Search

It has been reported that 4,5-dihydropyrazole and thiazole derivatives have many biological functions, especially in the aspect of anti-inflammation. According to the strategy of pharmacophore combination, we introduced thiazolinone and dihydropyrazole moiety into steroid skeleton to design and synthesize a novel series of D-ring substituted steroidal 4,5-dihydropyrazole thiazolinone derivatives, and assessed their in vitro anti-inflammatory profiles against Lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 macrophage cells. The anti-inflammatory activities assay demonstrated that compound 12e was considered as the most effective anti-inflammatory drug, which suppressed the expression of pro-inflammatory mediators including nitric oxide (NO), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), it also dose-dependently inhibited the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in LPS-induced RAW 264.7 macrophage cells. Furthermore, the results of the Western blot analysis showed a correlation between the inhibition of the Nuclear factor-kappa B (NF-κB) and Mitogen-activated protein kinases (MAPKs) signaling pathways and the suppressive effects of compound 12e on pro-inflammatory cytokines. Molecular docking studies of compound 12e into the COX-2 protein receptor (PDB ID: 5IKQ) active site was performed to rationalize their COX-2 inhibitory potency. The results were found to be in line with the biological findings as they exerted more favorable interactions compared to that of dexamethasone (DXM), explaining their remarkable COX-2 inhibitory activity. The findings revealed that these candidates could be identified as potent anti-inflammatory agents, compound 12e could be a promising drug for the treatment of inflammatory diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Extrahepatic cytochrome P450 1B1 (CYP1B1), which is highly expressed in non-small cell lung cancer, is an attractive target for cancer prevention, therapy, and overcoming drug resistance. Historically, CYP1B1 inhibition has been the primary therapeutic approach for treating CYP1B1-related malignancies, but its success has been limited. This study introduced CYP1B1 degradation as an alternative strategy to counter drug resistance and metastasis in CYP1B1-overexpressing non-small cell lung cancer A549/Taxol cells via a PROTAC strategy. Our investigation revealed that the identification of the potent CYP1B1 degrader PV2, achieving DC 50 values of 1.0 nM and inducing >90 % CYP1B1 degradation at concentrations as low as 10 nM in A549/Taxol cells. Importantly, PV2 enhanced the sensitivity of the A549/Taxol subline to Taxol, possibly due to its stronger inhibitory effects on P-gp through CYP1B1 degradation. Additionally, compared to the CYP1B1 inhibitor A1, PV2 effectively suppressed the migration and invasion of A549/Taxol cells by inhibiting the FAK/SRC and EMT pathways. These findings hold promise for a novel therapy targeting advanced CYP1B1 + non-small cell lung cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

The existing kinase inhibitors for hepatocellular carcinoma (HCC) have conferred survival benefits but are hampered by adverse effects and drug resistance, necessitating the development of novel agents targeting distinct pathways. To discover potent new anti-HCC compounds, we leveraged scaffold hopping from Sorafenib and introduced morpholine/piperidine moieties to develop ureido-substituted 4-phenylthiazole analogs with optimized physicochemical properties and binding interactions. Notably, compound 27 exhibited potent cytotoxicity against HepG2 cells (IC 50 = 0.62 ± 0.34 μM), significantly exceeding Sorafenib (IC 50 = 1.62 ± 0.27 μM). Mechanistic investigations revealed that compound 27 potently inhibited HCC cell migration and colony formation, and it induced G2/M arrest and early-stage apoptosis. Kinase profiling revealed IGF1R as a key target, which compound 27 potently inhibited (76.84% at 10 μM). Molecular modeling substantiated compound 27 's strong binding to IGF1R via multiple hydrogen bonds. Computational predictions indicate favorable drug-like properties for compound 27 . These findings provide a promising drug candidate for the treatment of HCC patients.

GSK-3β, IKK-β, and ROCK-1 kinases are implicated in the pathomechanism of Alzheimer's disease due to their involvement in the misfolding and accumulation of amyloid β (Aβ) and tau proteins, as well as inflammatory processes. Among these kinases, GSK-3β plays the most crucial role. In this study, we present compound 62 , a novel, remarkably potent, competitive GSK-3β inhibitor (IC 50 = 8 nM, K i = 2 nM) that also exhibits additional ROCK-1 inhibitory activity (IC 50 = 2.3 µM) and demonstrates anti-inflammatory and neuroprotective properties. Compound 62 effectively suppresses the production of nitric oxide (NO) and pro-inflammatory cytokines in the lipopolysaccharide-induced model of inflammation in the microglial BV-2 cell line. Furthermore, it shows neuroprotective effects in an okadaic-acid-induced tau hyperphosphorylation cell model of neurodegeneration. The compound also demonstrates the potential for further development, characterized by its chemical and metabolic stability in mouse microsomes and fair solubility.

In this study, a new series of thiazolo[4,5-b]quinoxaline derivatives 3-8 were synthesized by treating 2,3-dichloroquinoxaline with thiosemicarbazone and thiourea derivatives under reflux conditions. The chemical structure of the newly designed derivatives was conducted using spectroscopic techniques. The insecticidal bioassay of the designed derivatives was evaluated against the 2nd and 4th larvae of S. litura after five days as toxicity agents via median lethal concentration (LC 50 ) and the lethal time values (LT 50 ). The results indicated that all the tested compounds had insecticidal effects against both instar larvae of S. litura with variable values. Among them, thiazolo[4,5-b]quinoxaline derivative 3 was the most toxic, with LC 50  = 261.88 and 433.68 ppm against 2nd and 4th instar larvae, respectively. Moreover, the thiazolo[4,5-b]quinoxaline derivative 3 required the least time to kill the 50% population (LT 50 ) of 2nd larvae were 20.88, 13.2, and 15.84 hs with 625, 1250, and 2500 ppm, respectively, while for the 4th larval instar were 2.75, 2.08, and 1.76 days with concentrations of 625, 1250, and 2500 ppm, respectively. Larvae's morphological and histological studies for the most active derivative 3 were investigated. According to SEM analysis, the exterior morphology of the cuticle and head capsule was affected. In addition, there were some histological alterations in the cuticle layers and the midgut tissues. Columnar cells began breaking down, and vacuolization occurred in the peritrophic membrane. Moreover, treating 4th S litura larvae hemolymph with compound 3 showed significant changes in biochemical analysis, such as total proteins, GPT, GOT, acetylcholinesterase (AChE), and alkaline phosphatase (AlP). Finally, the toxicity prediction of the most active derivative revealed non-corrosive, non-irritant to the eye, non-respiratory toxicity, non-sensitivity to the skin, non-hepatotoxic, and don't have toxicity on minnow toxicity and T. pyriformis indicating a good toxicity profile for human., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

A series of 4-methyl-5-(3-phenylacryloyl)thiazoles based on chalcones were designed, synthesized and evaluated for their influenza neuraminidase (NA) inhibitory activity in vitro. A preliminary structure-activity relationship (SAR) analysis showed that thiazoles bearing amide had greater potency. It also showed that mono-hydroxyl group at 4-position on phenyl ring was more effective than other electron-releasing groups or electron-withdraw groups. Compounds A2 and A26 were more potent against NA with IC 50 values of 8.2 ± 0.5 μg/mL and 6.2 ± 1.4 μg/mL, respectively. Molecular docking study demonstrated that thiazoles skeleton was benefit for the NA inhibitory activity., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

To promote the development and exploitation of novel antifungal agents, a series of thiazol-2-ylbenzamide derivatives (3A-3V) and thiazole-2-ylbenzimidoyl chloride derivatives (4A-4V) were designed and selective synthesis. The bioassay results showed that most of the target compounds exhibited excellent in vitro antifungal activities against five plant pathogenic fungi (Valsa mali, Sclerotinia scleotiorum, Botrytis cinerea, Rhizoctonia solani and Trichoderma viride). The antifungal effects of compounds 3B (EC 50  = 0.72 mg/L) and 4B (EC 50  = 0.65 mg/L) against S. scleotiorum were comparable to succinate dehydrogenase inhibitors (SDHIs) thifluzamide (EC 50  = 1.08 mg/L) and boscalid (EC 50  = 0.78 mg/L). Especially, compounds 3B (EC 50  = 0.87 mg/L) and 4B (EC 50  = 1.08 mg/L) showed higher activity against R. solani than boscalid (EC 50  = 2.25 mg/L). In vivo experiments in rice leaves revealed that compounds 3B (86.8 %) and 4B (85.3 %) exhibited excellent protective activities against R. solani comparable to thifluzamide (88.5 %). Scanning electron microscopy (SEM) results exhibited that compounds 3B and 4B dramatically disrupted the typical structure and morphology of R. solani mycelium. Molecular docking demonstrated that compounds 3B and 4B had significant interactions with succinate dehydrogenase (SDH). Meanwhile, SDH inhibition assay results further proved their potential as SDHIs. In addition, acute oral toxicity tests on A. mellifera L. showed only low toxicity for compounds 3B and 4B to A. mellifera L. populations. These results suggested that these two series of compounds had merit for further investigation as potential low-risk agricultural SDHI fungicides., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Trypanosoma cruzi (T. cruzi) causes Chagas, which is a neglected tropical disease (NTD). WHO estimates that 6 to 7 million people are infected worldwide. Current treatment is done with benznidazole (BZN), which is very toxic and effective only in the acute phase of the disease. In this work, we designed, synthesized, and characterized thirteen new phenoxyhydrazine-thiazole compounds and applied molecular docking and in vitro methods to investigate cell cytotoxicity, trypanocide activity, nitric oxide (NO) production, cell death, and immunomodulation. We observed a higher predicted affinity of the compounds for the squalene synthase and 14-alpha demethylase enzymes of T. cruzi. Moreover, the compounds displayed a higher predicted affinity for human TLR2 and TLR4, were mildly toxic in vitro for most mammalian cell types tested, and LIZ531 (IC50 2.8 μM) was highly toxic for epimastigotes, LIZ311 (IC50 8.6 μM) for trypomastigotes, and LIZ331 (IC50 1.9 μM) for amastigotes. We observed that LIZ311 (IC50 2.5 μM), LIZ431 (IC50 4.1 μM) and LIZ531 (IC50 5 μM) induced 200 μg/mL of NO and JM14 induced NO production in three different concentrations tested. The compound LIZ331 induced the production of TNF and IL-6. LIZ311 induced the secretion of TNF, IFNγ, IL-2, IL-4, IL-10, and IL-17, cell death by apoptosis, decreased acidic compartment formation, and induced changes in the mitochondrial membrane potential. Taken together, LIZ311 is a promising anti-T. cruzi compound is not toxic to mammalian cells and has increased antiparasitic activity and immunomodulatory properties., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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, 1 H-NMR, 13 C-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., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Joining the global demand for the discovery of potent NSAIDs with minimized ulcerogenic effect, new pyrazole clubbed thiazole derivatives 5a-o were designed and synthesized. The new derivatives were initially evaluated for their analgesic activity. Eight compounds 5a, 5c, 5d, 5e, 5f, 5h, 5m, and 5o showed higher activity than Indomethacin (potency = 105-130 % vs. 100 %). Subsequently, they were picked for further evaluation of their anti-inflammatory activity, ulcerogenic liability as well as toxicological studies. Derivatives 5h and 5m showed a potential % edema inhibition after 3 h (79.39 % and 72.12 %, respectively), with a promising safety profile and low ulcer indices (3.80 and 3.20, respectively). The two compounds 5h and 5m were subjected to in vitro COX-1 and COX-2 inhibition assay. The candidate 5h showed nearly equipotent COX-1 inhibition (IC 50  = 38.76 nM) compared to the non-selective reference drug Indomethacin (IC 50  = 35.72 nM). Compound 5m expressed significant inhibitory activities and a higher COX-2 selectivity index (IC 50  = 87.74 nM, SI = 2.05) in comparison with Indomethacin (SI = 0.52), with less selectivity than Celecoxib (SI = 8.31). Simulation docking studies were carried out to gain insights into the binding interaction of compounds 5h and 5m in the vicinity of COX-1 and COX-2 enzymes that illustrated the importance of pyrazole clubbed thiazole core in hydrogen bonding interactions. The thiazole motif of compounds 5h and 5m exhibited a well orientation toward COX-1 Arg120 key residue by hydrogen bonding interactions. Compound 5h revealed an additional arene-cation interaction with Arg120 that could rationalize its superior COX-1 inhibitory activity. Compounds 5h and 5m overlaid the co-crystallized ligand Celecoxib I differently in the active site of COX-2. Compound 5m showed an enhanced accommodation with binding energy of - 6.13 vs. - 1.70 kcal/mol of compounds 5h. The naphthalene ring of compound 5m adopted the Celecoxib I benzene sulfonamide region that is stabilized by hydrogen-arene interactions with the hydrophobic sidechains of the key residues Ser339 and Phe504. Further, the core structure of compound 5m, pyrazole clubbed thiazole, revealed deeper hydrophobic interactions with Ala513, Leu517 and Val509 residues. Finally, a sensitive and accurate UPLC-MS/MS method was developed for the simultaneous estimation of some selected promising pyrazole derivatives in rat plasma. Accordingly, compounds 5h and 5m were suggested to be promising potent analgesic and anti-inflammatory agents with improved safety profiles and a novel COX isozyme modulation activity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Tuberculosis remains a global health threat, with increasing infection rates and mortality despite existing anti-TB drugs. The present work focuses on the research findings regarding the development and evaluation of thiadiazole-linked thiazole derivatives as potential anti-tuberculosis agents. We present the synthesis data and confirm the compound structures using spectroscopic techniques. The current study reports twelve thiazole-thiadiazole compounds (5 a-5 l) for their anti-tuberculosis and related bioactivities. This paper emphasizes compounds 5 g, 5 i, and 5 l, which exhibited promising MIC values, leading to further in silico and interaction analysis. Pharmacophore mapping data included in the present analysis identified tubercular ThyX as potential drug targets. The compounds were evaluated for anti-tubercular activity using standard methods, revealing significant MIC values, particularly compound 5 l, with the best MIC value of 7.1285 μg/ml. Compounds 5 g and 5 i also demonstrated moderate to good MIC values against M. tuberculosis (H37Ra). Structural inspection of the docked poses revealed interactions such as hydrogen bonds, halogen bonds, and interactions containing Pi electron cloud, shedding light on conserved interactions with residues like Arg 95, Cys 43, His 69, and Arg 87 from the tubercular ThyX enzyme., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Diabetes is a leading cause of kidney failure, blindness, heart attacks and lower limb amputation. Prevalence of diabetes is rising globally. α-glucosidase is validated target for controlling hyperglycemia because of its role in catalysing hydrolysis of carbohydrates to glucose in GIT. In an attempt to find novel safe and effective α-glucosidase inhibitors, coumarin linked thiazole was identified as potential scaffold on the basis of its interactions with the active site of α-glucosidase studied in silico. A series of coumarin linked thiazole derivatives were synthesized and analyzed for α-glucosidase inhibitory potential in an in-vitro assay. The synthesized molecules showed potent inhibition of α-glucosidase with IC50 values ranging from 0.14 to 9.38 μM. The most potent compound 2-[(4-bromophenyl) amino)-N-(4- (2-oxo-2H-chromen-3-yl) thiazol-2-yl] acetamide was further docked with α-glucosidase and molecular dynamics studies were carried out for 100 ns which suggested the stability of protein and ligand in the protein active site over the simulation period and role of hydrophobic interactions slightly more than the electrostatic/polar interactions in ligand- receptor stability. In summary, our results demonstrate efficacy of coumarin-linked thiazole as potential leads for further optimization and development., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Inflammation, an important biological protective response to tissue damage or microbial invasion, is considered to be an alarming signal for the progress of varied biological complications. Based on the previous reports in the literature that proved the noticeable efficacy of pyrazole and thiazole scaffold as well as nitrogen heterocyclic based compounds against acute and chronic inflammatory disease, a new set of novel D-ring substituted steroidal 4,5-dihydropyrazole thiazole derivatives were synthesized and evaluated their anti-inflammatory activities in vitro. Preliminary structure-activity relationship (SAR) analysis was conducted by their inhibitory activities against nitric oxide (NO) release in lipopolysaccharide (LPS)-induced RAW 264.7 cells, and the optimal compound 12b [3β-hydroxy-pregn-5-en-17β-yl-5'- (o- chlorophenyl)- 1'-(4''- phenyl -[1'', 3'']- thiazol-2''- yl) - 4',5'-dihydro - 1'H-pyrazol - 3'- yl] exhibited more potent anti-inflammatory activity than the positive control treatment methylprednisolone (MPS), with an IC 50 value of 2.59 μM on NO production and low cytotoxicity against RAW 264.7 cells. In further mechanism study, our results showed that compound 12b significantly suppressed the production of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and inhibited the expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) through blocking NF-κB p65 nuclear translocation and phosphorylation of IκBα. Compound 12b also attenuated LPS-induced activation of c-Jun amino-terminal kinase (JNK) and p38 phosphorylation in RAW 264.7 cells. Molecular docking study revealed the strong binding affinity of compound 12b to the active site of the COX-2 proteins, which confirmed that compound 12b acted as an anti-inflammatory mediator. These results indicate that steroidal derivatives bearing 4,5-dihydropyrazole thiazole structure might be considered for further research and scaffold optimization in designing anti-inflammatory drugs and compound 12b might be a promising therapeutic anti-inflammatory drug candidate., Competing Interests: Declaration of Competing Interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of the manuscript entitled., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The main challenge in the development of agrochemicals is the lack of new leads and/or targets. It is critical to discover new molecular targets and their corresponding ligands. YZK-C22 , which contains a 1,2,3-thiadiazol-[1,2,4]triazolo[3,4- b ][1,3,4]thiadiazole skeleton, is a fungicide lead compound with broad-spectrum fungicidal activity. Previous studies suggested that the [1,2,4]triazolo[3,4- b ][1,3,4]thiadiazole scaffold exhibited good antifungal activity. Inspired by this, a series of pyrrolo[2,3- d ]thiazole derivatives were designed and synthesized through a bioisosteric strategy. Compounds C1 , C9 , and C20 were found to be more active against Rhizoctonia solani than the positive control YZK-C22. More than half of the target compounds provided favorable activity against Botrytis cinerea , where the EC 50 values of compounds C4 , C6 , C8 , C10 , and C20 varied from 1.17 to 1.77 μg/mL. Surface plasmon resonance and molecular docking suggested that in vitro potent compounds C9 and C20 have a new mode of action instead of acting as pyruvate kinase inhibitors. Transcriptome analysis revealed that compound C20 can impact the tryptophan metabolic pathway, cutin, suberin, and wax biosynthesis of B. cinerea . Overall, pyrrolo[2,3- d ]thiazole is discovered as a new fungicidal lead structure with a potential new mode of action for further exploration.

Photosensitizers cause oxidative damages in various biological systems under light. In this study, the method for analyzing photosensitizing activity of various dietary and medicinal sources was developed using 1-(4,5-dimethylthiazol-2-yl)-3,5-diphenylformazan (thiazolyl blue formazan; MTT-F) as a probe. Significant and quantitative decolorization of MTT-F was observed in the presence of photosensitizers used in this study under light but not under dark conditions. The decolorization of MTT-F occurred irradiation time-, light intensity-, and photosensitizer concentration-dependently. The decolorized MTT-F was reversibly reduced by living cells; the LC-MS/MS results indicated the formation of oxidized products with -1 m / z of base peak from MTT-F, suggesting that MTT-F decolorized by photosensitizers was its corresponding tetrazolium. The present results indicate that MTT-F is a reliable probe for the quantitative analysis of photosensitizing activities, and the MTT-F-based method can be an useful tool for screening and evaluating photosensitizing properties of various compounds used in many industrial purposes.

Combined in silico strategy for molecular mechanisms exploration of a series 3H-thiazolo[4,5-b]pyridin-2-ones exhibiting strong anti-exudative action through QSAR analysis, molecular docking and pharmacophore modelling is reported. GA-ML technique was used for QSAR models generation with 2D autocorrelation descriptors. One- and two-parameter regressions revealed that certain structural patterns or heteroatoms contribute mutually to the anti-exudative activity potentiation. Possible action mechanisms were discovered through flexible docking simulations with cyclooxygenase pathway enzymes (COX-1, COX-2, mPGES-1). Docking results indicated the possibility of stable complexes formation with the effective docking scores and proper orientation of ligands within the enzymes active sites. Pharmacophore modelling was carried out using protein-ligand interaction fingerprints methodology. Two- and three-centre 3D pharmacophore queries were constructed. Their analysis indicated the functionality of bicyclic thiazolopyridine scaffold proved by the steric placement of heteroatoms in the corresponding pharmacophore centres.

A thiazole-based probe, N '-((2-aminothiazol-5-yl)methylene)benzohydrazide ( TBH ), has been efficiently synthesized and characterized for the selective and sensitive detection of the neurotransmitter epinephrine (EP). The sensing strategy is based on the use of TBH for sequential colorimetric sensing of Ag + and EP via in situ formation of Ag nanoparticles (Ag NPs) from the TBH -Ag + complex. The generated Ag NPs lead to a bathochromic shift in absorption maximum and a change in color of the solution from light brown to reddish brown. TBH -Ag + shows remarkable selectivity toward EP versus other drugs, common cations, anions, and some biomolecules. Moreover, TBH -Ag + has a low detection limit for EP at 1.2 nM. The coordination of TBH -Ag + has been proposed based on Job's plot, Fourier transform infrared spectroscopy (FT-IR), high-resolution mass spectrometry (HRMS), 1 H NMR titration, X-ray photoelectron spectroscopy (XPS), energy-dispersive X-ray analysis (EDAX), and density functional theory (DFT) studies. The composition and morphology of the generated Ag NPs have been analyzed by XPS, scanning electron microscopy (SEM), transmission electron microscopy (TEM), and dynamic light scattering (DLS). The proposed sensing mechanism for EP has been supported by XPS of Ag after the reaction. Further, the sensitivity of TBH -Ag + toward EP in brain tissues of an Alzheimer's disease model of mouse has been evaluated. A thorough comparison was done for evaluation of the proposed method.

Indole phytoalexins, found in economically significant Cruciferae family plants, are synthesized in response to pathogen attacks or stress, serving as crucial components of plant defense mechanisms against bacterial and fungal infections. Furthermore, recent research indicates that these compounds hold promise for improving human health, particularly in terms of potential anticancer effects that have been observed in various studies. Since our last comprehensive overview in 2016 focusing on the antiproliferative effects of these substances, brassinin and camalexin have been the most extensively studied. This review analyses the multifaceted pharmacological effects of brassinin and camalexin, highlighting their anticancer potential. In this article, we also provide an overview of the antiproliferative activity of new synthetic analogs of indole phytoalexins, which were synthesized and tested at our university with the aim of enhancing efficacy compared to the parent compound.

The β-adrenergic drug Mirabegron, a drug initially used for the treatment of an overactive bladder, has new potential indications and is hydrolyzed by butyrylcholinesterase (BChE). This compound is one of the only arylacylamide substrates to be catabolized by BChE. A steady-state kinetic analysis at 25 °C and pH 7.0 showed that the enzyme behavior is Michaelian with this substrate and displays a long pre-steady-state phase characterized by a burst. The induction time, τ , increased with substrate concentration ( τ ≈ 18 min at maximum velocity). The kinetic behavior was interpreted in terms of hysteretic behavior, resulting from a slow equilibrium between two enzyme active forms, E and E'. The pre-steady-state phase with the highest activity corresponds to action of the E form, and the steady state corresponds to action of the E' form. The catalytic parameters were determined as k cat = 7.3 min -1 and K m = 23.5 μM for the initial (burst) form E, and k cat = 1.6 min -1 and K m = 3.9 μM for the final form E'. Thus, the higher affinity of E' for Mirabegron triggers the slow enzyme state equilibrium toward a slow steady state. Despite the complexity of the reaction mechanism of Mirabegron with BChE, slow BChE-catalyzed degradation of Mirabegron in blood should have no impact on the pharmacological activities of this drug.

A dual-targeting approach is predicted to yield better cancer therapy outcomes. Consequently, a series of coumarin-based thiazoles ( 5a - h , 6 , and 7a - e ) were designed and constructed as potential carbonic anhydrase (CA) and VEGFR-2 suppressors. The inhibitory actions of the target compounds were assessed against CA isoforms IX and VEGFR-2. The assay results showed that coumarin-based thiazoles 5a , 5d , and 5e can effectively inhibit both targets. 5a , 5d , and 5e cytotoxic effects were tested on pancreatic, breast, and prostate cancer cells (PANC1, MCF7, and PC3). Further mechanistic investigation disclosed the ability of 5e to interrupt the PANC1 cell progression in the S stage by triggering the apoptotic cascade, as seen by increased levels of caspases 3, 9, and BAX, alongside the Bcl-2 decline. Moreover, the in vivo efficacy of compound 5e as an antitumor agent was evaluated. Also, molecular docking and dynamics displayed distinctive interactions between 5e and CA IX and VEGFR-2 binding pockets.

Ribonuclease H (RNase H) was identified as an important target for HIV therapy. Currently, no RNase H inhibitors have reached clinical status. Herein, a series of novel thiazolone[3,2- a ]pyrimidine-containing RNase H inhibitors were developed, based on the hit compound 10i , identified from screening our in-house compound library. Some of these derivatives exhibited low micromolar inhibitory activity. Among them, compound 12b was identified as the most potent inhibitor of RNase H (IC 50 = 2.98 μM). The experiment of magnesium ion coordination was performed to verify that this ligand could coordinate with magnesium ions, indicating its binding ability to the catalytic site of RNase H. Docking studies revealed the main interactions of this ligand with RNase H. A quantitative structure activity relationship (QSAR) was also conducted to disclose several predictive mathematic models. A molecular dynamics simulation was also conducted to determine the stability of the complex. Taken together, thiazolone[3,2- a ]pyrimidine can be regarded as a potential scaffold for the further development of RNase H inhibitors.

In this study, in order to further search anti-inflammatory drugs with high efficiency and low toxicity, this study took the ring of indoles and imidazole [2,1-b] thiazole as the main skeleton. A total of nine new N-1-substituted derivatives of indole-2-carboxyamide-phenylimidazoles [2,1-b] thiazole (13-20) was synthesized through the processes of cyclization, amino reduction, ester hydrolysis, dehydration condensation and acyl chloride substitution. These derivatives were then tested for their ability to reduce inflammation in RAW 264.7 macrophages. There was a significant majority of these compounds that effectively suppressed the production of NO, IL-6 and TNF-α in RAW 264.7 cells that were stimulated by LPS. One of these compounds, compound 19, was shown to be capable of efficiently lowering the levels of LPS-induced over expression of a number of inflammatory mediators. The inhibition rates for compound 19 were 54.66%, 68.82% and 43.74%, respectively. Additionally, an initial structure-activity relationship evaluation was carried out. The findings indicate that the incorporation of substituted benzyl moieties at the same position provided N-benzylation compounds with a positive anti-inflammatory effect. The electrophilicity of the substituent on the benzyl group had the potential to have an effect on the anti-inflammatory effect, which is something that calls for further investigation.

Personal care products (PCPs) are integral components of daily human existence, including a large number of chemicals intentionally added for functional attributes (e.g., preservatives and fragrances) or unintentionally present, such as plasticizers. This investigation aimed to optimize the methodology for target and suspect screening via liquid chromatography-high-resolution mass spectrometry, focusing on nine prevalent organic additives (comprising bisphenols A, F, and S, methyl, ethyl, propyl, and butylparaben, 5-chloro-2-methyl-4-isothiazolin-3-one, and 4-hydroxybenzoic acid). A total of 50 high-selling PCPs were purchased from the local online market as samples. In detail, PCP samples were classified into body washes, shampoos, hair conditioners, facial cleansers, body lotions, and moisture creams. For calibration, the quality assurance and quality control results demonstrated a coefficient of determination ( R 2 ) surpassing 0.999, with detection and quantification limits ranging from 2.5 to 100.0 ng/g. For recovery experiments, replicate recoveries ( n = 5) ranged from 61 to 134%. In purchased PCP samples, five of the nine target compounds were detected via a target screening. Methylparaben exhibited the highest concentration (7860 mg/kg) in a facial cleanser, which is known as an endocrine-disrupting chemical. A total of 248 suspects of organic additives were screened in PCPs, leading to a tentative identification of 9. Confirmation (confidence level 1) via reference standards was achieved for three suspects, while six were tentatively identified with a confidence level of 2. This two-step extraction methodology utilizing methyl tert -butyl ether and isopropyl alcohol enabled simultaneous analysis of diverse chemical groups with distinct properties.

This study aims to explore the essential functional requirements associated with controlling the proliferation of microbes in the domain of textiles used in public health areas. Herein, three antimicrobial agents, specifically iodopropylbutylcarbamate (IPBC), 1-hydroxypyridine-2-thioketone zinc (ZPT), and 2-octyl-3-isothiazolinone (OIT), were chosen for fabric finishing based on their notable effectiveness, minimal toxicity, cost-efficiency, and chemical stability. Utilizing Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) as representative bacterial strains, the Minimum Inhibitory Concentration (MIC50) of individual and combined antimicrobial agents was measured, and their antimicrobial effectiveness was rigorously evaluated. Concurrently, the antimicrobial effectiveness, whiteness, and mechanical durability of the fabric following antimicrobial treatment were thoroughly examined. The results demonstrate that some combinations of the three antimicrobial agents elicit additive effects on both S. aureus and E. coli. Notably, at an equivalent ratio of IPBC, ZPT, and OIT and a total concentration of 0.2 wt. %, the inhibition rates against both bacterial strains surpass 99%. Upon application to nylon fabric, the treated material demonstrates significant antimicrobial properties, with minimal reduction observed in the whiteness and tensile strength of the treated nylon. This study provides practicable strategies relevant to the production of textiles endowed with antimicrobial properties., (2024 Published under an exclusive license by the AVS.)

The literature reports that thiazole and isatin nuclei present a range of biological activities, with an emphasis on anticancer activity. Therefore, our proposal was to make a series of compounds using the molecular hybridization strategy, which has been used by our research group, producing hybrid molecules containing the thiazole and isatin nuclei. After structural planning and synthesis, the compounds were characterized and evaluated in vitro against breast cancer cell lines (T-47D, MCF-7 and MDA-MB-231) and against normal cells (PBMC). The activity profile on membrane proteins involved in chemoresistance and tumorigenic signaling proteins was also evaluated. Among the compounds tested, the compounds 4c and 4a stood out with IC 50 values of 1.23 and 1.39 μM, respectively, against the MDA-MB-231 cell line. Both compounds exhibited IC 50 values of 0.45 μM for the MCF-7 cell line. Compounds 4a and 4c significantly decreased P-gp mRNA expression levels in MCF-7, 4 and 2 folds respectively. Regarding the impact on tumorigenic signaling proteins, compound 4a inhibited Akt2 in MDA-MB-231 and compound 4c inhibited the mRNA expression of VIM in MCF-7., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Imidazoles and phenylthiazoles are an important class of heterocycles that demonstrate a wide range of biological activities against various types of cancers, diabetes mellitus and pathogenic microorganisms. The heterocyclic structure having oxothiazolidine moiety is an important scaffold present in various drugs, with potential for enzyme inhibition. In an effort to discover new heterocyclic compounds, we synthesized 26 new 4,5-diphenyl-1H-imidazole, phenylthiazole, and oxothiazolidine heterocyclic analogues that demonstrated potent α-glucosidase inhibition and anticancer activities. Majority of the compounds noncompetitively inhibited α-glucosidase except for two that exhibited competitive inhibition of the enzyme. Docking results suggested that the noncompetitive inhibitors bind to an apparent allosteric site on the enzyme located in the vicinity of the active site. Additionally, the analogues also exhibited significant activity against various types of cancers including non-small lung cancer. Since tubulin protein plays an important role in the pathogenesis of non-small lung cancer, molecular docking with one of the target compounds provided important clues to its binding mode. The current work on imidazoles and phenylthiazole derivatives bears importance for designing of new antidiabetic and anticancer drugs., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

The coumarin is one of the most promising classes of non-classical carbonic anhydrase (CA, EC 4.2.1.1) inhibitors. In continuation of our ongoing work on search of coumarin based selective carbonic anhydrase inhibitors, a new series of 6-aminocoumarin based 16 novel analogues of coumarin incorporating thiazole (4a-p) have been synthesized and studied for their hCA inhibitory activity against a panel of human carbonic anhydrases (hCAs). Most of these newly synthesized compounds exhibited interesting inhibition constants in the nanomolar range. Among the tested compounds, the compounds 4f having 4-methoxy substitution exhibited activity at 90.9 nM against hCA XII isoform. It is noteworthy to see that all compounds were specifically and selectively active against isoforms hCA IX and hCA XII, with K i under 1000 nM range. It is anticipated that these newly synthesized coumarin-thiazole hybrids (4a-p) may emerge as potential leads candidates against hCA IX and hCA XII as selective inhibitors compared to hCA I and hCA II., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Enhancing α7 nAChR function serves as a therapeutic strategy for cognitive disorders. Here, we report the synthesis and evaluation of 2-arylamino-thiazole-5-carboxylic acid amide derivatives 6 - 9 that as positive allosteric modulators (PAMs) activate human α7 nAChR current expressed in Xenopus ooctyes. Among the 4-amino derivatives, a representative atypical type I PAM 6p exhibits potent activation of α7 current with an EC 50 of 1.3 μM and the maximum activation effect on the current over 48-fold in the presence of acetylcholine (100 μM). The structure-activity relationship (SAR) analysis reveals that the 4-amino group is crucial for the allosteric activation of α7 currents by compound 6p as the substitution of 4-methyl group results in its conversion to compound 7b (EC 50 = 2.1 μM; max effect: 58-fold) characterized as a typical type I PAM. Furthermore, both 6p and 7b are able to rescue auditory gating deficits in mouse schizophrenia-like model of acoustic startle prepulse inhibition.

A one-pot microwave assisted telescopic approach is reported for the chemo-selective synthesis of substituted 1,3-thiazetidines using readily available 2-aminopyridines/pyrazines/pyrimidine, substituted isothiocyanates and 1,2-dihalomethanes. The procedure involves thiourea formation from 2-aminopyridines/pyrazines/pyrimidine with the substituted isothiocyanates followed by a base catalysed nucleophilic attack of the CS bond on the 1,2-dihalomethane. Subsequently, a cyclization reaction occurs to yield substituted 1,3-thiazetidines. These four membered strained ring systems are reported to possess broad substrate scope with high functional group tolerance. The above synthetic sequence for the formation of four membered heterocycles is proven to be a modular and straightforward approach. Further the mechanistic pathway for the formation of 1,3-thiazetidines was supported by computational evaluations and X-ray crystallography analyses. The relevance of these thiazetidines in biological applications is evaluated by studying their ability to bind bio-macromolecules like proteins and nucleic acids.

The current study details a sequence of sequential reactions for synthesizing bis-indole-based triazine bearing thiazole derivatives. Several steps were involved in the synthesis of bis-indole-based triazine bearing thiazole derivative. The synthetic reactions were monitored via thin-layer chromatography (TLC). Synthesized compounds were characterized using various spectroscopic techniques, including 1 H NMR, 13 C NMR, and HR-EIMS. The inhibitory activity against urease enzyme of these synthesized compounds was compared with that of thiourea, a standard drug (IC 50  = 9.30 ± 0.20 µM). A range of inhibitory potencies were observed for the synthesized compounds, ranging from moderate to excellent, as follows (IC 50  = 5.10 ± 0.40 µM to 29.80 ± 0.20 µM). Analyzing the structure-activity relationship (SAR) provided insight into the results, showing that different substituents had different effects on aromatic rings. Several compounds displayed outstanding inhibitory properties (among those tested were 1 , 2 , 4 , 5 , and 6 with IC 50  = 6.30 ± 0.80, 5.10 ± 0.40, 5.90 ± 0.50, 8.20 ± 0.10, 8.90 ± 0.60 µM, respectively). Anti-urease evaluation of all the synthesized derivatives was conducted in which the selected compounds have shown remarkable potency compared with the standard drug thiourea (IC 50  = 9.30 ± 0.20 µM). Molecular docking analysis was carried out for investigating the better binding sites and distance of the derivatives. Moreover, the drug-like properties were explored by the ADME attributes of the synthesized analogs., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

The emergence of multidrug-resistant (MDR) microorganisms combined with the ever-draining antibiotic pipeline poses a disturbing and immensely growing public health challenge that requires a multidisciplinary approach and the application of novel therapies aimed at unconventional targets and/or applying innovative drug formulations. Hence, bacterial iron acquisition systems and bacterial Fe 2+/3+ -containing enzymes have been identified as a plausible target of great potential. The intriguing "Trojan horse" approach deprives microorganisms from the essential iron. Recently, gallium's potential in medicine as an iron mimicry species has attracted vast attention. Different Ga 3+ formulations exhibit diverse effects upon entering the cell and thus supposedly have multiple targets. The aim of the current study is to specifically distinguish characteristics of great significance in regard to the initial gallium-based complex, allowing the alien cation to effectively compete with the native ferric ion for binding the siderophores pyochelin and pyoverdine secreted by the bacterium P. aeruginosa . Therefore, three gallium-based formulations were taken into consideration: the first-generation gallium nitrate, Ga(NO 3 ) 3 , metabolized to Ga 3+ -hydrated forms, the second-generation gallium maltolate (tris(3-hydroxy-2-methyl-4-pyronato)gallium), and the experimentally proven Ga carrier in the bloodstream-the protein transferrin. We employed a reliable in silico approach based on DFT computations in order to understand the underlying biochemical processes that govern the Ga 3+ /Fe 3+ rivalry for binding the two bacterial siderophores.

In pursuit of discovering novel scaffolds that demonstrate potential inhibitory activity against p38α MAPK and possess strong antitumor effects, we herein report the design and synthesis of new series of 17 final target 5-(2,6-dichlorophenyl)-3-oxo-2,3-dihydro-5H-thiazolo[3,2-a]pyrimidine-7-carboxylic acids (4-20). Chemical characterization of the compounds was performed using FT-IR, NMR, elemental analyses and mass spectra of some representative examples. With many compounds showing potential inhibitory activity against p38α MAPK, two derivatives, 8 and 9, demonstrated the highest activity (>70 % inhibition) among the series. Derivative 9 displayed IC 50 value nearly 2.5 folds more potent than 8. As anticipated, they both showed explicit interactions inside the kinase active site with the key binding amino acid residues. Screening both compounds for cytotoxic effects, they exhibited strong antitumor activities against lung (A549), breast (MCF-7 and MDA MB-231), colon (HCT-116) and liver (Hep-G2) cancers more potent than reference 5-FU. Their noticeable strong antitumor activity pointed out to the possibility of an augmented DNA binding mechanism of antitumor action besides their kinase inhibition. Both 8 and 9 exhibited strong ctDNA damaging effects in nanomolar range. Further mechanistic antitumor studies revealed ability of compounds 8 and 9 to arrest cell cycle in MCF-7 cells at S phase, while in HCT-116 treated cells at G0-G1 and G2/M phases. They also displayed apoptotic induction effects in both MCF-7 and HCT-116 with total cell deaths more than control untreated cells in reference to 5-FU. Finally, the compounds were tested for their anti-migratory potential utilizing wound healing assay. They induced a significant decrease in wound closure percentage after 24 h treatment in the examined cancer cells when compared to untreated control MCF-7 and HCT-116 cells better than 5-FU. In silico computation of physicochemical parameters revealed the drug-like properties of 8 and 9 with no violation to Lipinski's rule of five as well as their tolerable ADMET parameters, thus suggesting their utilization as potential future drug leads amenable for further optimization and development., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

In an attempt to search for new natural product-based antitumor agents, a series of novel thiazolidinone derivatives of dehydroabietic acid-based B ring-fused-thiazole were designed and synthesized. The primary antitumor tests showed that compounds 5 m exhibited almost the best inhibitory activity against the tested cancer cells. The computational study suggested NOTCH1, IGF1R, TLR4, and KDR were the core targets of the title compounds, and the IC 50 of SCC9 and Cal27 is strong correlation with the binding ability of TLR4 and compounds., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Derivatives of thiazole-pyrazole fused benzo-coumarin compounds were successfully synthesized and characterized, followed by a comprehensive spectroscopic investigation on various photophysical properties in different media. The multipronged approach using steady state and time resolved fluorescence spectroscopy pointed out the impact of substitution in the estimated spectroscopic and other physicochemical properties of the systems. Further, the evaluation of anti-acetylcholinesterase (anti-AChE) activity yielded significant insight into the therapeutic potential of the synthesized coumarinyl compounds for the treatment of Alzheimer's disease (AD). The findings revealed a non-competitive mode of inhibition mechanism, with an estimated IC 50 value of 67.72 ± 2.00 nM observed for one of the investigated systems as AChE inhibitor. Notably, this value is even lower than that of an FDA-approved AD drug Donepezil (DON), indicating the enhanced potency of the coumarin derivatives in inhibiting AChE. Interestingly, significant diminution in inhibition was observed in presence of human serum albumin (HSA) as evidenced by the relative increase in IC 50 value by 8 ∼ 39 % in different cases, which emphasized the role of albumin proteins to control therapeutic efficacies of potential medications. In-depth spectroscopic and in-silico analysis quantified the nature of interactions of the investigated systems with HSA and AChE. Overall, the outcomes of this study provide significant understanding into the biophysical characteristics of novel thiazole-pyrazole fused benzo-coumarin systems, which could aid in the development of new cholinergic agents for the treatment of AD and materials based on coumarin motifs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

The bacillamides are a class of indole alkaloids produced by the Bacillus genus that possess significant antialgal activity. Incorporation of fluorine into the bacillamides was carried out using a precursor-directed biosynthesis approach, with 4-, 5-, and 6-fluorotryptophan added to growing cultures of Bacillus atrophaeus IMG-11. This yielded the corresponding fluorinated analogues of bacillamides A and C, in addition to new derivatives of the related metabolite N -acetyltryptamine, thus demonstrating a degree of plasticity in the bacillamide biosynthetic pathway. The bacillamide derivatives were tested for activity against bloom-forming algae, which revealed that fluorination could improve the antialgal activity of these compounds in a site-specific manner, with fluorination at the 6-position consistently resulting in improved activity.

The emergence of multi-drug-resistant bacteria is threatening to human health and life around the world. In particular, methicillin-resistant Staphylococcus aureus (MRSA) causes fatal injuries to human beings and serious economic losses to animal husbandry due to its easy transmission and difficult treatment. Currently, the development of novel, highly effective, and low-toxicity antimicrobials is important to combat MRSA infections. Thiazole-containing compounds with good biological activity are widely used in clinical practice, and appropriate structural modifications make it possible to develop new antimicrobials. Here, we review thiazole-containing compounds and their antibacterial effects against MRSA reported in the past two decades and discuss their structure-activity relationships as well as the corresponding antimicrobial mechanisms. Some thiazole-containing compounds exhibit potent antibacterial efficacy in vitro and in vivo after appropriate structural modifications and could be used as antibacterial candidates. This Review provides insights into the development of thiazole-containing compounds as antimicrobials to combat MRSA infections.

In a search for novel nonsugar α-glucosidase inhibitors for diabetes treatment, a series of N-(phenylsulfonyl)thiazole-2-carboxamide derivatives were designed and synthesized, the α-glucosidase inhibitory activities were then evaluated. Several compounds with promising α-glucosidase inhibitory effects were identified. Among these, compound W24 which shows low cytotoxicity and good α-glucosidase inhibitory activity with an IC 50 value of 53.0 ± 7.7 μM, is more competitive compared with the commercially available drug acarbose (IC 50  = 228.3 ± 9.2 μM). W24 was identified as a promising candidate in the development of α-glucosidase inhibitors. Molecular docking studies and molecular dynamics simulation were also performed to reveal the binding pattern of the active compound to α-glucosidase, and the binding free energy of the best compound W24 was 36.3403 ± 3.91 kcal/mol., (© 2023 Wiley Periodicals LLC.)

The present investigation aims to study adsorption-desorption behavior of glyphosate and tricyclazole in rice straw-compost biomixtures. To enhance pesticide adsorption and performance of the bio-purification system, rice straw-compost (BM) biomixture was mixed with wheat straw biochar (WBC, 1% and 5%), and adsorption of both pesticides in control (BM) and WBCBM(1%) and WBCBM(5%) biomixtures was compared. The kinetics study suggested that the pseudo-second-order model best explained the time-dependent adsorption of both pesticides and intraparticle adsorption was not the rate-determining step. Tricyclazole was more sorbed than glyphosate in all biomixtures which can be attributed to its lower water solubility. The WBC increased the sorption of both pesticides, but the effect varied with the nature of pesticides and biochar content. The adsorption coefficient values in BM, WBCBM(1%), and WBCBM(5%) biomixtures were 26.74, 38.16, and 51.97 (glyphosate) and 38.07, 59.94, and 84.54 (tricyclazole), respectively. The adsorption data was subjected to the Freundlich, the Langmuir, and the Temkin isotherms, and among them, the Freundlich isotherm best explained pesticide adsorption behavior. Desorption results suggested that the adsorption of glyphosate was more irreversible than tricyclazole and depended upon initial pesticide concentration. This study suggested that biochar mixed rice straw-compost biomixtures can be exploited in bio-purification systems for glyphosate and tricyclazole.

Aim: Novel thiazole hybrids were synthesized via thiazolation of 4-phenylthiosemicarbazone ( 4 ). Materials & methods: The anticancer activity against the NCI 60 cancer cell line panel. Results: Methyl 2-(2-((1-(naphthalen-2-yl)ethylidene)hydrazineylidene)-4-oxo-3-phenylthiazolidin-5-ylidene)acetate ( 6a ) showed significant anticancer activity at 10 μM with a mean growth inhibition (GI) of 51.18%. It showed the highest cytotoxic activity against the ovarian cancer OVCAR-4 with an IC 50 of 1.569 ± 0.06 μM. Compound 6a inhibited PI3Kα with IC 50  = 0.225 ± 0.01 μM. Moreover, compound 6a revealed a decrease of Akt and mTOR phosphorylation in OVCAR-4 cells. In addition, antibacterial activity showed that compounds 11 and 12 were the most active against Staphylococcus aureus . Conclusion: Compound 6a is a promising molecule that could be a lead candidate for further studies.

Background: Thiazole is a widely studied core structure in heterocyclic chemistry and has proven to be a valuable scaffold in medicinal chemistry. The presence of thiazole in both naturally occurring and synthetic pharmacologically active compounds demonstrates the adaptability of these derivatives., Methods: The current study attempted to review and compile the contributions of numerous researchers over the last 20 years to the medicinal importance of these scaffolds, with a primary focus on antimalarial activity. The review is based on an extensive search of PubMed, Google Scholar, Elsevier, and other renowned journal sites for a thorough literature survey involving various research and review articles., Results: A comprehensive review of the antimalarial activity of the thiazole scaffold revealed potential therapeutic targets in Plasmodium species. Furthermore, the correlation of structure-activity-relationship (SAR) studies from various articles suggests that the thiazole ring has therapeutic potential., Conclusion: This article intends to point researchers in the right direction for developing potential thiazole-based compounds as antimalarial agents in the future., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: This review summarizes data on heterocyclic systems with thiadiazole and thiazole fragments in molecules as promising antimicrobial agents., Introduction: Thiadiazole and thiazole backbones are the most favored and well-known heterocycles, a common and essential feature of various drugs. These scaffolds occupy a central position and are the main structural components of numerous drugs with a wide spectrum of action. These include antimicrobial, antituberculous, anti-inflammatory, analgesic, antiepileptic, antiviral, and anticancer agents., Method: The research is based on bibliosemantic and analytical methods using bibliographic and abstract databases, as well as databases of chemical compounds., Result: This review reports on thiadiazole and thiazole derivatives, which have important pharmacological properties. We are reviewing the structural modifications of various thiadiazole and thiazole derivatives, more specifically, the antimicrobial activity reported over the last years, as we have taken this as our main research area. 80 compounds were illustrated, and various derivatives containing hydrazone bridged thiazole and pyrrole rings, 2-pyridine and 4-pyridine substituted thiazole derivatives, compounds containing di-, tri- and tetrathiazole moieties, spiro-substituted 4- thiazolidinone-imidazoline-pyridines were analyzed. Derivatives of 5-heteroarylidene-2,4- thiazolidinediones, fluoroquinolone-thiadiazole hybrids, and others., Conclusion: 1,3,4-thiadiazoles and thiazoles are valuable resource for researchers engaged in rational drug design and development in this area., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: A series of 15 thiazolyl hydrazone derivatives of chromone-3- carbaldehyde have been designed and synthesized by the cyclization of thiosemicarbazone derivatives of chromone-3-carbaldehydes with 4'-substituted-2-bromo acetophenones., Methods: All these derivatives were evaluated for antioxidant activity by their direct scavenging activity objects to reactive oxygen species such as DPPH, and nitric oxide, as well as in vitro antiinflammatory activity by a protein denaturation method. Most of these synthesized compounds have shown significant antioxidant activity, among which the compounds 5b, 5c, 5e, 5g, and 5j showed very good antioxidant activities in comparison with the standard ascorbic acid. The in vitro anti-inflammatory activity revealed that the compounds 5b, 5g, and 5h possessed significant activity compared to standard diclofenac sodium., Results: Additionally, molecular docking studies of these molecules using ovalbumin as the protein showed remarkable interactions with its active site residues, and the results indicated that the binding mode of these compounds closely resembled that of the reference compound, diclofenac sodium., Conclusion: Thus, these compounds represent an attractive template for the evaluation of new antiinflammatory and antioxidant agents and might be useful for exploring new therapeutic tools., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Aim: p-Toluenesulfonic acid-(PTSA) and grinding-induced novel synthesis of ethylquinolin-thiazolo-triazole derivatives was performed using green chemistry. Materials & methods: Development of a nanoconjugate drug-delivery system of ethylquinolin-thiazolo-triazole was carried out with D-α-tocopheryl polyethylene glycol succinate (TPGS) and the formulation was further characterized by transmission electron microscopy, atomic force microscopy, dynamic light scattering and in vitro drug release assay. The effect of 3a nanoparticles was assessed against a cervical cancer cell line (HeLa) through the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and the effect on apoptosis was determined. Results & discussion: The 3a nanoparticles triggered the apoptotic mode of cell death after increasing the intracellular reactive oxygen level by enhancing cellular uptake of micelles. Furthermore, in silico studies revealed higher absorption, distribution, metabolism, elimination and toxicity properties and bioavailability of the enzyme tyrosine protein kinase. Conclusion: The 3a nanoparticles enhanced the therapeutic potential and have higher potential for targeted drug delivery against cervical cancer.

Aim: To synthesize novel more potent anti-diabetic agents. Methodology: A simple cost effective Hantzsch's synthetic strategy was used to synthesize 2-(2-arylidenehydrazinyl)thiazol-4(5 H )-ones. Results: Fifteen new 2-(2-arylidenehydrazinyl)thiazol-4(5 H )-ones were established to check their anti-diabetic potential. From alpha(α)-amylase inhibition, anti-glycation and anti-oxidant activities it is revealed that most of the compounds possess good anti-diabetic potential. All tested compounds were found to be more potent anti-diabetic agents via anti-glycation mode. The results of α-amylase and anti-oxidant inhibition revealed that compounds are less active against α-amylase and anti-oxidant assays. Conclusion: This study concludes that introduction of various electron withdrawing groups at the aryl ring and substitution of different functionalities around thiazolone nucleus could help to find out better anti-diabetic drug.

Aim: Efficient synthesis of precursor from commercially available starting materials and automated radiosynthesis of [ 11 C]PiB using commercially available dedicated [ 11 C]- Chemistry module from the synthesized precursor., Background: [ 11 C]PiB is a promising radiotracer for PET imaging of β-Amyloid, advancing Alzheimer's disease research. The availability of precursors and protocols for efficient radiolabelling foster the applications of any radiotracer. Efficient synthesis of PiB precursor was performed using anisidine and 4-nitrobenzoyl chloride as starting materials in 5 steps, having addition, substitutions, and cyclization chemical methodologies. This precursor was used for fully automated radiosynthesis of [ 11 C]PiB in a commercially available synthesizer, MPS-100 (SHI, Japan). The synthesized [ 11 C]PiB was purified via solid-phase methodology, and its quality control was performed by the quality and safety criteria required for clinical use., Methods: The synthesis of desired precursors and standard authentic compounds started with commercially available materials with 70-80% yields. The standard analytical methods were characterized all synthesized compounds. The fully automated [ 11 C]-chemistry synthesizer (MPS-100) used for radiosynthesis of [ 11 C]PiB with [ 11 C]CH 3 OTf acts as a methylating agent. For radiolabelling, varied amounts of precursor and time of reaction were explored. The resulting crude product underwent purification through solid-phase cartridges. The synthesized radiotracer was analyzed using analytical tools such as radio TLC, HPLC, pH endo-toxicity, and half-life., Results: The precursor for radiosynthesis of [ 11 C]PiB was achieved in excellent yield using simple and feasible chemistry. A protocol for radiolabelling of precursor to synthesized [ 11 C]PiB was developed using an automated synthesizer. The crude radiotracer was purified by solid-phase cartridge, with a decay-corrected radiochemical yield of 40±5% and radiochemical purity of more than 97% in approx 20 minutes (EOB). The specific activity was calculated and found in a 110-121 mCi/μmol range., Conclusion: A reliable methodology was developed for preparing precursor followed by fully automated radiolabeling using [ 11 C]MeOTf as a methylating agent to synthesize [ 11 C]PiB. The final HPLC-free purification yielded more than 97% radiochemical purity tracer within one radionuclide half-life. The method was reproducible and efficient for any clinical center., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: The Fibroblast Growth Factor Receptor-1 (FGFR-1) is a tyrosine kinase and a validated target for the treatment of different cancer types., Objective: Design and synthesis of novel thiazole-based analogues of anticancer agents., Methods: Series of 2-aryl-5-methylthiazole analogues linked to structurally variable basic heads were synthesized as novel anticancer agents. Developed compounds were tested for their cytotoxic activities against several cancer cell lines., Results: Many analogues exhibited strong antiproliferative activities against breast cancer cell lines, with higher potency towards the highly metastatic form (MDA-MB-231). Pharmacophoric profiling using an in-house pharmacophore database identified FGFR-1 as a molecular target of active analogues. Synthesized compounds were bioassayed for their FGFR-1 inhibitory activities and many hits exhibited IC50 values in the low micromolar to nanomolar range., Conclusion: The 2-aryl-5-methylthiazole linked to a basic head is a novel chemical scaffold of ATP-competitive inhibitor of FGFR-1 with potential therapeutic activities against different types of cancer., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Cancer is a disease characterized by the abnormal multiplication of cells and is the second leading cause of death in the world. The search for new effective and safe anticancer compounds is ongoing due to factors such as low selectivity, high toxicity, and multidrug resistance. Thus, heterocyclic compounds derived from isatin, thiazole and phthalimide that have achieved promising in vitro anticancer activity have been tested in vivo and in clinical trials., Objective: This review focused on the compilation of promising data from thiazole, isatin, and phthalimide derivatives, reported in the literature between 2015 and 2022, with in vivo anticancer activity and clinical trials., Methods: A bibliographic search was carried out in the PUBMED, MEDLINE, ELSEVIER, and CAPES PERIODIC databases, selecting relevant works for each pharmacophoric group with in vivo antitumor activity in the last 6 years., Results: In our study, 68 articles that fit the scope were selected and critically analyzed. These articles were organized considering the type of antitumor activity and their year of publication. Some compounds reported here demonstrated potent antitumor activity against several tumor types., Conclusion: This review allowed us to highlight works that reported promising structures for the treatment of various cancer types and also demonstrated that the privileged structures thiazole, isatin and phthalimide are important in the design of new syntheses and molecular optimization of compounds with antitumor activity., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Nosiheptide (NOS) is a thiopeptide antibiotic produced by the bacterium Streptomyces actuosus. The hydroxyl group of 3-hydroxypyridine in NOS has been identified as a promising site for modification, which we therefore aimed to rhamnosylate. After screening, Streptomyces sp. 147326 was found to regioselectively attach a rhamnosyl unit to the 3-hydroxypyridine site in NOS, resulting in the formation of a derivative named NOS-R at a productivity of 24.6%. In comparison with NOS, NOS-R exhibited a 17.6-fold increase in aqueous solubility and a new protective effect against MRSA infection in mice, while maintaining a similar in vitro activity. Subsequently, SrGT822 was identified as the rhamnosyltransferase in Streptomyces sp. 147326 responsible for the biosynthesis of NOS-R using dTDP-L-rhamnose. SrGT822 demonstrated an optimal reaction pH of 10.0 and temperature of 55°C, which resulted in a NOS-R yield of 74.9%. Based on the catalytic properties and evolutionary analysis, SrGT822 is anticipated to be a potential rhamnosyltransferase for use in the modification of various complex scaffolds., (© 2024 The Authors. Microbial Biotechnology published by Applied Microbiology International and John Wiley & Sons Ltd.)

The thiazole ring is naturally occurring and is primarily found in marine and microbial sources. It has been identified in various compounds such as peptides, vitamins (thiamine), alkaloids, epothilone, and chlorophyll. Thiazole-containing compounds are widely recognized for their antibacterial, antifungal, anti-inflammatory, antimalarial, antitubercular, antidiabetic, antioxidant, anticonvulsant, anticancer, and cardiovascular activities. The objective of this review is to present recent advancements in the discovery of biologically active thiazole derivatives, including their synthetic methods and biological effects. This review comprehensively discusses the synthesis methods of thiazole and its corresponding biological activities within a specific timeframe, from 2017 until the conclusion of 2022., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: 4-Methylacetophenone is used in the preparation of starting materials, 4-methylphenacyle bromide ( 2 ) and 4-methylacetophenone thiosemicarbazole ( 3 ). Results: Several novel 2,4-disubstituted-1,3-thiazole analogues were obtained via the treatment of starting materials with 4-methylphenacyl bromide, acetyl chloride, aromatic aldehydes and bromination providing thiazole derivatives 5-8 respectively. Conclusion: Compounds 5-8 were investigated for their cytotoxic activity on MCF-7 and normal breast cells. Active compounds were found and in contrast to staurosporine, compound 8 displayed the most potent cytotoxic action that showed a strong inhibitory effect (aromatase) and (protein tyrosine kinase) enzymes, proving that the novel thiazole derivatives promoted the effective anticancer drug candidates.