREI-MS. All the synthesized derivatives demonstrated better acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory potential with IC50 values ranging from 0.10 ± 0.10 µM to 11.60 ± 0.40 µM (against AChE) and 0.90 ± 0.10 µM to 22.10 ± 0.60 µM (BuChE) when the results were compared with Donepezil (IC50 = 2.16 ± 0.12 µM (against AChE) & 4.5 ± 0.11 µM (against BuChE) as standard inhibitor. Specifically, the analogues 4, 5, 11, 14 and 15 were identified to be significant potent, even more active than standard drug having IC50 values of 0.80 ± 0.10, 0.50 ± 0.10, 0.60 ± 0.10, 0.10 ± 0.10, 0.10 ± 0.10 µM (against AChE) and 2.40 ± 0.10, 1.10 ± 0.10, 1.30 ± 0.10, 0.90 ± 0.10 & 0.80 ± 0.10 µM (against BuChE) respectively. The structure–activity relationship (SAR) studies were carried out for all synthesized derivatives based on substitution pattern around aryl ring. Furthermore, the molecular docking approach was developed to explore the binding mode of interactions between most active scaffolds and active sites of targeted acetylcholinesterase and butyrylcholinesterase enzymes.

Abstract Several novel approaches to target Bcl-2 proteins and apoptotic pathways have been identified in recent years for the treatment of different types of cancer including colorectal cancer. However, no effective treatments were yet developed for colorectal cancer. Twenty two novel benzoxazole and thiazole−based compounds were designed, synthesized, and evaluated as potential Bcl-2 inhibitors with anti−proliferative activity. Compounds 8g, 12e and 13d showed good to moderate anti−proliferative activity against most of the NCI 60 cell line panel with mean growth inhibition percent of 45.13, 42.29 and 29.25%, respectively. They showed the greatest cell growth inhibition percent to HCT-116 cell line with the values of 68.0, 59.11 and 43.44%, respectively. The aforementioned compounds were furtherly investigated for their effect on HCT-116 cell cycle, and they showed increase in the total apoptosis with 17, 22, and 5%, respectively. Also, the apoptotic effect of compounds 8g, 12e and 13d, were tested by their effect on altering caspase-3 expression level in HCT-116 human cell line. The three compounds showed an increase in the caspase-3 levels by 6, 8 and 3 folds, respectively in comparison with the same untreated ones. Moreover, they were evaluated for their in–vitro Bcl-2 inhibitory activity and they showed percent inhibition of 60.2, 69.2 and 50.0%, respectively. Finally, the most potent compounds 8g and 12e showed 3.864 and 2.834 folds increase in Bax level compared to the control respectively. On the other hand, Bcl-2 was down−regulated to 0.31 and 0.415 folds compared to the control. The induction of apoptosis through increase in caspase 3 expression and down−regulation of Bcl-2 is the suggested mechanism of action.

A preparative approach to thiazole-containing chromone derivatives has been developed by modifying the corresponding aldehydes with their further transformation into propenone derivatives, and finally introducing them into the Algar-Flynn-Oyamada reaction. Several methods for obtaining propenones have been analyzed, and the most effective and practically convenient one has been found. The thiazole-containing analogs of chromones obtained have a great potential as probes for a wide range of studies.

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.

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.

Considering the pivotal role of angiogenesis in solid tumor progression, we developed a novel series of quinazoline–thiazole hybrids (SA01–SA07) as antiproliferative and anti-angiogenic agents. Four out of the seven compounds displayed superior antiproliferative activity (IC50 =1.83-4.24 µM) on HepG2 cells compared to sorafenib (IC50 = 6.28 µM). The affinity towards the VEGFR2 kinase domain was assessed through in silico prediction by molecular docking, molecular dynamics studies, and MM-PBSA. The series displayed a high degree of similarity to sorafenib regarding the binding pose within the active site of VEGFR2, with a different orientation of the 4-substituted-thiazole moieties in the allosteric pocket. Molecular dynamics and MM-PBSA evaluations identified SA05 as the hybrid forming the most stable complex with VEGFR2 compared to sorafenib. The impact of the compounds on vascular cell proliferation was assessed on EA.hy926 cells. Six compounds (SA01–SA05, SA07) displayed superior anti-proliferative activity (IC50 = 0.79–5.85 µM) compared to sorafenib (IC50 = 6.62 µM). The toxicity was evaluated on BJ cells. Further studies of the anti-angiogenic effect of the most promising compounds, SA04 and SA05, through the assessment of impact on EA.hy296 motility using a wound healing assay and in ovo potential in a CAM assay compared to sorafenib, led to the confirmation of the anti-angiogenic potential. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases caused by blood coagulation system disorders are one of the leading causes of morbidity and mortality in the world. Research shows that blood clotting factors are involved in these thrombotic processes. Among them, factor Xa occupies a key position in the blood coagulation cascade. Another coagulation factor, XIa, is also a promising target because its inhibition can suppress thrombosis with a limited contribution to normal hemostasis. In this regard, the development of dual inhibitors as new generation anticoagulants is an urgent problem. Here we report the synthesis and evaluation of novel potential dual inhibitors of coagulation factors Xa and XIa. Based on the principles of molecular design, we selected a series of compounds that combine in their structure fragments of pyrrolo[3,2,1-ij]quinolin-2-one and thiazole, connected through a hydrazine linker. The production of new hybrid molecules was carried out using a two-stage method. The reaction of 5,6-dihydropyrrolo[3,2,1-ij]quinoline-1,2-diones with thiosemicarbazide gave the corresponding hydrazinocarbothioamides. The reaction of the latter with DMAD led to the target methyl 2-(4-oxo-2-(2-(2-oxo-5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1(2H)-ylidene)hydrazineyl)thiazol-5(4H)-ylidene)acetates in high yields. In vitro testing of the synthesized molecules revealed that ten of them showed high inhibition values for both the coagulation factors Xa and XIa, and the IC50 value for some compounds was also assessed. The resulting structures were also tested for their ability to inhibit thrombin. [ABSTRACT FROM AUTHOR]

Several novel approaches to target Bcl-2 proteins and apoptotic pathways have been identified in recent years for the treatment of different types of cancer including colorectal cancer. However, no effective treatments were yet developed for colorectal cancer. Twenty two novel benzoxazole and thiazole−based compounds were designed, synthesized, and evaluated as potential Bcl-2 inhibitors with anti−proliferative activity. Compounds 8g, 12e and 13d showed good to moderate anti−proliferative activity against most of the NCI 60 cell line panel with mean growth inhibition percent of 45.13, 42.29 and 29.25%, respectively. They showed the greatest cell growth inhibition percent to HCT-116 cell line with the values of 68.0, 59.11 and 43.44%, respectively. The aforementioned compounds were furtherly investigated for their effect on HCT-116 cell cycle, and they showed increase in the total apoptosis with 17, 22, and 5%, respectively. Also, the apoptotic effect of compounds 8g, 12e and 13d, were tested by their effect on altering caspase-3 expression level in HCT-116 human cell line. The three compounds showed an increase in the caspase-3 levels by 6, 8 and 3 folds, respectively in comparison with the same untreated ones. Moreover, they were evaluated for their in–vitro Bcl-2 inhibitory activity and they showed percent inhibition of 60.2, 69.2 and 50.0%, respectively. Finally, the most potent compounds 8g and 12e showed 3.864 and 2.834 folds increase in Bax level compared to the control respectively. On the other hand, Bcl-2 was down−regulated to 0.31 and 0.415 folds compared to the control. The induction of apoptosis through increase in caspase 3 expression and down−regulation of Bcl-2 is the suggested mechanism of action. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance is an increasing problem for global public health. One of the strategies to combat this issue is the synthesis of novel antimicrobials through rational drug design based on extensive structure–activity relationship studies. The thiazole nucleus is a prominent feature in the structure of many authorized antimicrobials, being clubbed with different heterocycles. The purpose of this review is to study the structure–activity relationship in antimicrobial thiazoles clubbed with various heterocycles, as reported in the literature between 2017 and 2023, in order to offer an overview of the last years in terms of antimicrobial research and provide a helpful instrument for future research in the field. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Two new series of pyrazolyl-thiazolidinone/thiazole derivatives 16a–b and 18a–j were synthesised, merging the scaffolds of celecoxib and dasatinib. Compounds 16a, 16b and 18f inhibit COX-2 with S.I. 134.6, 26.08 and 42.13 respectively (celecoxib S.I. = 24.09). Compounds 16a,16b,18c,18d and 18f inhibit MCF-7 with IC50 = 0.73–6.25 μM (dasatinib IC50 = 7.99 μM) and (doxorubicin IC50 = 3.1 μM) and inhibit A549 with IC50 = 1.64–14.3 μM (dasatinib IC50 = 11.8 μM and doxorubicin IC50 = 2.42 μM) with S.I. (F180/MCF7) of 33.15, 7.13, 18.72, 13.25 and 8.28 respectively higher than dasatinib (4.03) and doxorubicin (3.02) and S.I. (F180/A549) of 14.75, 12.96, 4.16, 7.07 and 18.88 respectively higher than that of dasatinib (S.I. = 2.72) and doxorubicin (S.I = 3.88). Derivatives 16a, 18c, 18d, 18f inhibit EGFR and HER-2 IC50 for EGFR of 0.043, 0.226, 0.388, 0.19 μM respectively and for HER-2 of 0.032, 0.144, 0.195, 0.201 μM respectively. [ABSTRACT FROM AUTHOR]

As part of our continuous efforts to discover novel c-Met inhibitors as antitumor agents, four series of thiazole/thiadiazole carboxamide-derived analogues were designed, synthesised, and evaluated for the in vitro activity against c-Met and four human cancer cell lines. After five cycles of optimisation on structure–activity relationship, compound 51am was found to be the most promising inhibitor in both biochemical and cellular assays. Moreover, 51am exhibited potency against several c-Met mutants. Mechanistically, 51am not only induced cell cycle arrest and apoptosis in MKN-45 cells but also inhibited c-Met phosphorylation in the cell and cell-free systems. It also exhibited a good pharmacokinetic profile in BALB/c mice. Furthermore, the binding mode of 51am with both c-Met and VEGFR-2 provided novel insights for the discovery of selective c-Met inhibitors. Taken together, these results indicate that 51am could be an antitumor candidate meriting further development. [ABSTRACT FROM AUTHOR]

Thiazole carboxamide derivatives were synthesized in this investigation, with a subsequent examination of their impact on GluA2 AMPA receptors. The synthesized compounds, namely MMH-1-5, were subjected to characterization using high-resolution mass spectrometry (HRMS), proton nuclear magnetic resonance (1H-NMR), and carbon-13 nuclear magnetic resonance (13C-NMR). The present work thoroughly investigates the impact of five thiazole derivatives on GluA2 AMPA receptors. This investigation examined their effects on both whole-cell currents and receptor kinetics. In addition, the cytotoxicity of the samples was assessed using the MTS test. The compound MMH-5 had the highest effect level, resulting in a notable drop in current amplitude by a factor of six. Similarly, MMH-4 and MMH-3 also caused major reductions in the current amplitude. The compounds mentioned above also influenced the rates of deactivation and desensitization. MMH-5 and MMH-4 exhibited an increase in deactivation, while MMH-5 showed reduced desensitization. Our research findings highlight the efficacy of MMH-5 as a negative allosteric modulator of GluA2 AMPA receptors, exerting substantial effects on both the magnitude and time course of receptor activity. Significantly, the compound MMH-2 demonstrated noteworthy cytotoxic effects, as evidenced by cell viability rates dropping below 6.79% for all cancer cell lines and 17.52% for the normal cell line (LX-2). Of particular interest is the pronounced cytotoxicity observed in MMH-5, suggesting its potential as a safe neuroprotective agent targeting the AMPA receptor, as indicated by cell viability percentages exceeding 85.44% across all cancer and normal cell lines. Docking simulations were performed to determine possible modes of interaction between MMH5 and the GluA2-AMPA receptor (PDB:7RZ5). The abovementioned facts and the well-documented effects of further thiazole derivatives provide a strong foundation for future research endeavors to enhance tailored treatments for neurological disorders that rely heavily on GluA2 signaling. The present study elucidates the intricate association between thiazole derivatives and GluA2 receptors, providing valuable perspectives on the prospects of enhanced and specific therapeutic interventions for diverse neurological conditions. [ABSTRACT FROM AUTHOR]

In this work, the title compound was synthesized via the Claisen–Schmidt condensation of a 2-((5-acetyl-4-methylthiazol-2-yl)amino)isoindoline-1,3-dione with 2-fluorobenzaldehyde. The structure of the synthesized compound (yield 62%) was confirmed by 1H, 13C NMR, and LC–MS spectra. According to US NCI protocols, the compound displayed a high level of antimitotic activity against tested human tumor cells, with mean GI50/TGI values of 15.72/50.68 μM. The drug-like properties of the synthesized compound were evaluated using SwissAdme, revealing satisfactory drug-like parameters, and it presents interest for the design of new synthetic agents with biological activity.

A preparative approach to the synthesis of 2-hetaryl thiazoles has been developed via the interaction of halothiazoles with stannanes according to the Stille reaction. The most effective catalysts and reaction conditions have been found. It has been determined that the formation of by-products occurs due to specific interaction of the corresponding stannanes with the carbonyl group. The by-products have been isolated and characterized. The mechanism of this interaction with the carbonyl group has not been described in literature. The 2-hetaryl thiazoles obtained have great potential as new building blocks for medicinal chemistry and as ligands due to their complexing properties.

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.

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.

Agricultural chemicals with multifunctional applications in crop protection have attracted increasing attention. Herein, two new series of thiazole and imidazo[1,2-a]pyridine derivatives containing a hydrazone substructure were designed and synthesized via a concise synthesis route. Bioassay results showed that most of the thiazole derivatives exhibited broad-spectrum fungistatic activities, which were exemplified by compounds 1c, 1e, 1g, 1h and 1j. In particular, compound 1e displayed excellent in vitro inhibitory effects with the EC50 values of 5.00, 18.24, 6.94, and 3.03 μg/mL against the fungi Botrytis cinerea, Cytospora sp, Fusarium graminearum, and Fusarium solani, respectively. Detached fruit experiments against tomato gray mold (caused by B. cinerea) in vivo revealed that the control efficiency of compound 1e at 10, 20 and 40 μg/mL for 5 days was 35.05%, 54.14% and 81.83%, respectively, which was comparable and even superior to that of the fungicide carbendazim. Additionally, the title compounds also showed remarkable larvicidal activity against M. separata and some compounds exhibited good aphicidal activity. In a word, the bioassay indicated that a certain number of title compounds had multiple biological activities. Given their excellent antifungal and larvicidal characteristics, these interesting derivatives based on the title compounds could be served as new scaffolds for the development of pesticide with multifunctional applications.

Abstract New series of biologically active triazole and pyrazole compounds containing 2, 4-disubstituted thiazole analogues (12a-l) were synthesized from p-hydroxy benzaldehyde and phenyl hydrazine in excellent yields and purity. All the synthesized compounds were unambiguously identified based on their spectral data analyses (IR, 1H-NMR, 13C-NMR spectra, and HRMS). The final derivatives were evaluated for their in vitro anti-microbial activity after thorough purification. Among all the tested compounds, the compound 12e, 12f and 12 k possess the highest growth inhibitory activity at MIC values of 4.8, 5.1 and 4.0 μg/ml respectively. The antioxidant properties of these compounds demonstrated and revealed remarkable activity compared to the standard antioxidant by using the DPPH free radical-scavenging assay. Moreover, molecular docking studies to evaluate the probable interactions with the catalytic domain of the gram-positive S. aureus topoisomerase IV enzyme may provide new insights for developing these new hybrids as potential antimicrobial agents. The binding affinities of compounds 12a-l were ranging from − 10.0 to − 11.0 kcal/mol with topoisomerase IV enzyme and with COVID-19 main protease binding affinities are ranging from − 8.2 to − 9.3 kcal/mol. These docking studies reveal that the compounds 12a-l could be the best inhibitors for the novel SARS Cov-2 virus and have more future in discovery of potent drug candidates.