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The current study was aimed to synthesize a series of adamantane-linked aminothiazole derivatives (6a-) and to assess their enzyme inhibitory activities. These derivatives were synthesized based on the structural features of known enzyme inhibitors, and their structures were characterized using various spectroscopic techniques, including FTIR, 1H NMR, 13C NMR, and mass spectrometry. The synthesized compounds were further evaluated for their inhibitory activities against the enzymes urease, α-glucosidase and carbonic anhydrase. The results of the enzyme inhibitory activity showed that compounds 6c, 6g and 6k possessed an excellent urease inhibitory activities, with IC50 values of 18.07 ± 0.11, 13.05 ± 0.2 and 17.12 ± 0.1 µM, respectively. These values were significantly lower than the IC50 value of the standard inhibitor thiourea (21,021 ± 0.02 µM). Additionally, compound 6c and 6e showed good α-glucosidase inhibitory activities. Therefore, compound 6c and 6e has excellent activity of IC50 value as 18.4 ± 0.11 and 58.01 ± 0.8 µM against α-glucosidase enzyme, respectively, and considerable relative potency compared with the known α-glucosidase inhibitor i.e., acarbose having an IC50 value of 883.93 ± 2.18 µM. The inhibitory effect of the compound 6f, 6k, 6j was considerably high against carbonic anhydrase, with their IC50 values of 3.02 ± 0.31 µM, 4.5 ± 0.041 µM and 2.7 ± 0.004 µM, respectively, as compared to acetazolamide with an IC50 value of IC50 0.12 ± 0.03 µM. The molecular docking of the active compounds docked in the active site of urease, α-glucosidase enzyme and carbonic anhydrase and depicted a good-binding score for all active derivatives. The present results indicate the significance of the structure–activity relationship in the development of potent enzyme inhibitors. Hence, the results obtained from the current study may be useful for designing further studies on related compounds with potential medicinal importance. [ABSTRACT FROM AUTHOR]

Epileptogenic seizures, or status epilepticus (SE), leads to excitotoxic injury in hippocampal and limbic neurons in the kainic acid (KA) animal model of temporal lobe epilepsy (TLE). Here, we have further characterized neural activity regulated methylaminoisobutryic acid (MeAIB)/glutamine transport activity in mature rat hippocampal neurons in vitro that is inhibited by riluzole (IC50 = 1 μM), an anti-convulsant benzothiazole agent. We screened a library of riluzole derivatives and identified SKA-41 followed by a second screen and synthesized several novel chlorinated aminothiazoles (SKA-377, SKA-378, SKA-379) that are also potent MeAIB transport inhibitors in vitro, and brain penetrant following systemic administration. When administered before KA, SKA-378 did not prevent seizures but still protected the hippocampus and several other limbic areas against SE-induced neurodegeneration at 3d. When SKA-377 - 379, (30 mg/kg) were administered after KA-induced SE, acute neural injury in the CA3, CA1 and CA4/hilus was also largely attenuated. Riluzole (10 mg/kg) blocks acute neural injury. Kinetic analysis of SKA-378 and riluzoles' blockade of Ca2+-regulated MeAIB transport in neurons in vitro indicates that inhibition occurs via a non-competitive, indirect mechanism. Sodium channel NaV1.6 antagonism blocks neural activity regulated MeAIB/Gln transport in vitro (IC50 = 60 nM) and SKA-378 is the most potent inhibitor of NaV1.6 (IC50 = 28 μM) compared to NaV1.2 (IC50 = 118 μM) in heterologous cells. However, pharmacokinetic analysis suggests that sodium channel blockade may not be the predominant mechanism of neuroprotection here. Riluzole and our novel aminothiazoles are agents that attenuate acute neural hippocampal injury following KA-induced SE and may help to understand mechanisms involved in the progression of epileptic disease.

In this study, ten novel disazo dyes based on aminothiazoles (4a-e, 5a-e) were synthesized in the first section. By using their 1H-NMR, FT-IR, and UV-Vis spectra, these synthesized dyes' structures were verified. In the second section, the density functional theory (DFT) was used to calculate the molecular geometry, vibrational frequency and molecular electrostatic potential (MEP) diagram in the ground state using the B3LYP level and the 6-311 G(d,p) basis set. UV-vis data were obtained using the Gaussian 09 TD-DFT Cam-B3LYP 6-311 G ++ (d,p) basis set. To explore the chemical shift values, the gauge independent atomic orbital (GIAO) approach was used. Time-dependent DFT (TD-DFT) approach was used to determine the HOMO–LUMO calculations. As a consequence of our research, it was found that the experimental values and the computational spectroscopic values of the synthesized disazo compounds were consistent. [ABSTRACT FROM AUTHOR]

Among sulfur- and nitrogen-containing heterocyclic compounds, the aminothiazole scaffold is one of the most unique architectures in drug development, since it comprises a variety of biological effects. Furthermore, numerous aminothiazole-based compounds have been widely used as medical drugs to treat a range of illnesses, resulting in a slew of new inventions. The synthetic procedures employed to get new aminothiazole derivatives from enaminonitrile acrylamide derivative 2, which was previously used as a key step in the synthesis of pyrazole, isoxazole, and pyrimidine derivatives, are innovative (4, 6 and 8). In addition, enaminonitrile 2 showed chemical activity toward some N-nucleophiles such as heterocyclic amines for synthesis triazolo, imidazo and pyrazolo pyrimidine derivatives (10, 12, and 14). Enaminonitrile precursor 2 was cyclocondensed with various carbon and oxygen nucleophiles to provide some complex polyfunctionally substituted fused 2-pyridone and chromenone derivatives with a thiazoyl sulfonamido moiety (16, 18, 20, and 24). The anticancer efficacy of all novel aminothiazoles was tested in vitro against human prostate carcinoma (PC3) utilizing normal prostate epithelial cell line (PNT2) as control cells. The most powerful derivatives against prostate cancer cell lines were determined to be 14 and 16, which had no impact on normal cells. Compound 20 on the other hand, has just mediocre anticancer properties. [ABSTRACT FROM AUTHOR]

4-Fluoro- N -(thiazol-2-yl)benzenesulfonamide (3) is a novel fluorinated compound, containing various biological activities. Therefore, absorption spectroscopy, fluorescence quenching, molecular docking, and molecular simulation were employed to investigate the interaction between 3 and human serum albumin (HSA). Firstly, compound 3 meets all criteria for drug-likeness prediction. UV absorption spectra revealed the interaction of 3 with HSA altered the microenvironment of protein, as well as circular dichroism spectroscopic analysis indicated slightly conformational changes and a reduction in α-helical content. The binding parameters of the HSA– 3 complex suggested that fluorescence quenching is driven by combined static and dynamic processes. Additionally, the stability of the complex is attributed to conventional hydrogen and hydrophobic bonding interactions. Furthermore, esterase-like activity indicated that the binding of 3 might disrupt HSA's bond networks, leading to structural alterations. Consequently, the strong binding constant (K a ≈ 1.204 × 106 M–1) aligns with the predicted unbound fraction (0.28) in serum, indicating that thiazole 3 has good bioavailability in plasma and can be effectively transported to target sites, thereby exerting its pharmaceutical effects. However, careful dosage management is essential to prevent potential adverse effects. Overall, these findings highlight the potential of 3 as a therapeutic agent, emphasizing the need for further research to optimize its uses. [Display omitted] [ABSTRACT FROM AUTHOR]

The title compound, [Fe(C5H5)(C8H7N2S)], was synthesized by the direct reaction of acetylferrocene, thiourea and resublimed iodine. The structure shows one molecule in the asymmetric unit. The aminothiazole ring makes an angle of 14.53 (13)° with the ferrocenyl ring to which it is attached. In the crystal, pairs of complex molecules interact via intermolecular N—H...N hydrogen bonds, forming a cyclic dimer which then interacts with other dimers through C—H...π interactions.

The experimental density, viscosity, and ultrasonic velocities of 2-aminothiazole (2-AT) and alkanols namely; methanol (MeOH), ethanol (EtOH), and propanol (PrOH) have been measured over the full range of compositions at different temperatures (303.15, 308.15, 313.15, 318.15, and 323.15 K). From these experimental values the adiabatic compressibility (βad), intermolecular free length (Lf), acoustic impedance (z), relative association (RA), relaxation time (τ), and internal pressure (π) were computed. [ABSTRACT FROM AUTHOR]

Antimicrobial drug resistance is currently one of the most critical health issues. Pathogens resistant to last-resort antibiotics are increasing, and very few effective antibacterial agents have been introduced in recent years. The promising drug candidates are often discontinued in the primary stages of the drug discovery pipeline due to their unspecific reactivity (PAINS), toxicity, insufficient stability, or low water solubility. In this work, we investigated a series of substituted N-oxazolyl- and N-thiazolylcarboxamides of various pyridinecarboxylic acids. Final compounds were tested against several microbial species. In general, oxazole-containing compounds showed high activity against mycobacteria, especially Mycobacterium tuberculosis (best MICH37Ra = 3.13 µg/mL), including the multidrug-resistant strains. Promising activities against various bacterial and fungal strains were also observed. None of the compounds was significantly cytotoxic against the HepG2 cell line. Experimental measurement of lipophilicity parameter log k'w and water solubility (log S) confirmed significantly (typically two orders in logarithmic scale) increased hydrophilicity/water solubility of oxazole derivatives in comparison with their thiazole isosteres. Mycobacterial β-ketoacyl-acyl carrier protein synthase III (FabH) was suggested as a probable target by molecular docking and molecular dynamics simulations. [ABSTRACT FROM AUTHOR]

Herbicides used to fight with allopathic plants causing harmful effect in agricultural lands are very important to obtain good agricultural products. To interpret of herbicidal effect a series of original compounds synthesized to investigate phytotoxic effects. For this, firstly, 2-acetylbenzimidazole has been obtained with many steps. After, it has been condensed 2-aminothiazole ring from second position of benzimidazole. After that, the amino group has been transformed to thiourea. After all of these steps, the all needed starting materials have been synthesized to attain the desired target compounds. Finally, the prepared arylacetyl bromide compounds and the starting compounds have been reacted with each other and formed new thiazole rings thus, target compounds have been synthesized. The synthesized 2-(4-(1-Substitutedbenzimidazole-2-yl)thiazole-2-ylamino)-4-arylthiazole derivatives as target compounds are novel compounds and their structures has been elucidated by using elemental analysis; IR, NMR and MS spectral data. The synthesized compounds have been tested on seeds of Lepidium sativum L. (cress) to study of their biological activities. Consequently, it was found that these compounds have phytotoxic effects based on their biological activities.

Transmembrane protein 16A (TMEM16A), also called Ano1, is a Ca(2+) activated Cl(-) channel expressed widely in mammalian epithelia, as well as in vascular smooth muscle and some tumors and electrically excitable cells. TMEM16A inhibitors have potential utility for treatment of disorders of epithelial fluid and mucus secretion, hypertension, some cancers and other diseases. 4-Aryl-2-amino thiazole T16Ainh-01 was previously identified by high-throughput screening. Here, a library of 47 compounds were prepared that explored the 5,6-disubstituted pyrimidine scaffold found in T16Ainh-01. TMEM16A inhibition activity was measured using fluorescence plate reader and short-circuit current assays. We found that very little structural variation of T16Ainh-01 was tolerated, with most compounds showing no activity at 10 μM. The most potent compound in the series, 9bo, which substitutes 4-methoxyphenyl in T16Ainh-01 with 2-thiophene, had IC50 ∼1 μM for inhibition of TMEM16A chloride conductance.

The reactivity of α-azidochalcones has been explored for the preparation of highly substituted oxazoles via a 2H-azirine intermediate. The azidochalcones, when treated with potassium thiocyanate in the presence of potassium persulfate, lead to 2,4,5-trisubstituted oxazoles in good yields. Incidentally, 2-aminothiazoles are the products when ferric nitrate is employed instead of persulfate in the above reaction.

• An aminothiazole derivative X22 showed a significant reduction in the levels of inflammatory mediators including NO, TNF-α and IL-6 in RAW 264.7 cells stimulated with LPS. • MEP revealed that the reactive sites are located in CF 3 and NH 2 groups. These particular groups exhibit a strong propensity to engage in hydrogen bonding and dipole-dipole interactions. • Molecular docking studies revealed that ligand (X22) binds to TNF-α and IL-6 via H-bonding with amino acids, Tyr151, Ser60, Gln61, and Arg179. • MD simulation data demonstrated that TNF-alpha exhibits effective binding to the active sites of proteins, resulting in the formation of a stable protein complex. Aminothiazole-based structures, including compounds like anakinra, nitazoxanide, amiphenazole, and tizoxanide, along with cytokine-blocking agents such as tocilizumab and siltuximab are currently under extensive investigation for their potential in managing severe COVID-19 by specifically targeting and inhibiting cytokines responsible for cytokine release syndrome (CRS). These targeted therapies have shown promising results in effectively mitigating the effects of severe COVID-19. Herein, we carried out a biological assessment of a novel aminothiazole-based derivative 5-(phenylthio)-4-(2-(trifluoromethyl) phenyl) thiazol-2-amine (X22) to gauge its potential as an anti-inflammatory agent. Utilizing in vitro assays, which included measuring nitric oxide (NO) inhibition and observing the production of LPS-induced pro-inflammatory cytokines (TNF-α and IL-6) in RAW 264.7 macrophages. Furthermore, the X22 was characterized by experimental FT-IR, NMR, and UV–visible spectral analysis. The optimized molecular geometry and vibrational wave numbers were calculated using the DFT and B3LYP/6–311++ G (d,p) basis set. The vibrational assignments were calculated using VEDA's Potential Energy Distribution (PED) program. 1H and 13C NMR were calculated by the GIAO method. Additionally, compounds HOMO-LUMO and HF interactions were studied. Subsequently, the MEP map was traced to find the reactive sites of X22. In addition, Mulliken population analysis and thermodynamic properties with respect to various temperatures were also calculated. All the theoretical predictions were carried out by using the DFT-B3LYP method at the level of 6–311++ G (d,p). Finally, the molecular docking interactions revealed that ligand (X22) binds to TNF-α and IL-6 via H-bonding with amino acids Tyr 151, Ser60, Gln61, and Arg179. These findings suggest that X22 could be a valuable therapeutic agent for mitigating the progression of severe SARS-CoV-2 infections. [Display omitted] [ABSTRACT FROM AUTHOR]

Antimicrobial drug resistance is currently one of the most critical health issues. Pathogens resistant to last-resort antibiotics are increasing, and very few effective antibacterial agents have been introduced in recent years. The promising drug candidates are often discontinued in the primary stages of the drug discovery pipeline due to their unspecific reactivity (PAINS), toxicity, insufficient stability, or low water solubility. In this work, we investigated a series of substituted N-oxazolyl- and N-thiazolylcarboxamides of various pyridinecarboxylic acids. Final compounds were tested against several microbial species. In general, oxazole-containing compounds showed high activity against mycobacteria, especially Mycobacterium tuberculosis (best MICH37Ra = 3.13 µg/mL), including the multidrug-resistant strains. Promising activities against various bacterial and fungal strains were also observed. None of the compounds was significantly cytotoxic against the HepG2 cell line. Experimental measurement of lipophilicity parameter log k’w and water solubility (log S) confirmed significantly (typically two orders in logarithmic scale) increased hydrophilicity/water solubility of oxazole derivatives in comparison with their thiazole isosteres. Mycobacterial β-ketoacyl-acyl carrier protein synthase III (FabH) was suggested as a probable target by molecular docking and molecular dynamics simulations.

Aim: The objective of the present study was to design, synthesize and evaluate diverse Schiff bases and thiazolidin-4-one derivatives of aminothiazole as key pharmacophores possessing acetylcholinesterase inhibitory activity. Materials & methods: Two series of compounds (13 each) were synthesized and evaluated for their acetylcholinesterase inhibition and antioxidant activity. Molecular docking of all compounds was performed to provide an insight into their binding interactions. Results: Compounds 2j (IC 50  = 0.03 μM) and 3e (IC 50  = 1.58 μM) were found to be the best acetylcholinesterase inhibitors among compounds of their respective series. Molecular docking analysis supported the results of in vitro activity by displaying good docking scores with the binding pocket of human acetylcholinesterase (Protein Data Bank ID: 4EY7). Conclusion: Compound 2j emerged as a potential lead compound with excellent acetylcholinesterase inhibition, antioxidant and chelation activity.

Two series of novel thiazolylcarboxamide derivatives were synthesized by the reaction of ethyl 2-amino-4-methylthiazole-5-carboxylate or 1-(2-amino-4-methylthiazol-5-yl)ethan-1-one with four substituted carbonyl chlorides at 0 °C in excellent yield. All products were characterized by FTIR, 1H NMR spectroscopy and mass spectrometry. Crystal structures of four compounds were studied by X-ray analysis. All the synthesized compounds were screened against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus pyogenes for antibacterial activity and against Candida albicans, Aspergillusniger and Aspergillus clavatus for antifungal activity. Present study describes the biological activity and crystal structure study of carboxamides obtained from 2-aminothaizol derivatives. Owing to the insolubility of these amides in single volatile solvent, crystals were grown in a mixture of solvents. [ABSTRACT FROM AUTHOR]

This study represents a successful and simple method for printing and finishing polyester fabrics by adapting a new aminothiazole disperse dye and microwave technique. Microwave pretreatment of polyester fabrics was carried out under a variety of conditions in terms of the microwave power and time. Afterwards, the printed samples were fixed using both conventional techniques and microwave energy. The color strength expressed as K/S of the printed samples was evaluated in addition to CIELAB coordinates (L*, a*, and b*), which were also measured. Washing, rubbing, and light fastness properties were evaluated for samples prepared by both conventional and microwave fixation techniques. Scanning electron microscopy (SEM) was used to investigate the morphological characteristics of the treated printed samples. The biological activity of the synthesized dye against gram-positive bacteria and gram-negative bacteria was also evaluated. The obtained results clarified that the prints obtained using microwave treatment and new dyes have better color strength, stable brilliant color, good fastness properties, and highly durable antibacterial activity when compared to those of conventional techniques using thermofixation and steaming. [ABSTRACT FROM AUTHOR]

[Display omitted] • The CFP electrode is modified with biomass-derived Carbon quantum dots decorated aminothiazole (CQD-AT/CFP) composite developed. • An electrochemical sensor has been used to detect dual heavy metal ions using the square wave anodic stripping voltammetric technique (SWASV) technique. • A novel electrochemical sensor for Pb2+ and Hg2+ metal ions was established. • These synthesized electrochemical sensor acts as excellent sensing probe for the selective and sensitive detection of heavy metal ions in industrial effluents. A novel electrochemical sensor capable of concurrently detecting Pb2+ and Hg2+ ions has been innovatively engineered. This sensor utilizes the anodic stripping voltammetry technique (ASV) with a composite consisting of carbon quantum dots and aminothiazole (CQD-AT). In this composite, both the carbon quantum dots and aminothiazole contribute significantly to the electroactive surface area, boasting an abundance of functional groups that include oxygen and nitrogen atoms. These functional groups serve as active sites that enhance sensor sensitivity by facilitating the electrostatic interaction-based adsorption of heavy metal ions. Aminothiazole surface is evenly covered with CQDs, which are essential for metal gets reoxidized into metal ions for stripping analysis. Due to this unique modification, the Pb2+ and Hg2+ electrochemical sensor using the CQD-AT composite coated on carbon fiber paper electrode (CQD-AT/CFP) exhibits superior analysis performance such as wide linear range (0.6 × 10–11–160 × 10–6 M) for Pb2+ and Hg2+ with a limit of detection (LOD) of 3.0 pM and 6.2 pM for Pb2+ and Hg2+. CQD-AT/CFP modified electrode can be considered as a potential material for electrochemical simultaneous determination of Pb2+ and Hg2+ in different water samples. [ABSTRACT FROM AUTHOR]

A series of novel hybrid compounds containing benzofuroxan and 2-aminothiazole moieties are synthesized via aromatic nucleophilic substitution reaction. Possible reaction pathways have been considered quantum-chemically, which allowed us to suggest the most probable products. The quantum chemical results have been proved by X-ray data on one compound belonging to the synthesized series. It was shown that the introduction of substituents to both the thiazole and amine moieties of the compounds under study strongly influences their UV/Vis spectra. Initial substances and obtained hybrid compounds have been tested in vitro as anticancer agents. Target compounds showed selectivity towards M-HeLa tumor cell lines and were found to be more active than starting benzofuroxan and aminothiazoles. Furthermore, they are considerably less toxic to normal liver cells compared to Tamoxifen. The mechanism of action of the studied compounds can be associated with the induction of apoptosis, which proceeds along the mitochondrial pathway. Thus, new hybrids of benzofuroxan are promising candidates for further development as anticancer agents.

2‐aminothiazole monomer (AT‐monomer) and polymer (AT‐polymer) are utilized as the nitrogen source to synthesize the Fe/N/C catalysts. The polymerization effect of nitrogen source for Fe/N/C catalysts on their bifunctional activity toward oxygen reduction reaction (ORR) and CO2 reduction reaction (CO2RR) is investigated. Both AT‐monomer‐Fe/N/C and AT‐polymer‐Fe/N/C contain pyridine N (including Fe−N) and graphitic N in the structure, resulting in displaying bifunctional activity toward ORR and CO2RR. The 2‐aminothiazole polymer structure is important to produce graphene structured nanosheets with higher amount of defect sites and more pyridinic N (including Fe−N) and graphitic N in AT‐polymer‐Fe/N/C than those in AT‐monomer‐Fe/N/C synthesized from 2‐aminothiazole monomers. With the structure advantages, AT‐polymer‐Fe/N/C displays superior bifunctional catalytic performance. It has higher catalytic efficiency than commercial Pt/C for ORR and high CO selectivity (92%) with 4.2 mA cm–2 at overpotential of 0.47 V for CO2RR than that of AT‐monomer‐Fe/N/C. [ABSTRACT FROM AUTHOR]

Crystallography has identified stearic acid, ALRT 1550 and ATRA as ligands that bind RORβ, however, none of these molecules represent good starting points to develop optimized small molecule modulators. Recently, Compound 1 was identified as a potent dual RORβ and RORγ inverse agonist with no activity towards RORα (Fig. 1). To our knowledge, this is one of only two small molecule RORβ inverse agonists identified in the primary literature from a tractable chemical series and represents an ideal starting point from which to design RORβ-selective modulators. Herein we describe our SAR optimization efforts that led to a series of potent neutral antagonists of RORβ. [ABSTRACT FROM AUTHOR]

An efficient, aminothiazole based, fluorescent probe ( E )-2-(2-aminothiazol-5-yl)- N '-((2-hydroxynaphthalen-1-yl)methylene)acetohydrazide (NTH) for the detection of Al 3+ ions was synthesized and characterized by different physico-chemical and spectroscopic tools. An attractive glowing blue color was observed in the presence of Al 3+ with single channel emissions for NTH (λ em 451 & λ ex 391 nm). NTH, selectively detected Al 3+ ions among various other ions without any significant interference in Tris-HCl buffer solution (10 mM, pH ∼ 7.4). The >C N isomerization was responsible for the turn ‘on’ fluorescence response after Al 3+ binding. The stoichiometry of NTH with Al 3+ was determined to be 1:1 by Job’s plot. The binding constant and limit of detection (LOD) were observed as 3.65 × 10 9 M −1 and 1.09 × 10 −9 M, respectively. The 1 H NMR titration and DFT studies were also performed in support of binding details of NTH-Al 3+ complex. MTT assay on live A549 cells suggested viability of the probe to A549 cells even at higher concentration (100 μM) with no serious cytotoxicity in cells. Live cell imaging study clearly indicated that the accumulation of Al 3+ in the cytoplasm of cells could be detected by NTH. [ABSTRACT FROM AUTHOR]

Aminothiazole organic compounds have diverse biological applications. Herein we report the synthesis of two aminothiazole derivatives: 4-(biphenyl-4-yl)thiazol-2-amine ( 1 ) and 4-(2′,4′-difluorobiphenyl-4-yl)thiazol-2-amine ( 2 ) via Suzuki-Miyaura cross coupling reaction. The chemical structures of 1 and 2 are confirmed using 1 HNMR, 13 CNMR, FT-IR, UV–Vis and single crystal x-ray studies. The XRD study reveals that the both solid state structures ( 1 ) and ( 2 ) are diffused to form poly chain structures due to presence of intra molecular hydrogen bonding (H.B). Furthermore, these compounds were analysed by density functional theory (DFT) at M06-2X/6-311G(d,p), B3LYP/6-31G(d) B3LYP/6-31G(d,p) and B3LYP/6-311G(2d,p) level of theories to obtain optimized geometry, electronic and spectroscopic properties. DFT optimized geometry supports the experimental XRD parameters. Natural bond orbital (NBO) calculation predicted the hyper conjugative interaction and hydrogen bonding in all derivatives. The FT-IR and thermodynamic studies also confirm the presence of hydrogen bonding network in the dimers which agrees well with the XRD results. Moreover, UV–Vis analysis reveals that maximum excitations take place in 1 and 2 due to HOMO → LUMO(98%) and HOMO → LUMO(97%) respectively which show good agreement to experimental data. The first order hyperpolarizability of both molecules is remarkably greater than the value of urea. The global reactivity parameters which are obtained by frontier molecular orbitals disclose that the molecules might be bioactive. [ABSTRACT FROM AUTHOR]

5-Lipoxygenase (5-LO, EC1.13.11.34) has been implicated in the pathogenesis of inflammatory and immune diseases. Recently, aminothiazole comprising inhibitors have been discovered for this valuable target. Yet, the molecular mode of action of this class of substances is only poorly understood. Here, we present the detailed molecular mechanism of action of the compound class and the in vitro pharmacological profile of two lead compounds ST-1853 and ST-1906. Mechanistic studies with recombinant proteins as well as intact cell assays enabled us to define this class as a novel type of 5-LO inhibitors with unique characteristics. The parent compounds herein presented a certain reactivity concerning oxidation and thiol binding: Unsubstituted aminophenols bound covalently to C159 and C418 of human 5-LO. Yet, dimethyl substitution of the aminophenol prevented this reactivity and slowed down phase II metabolism. Both ST-1853 and ST-1906 confirmed their lead likeness by retaining their high potency in physiologically relevant 5-LO activity assays, high metabolic stability, high specificity and non-cytotoxicity. [ABSTRACT FROM AUTHOR]

[Display omitted] Based on a hit from a high-throughput screen, a series of phenyltetrazole amides was synthesized and assayed for inhibitory potency against DapE from Haemophilus influenzae (Hi DapE). The inhibitory potency was modest but confirmed, with the most potent analog containing an aminothiazole moiety displaying an IC 50 = 50.2 ± 5.0 μM. Docking reveals a potential binding mode wherein the amide carbonyl bridges both zinc atoms in the active site, and the tetrazole forms key hydrogen bonds with Arg330. [ABSTRACT FROM AUTHOR]

In the title compound, C5H8N4OS, the dihedral angle between the acetohydrazide moiety and the thiazole ring is 80.96 (8)°. In the crystal, molecules are linked by N—H...O and N—H...N hydrogen bonds generating (010) sheets.

Overexpression of P-glycoprotein (P-gp) plays a key role in the development of multidrug resistance (MDR), the major reason for the failure of chemotherapy in clinics. Ocotillol and its derivatives had been reported with good P-gp-mediated tumor MDR reversal activity in vitro. Herein, a series of ocotillol derivatives fused with 2-aminothiazole (2-AT) via A-ring were designed and synthesized to further improve the tumor MDR reversal potency. These compounds were evaluated for their MDR reversal activity against the KBV cells by MTT assay. Among them, the most promising derivative against P-gp-mediated MDR was compound 12 with 2-AT and glycine in the A-ring. Rhodamine123 (Rh123) accumulation assay, Western blot assay, and P-gp-Glo™ assay showed that compound 12 efficiently inhibited the efflux function of P-gp by stimulating P-gp ATPase rather than downregulating its expression. Moreover, compound 12 sensitized KBV cells to paclitaxel arrested cells in the G 2 /M phase and induced cell apoptosis. Importantly, compound 12 significantly inhibited the growth of KBV cell-derived xenograft tumors in nude mice by increasing the sensitivity of paclitaxel in vivo. Finally, the structure-activity relationships (SARs) of ocotillol derivatives were further investigated. In summary, compound 12 has the potential to overcome MDR in cancer caused by P-gp. [Display omitted] • 24 novel steroid derivatives were synthesized. • Compound 12 enhanced the sensitivity of KBV cells to paclitaxel, vincristine, and mitoxantrone. • Compound 12 enhanced the efficacy of paclitaxel against KBV cancer cell-derived xenograft tumors. • Compound 12 effectively inhibited the efflux function of P-gp. [ABSTRACT FROM AUTHOR]

A series of new potentially multi-targeting antimicrobial 2-aminothiazolyl quinolones were designed, synthesized and characterized by 1 H NMR, 13 C NMR, IR, MS and HRMS spectra. Bioactive assay manifested that some of the prepared compounds showed moderate to good antibacterial and antifungal activities. Noticeably, compound 10f could effectively inhibit the growth of B. typhi and MRSA with MIC values of 1 and 8 μg/mL, respectively. Experimental results revealed that compound 10f was membrane-active and had the ability to rapidly kill the tested strains and effectively prevent the development of bacterial resistance. Moreover, this compound also exhibited low toxicity against L929 cells. Molecular docking indicated that compound 10f could bind with topoisomerase IV–DNA complexes through hydrogen bonds and hydrophobic interactions. Quantum chemical studies were also performed on 10f to understand the structural features essential for activity. The preliminary mechanism research suggested that compound 10f could intercalate into calf thymus DNA to form a steady supramolecular complex which might block DNA replication to exert the powerful bioactivities. [ABSTRACT FROM AUTHOR]

The emergence of antibiotic resistant pathogens is an ongoing main problem in the therapy of bacterial infections. In order to develop promising antitubercular and antibacterial lead compounds, we designed and synthesized a new series of derivatives of 2-aminothiazole conjugated nitrofuran with activities against both Mycobacterium tuberculosis and Staphylococcus aureus . Eight compounds 12e , 12k , 12l , 12m , 18a , 18d , 18e , and 18j emerged as promising antitubercular agents. Structure–activity relationships (SARs) were discussed and showed that the derivatives substituted at the position-3 of benzene of 5-nitro- N -(4-phenylthiazol-2-yl)furan-2-carboxamide exhibited superior potency. The most potent compound 18e , substituted with benzamide at this position, displayed minimum inhibitory concentrations (MICs) of 0.27 μg/mL against Mtb H37Ra and 1.36 μg/mL against S. aureus . Furthermore, compound 18e had no obvious cytotoxicity to normal Vero cells (IC 50 = 50.2 μM). The results suggest that the novel scaffolds of aminothiazole conjugated nitrofuran would be a promising class of potent antitubercular and antimicrobial agents. [ABSTRACT FROM AUTHOR]

Periodontitis is characterized by chronic inflammation and osteoclast-mediated bone loss regulated by the receptor activator of nuclear factor-κB ( RANK), RANK ligand ( RANKL) and osteoprotegerin ( OPG). The aim of this study was to investigate the effect of aminothiazoles targeting prostaglandin E synthase-1 ( mPGES-1) on RANKL- and lipopolysaccharide ( LPS)-mediated osteoclastogenesis and prostaglandin E2 ( PGE2) production in vitro using the osteoclast precursor RAW 264.7 cells. RAW 264.7 cells were treated with RANKL or LPS alone or in combination with the aminothiazoles 4-([4-(2-naphthyl)-1,3-thiazol-2-yl]amino)phenol ( TH-848) or 4-(3-fluoro-4-methoxyphenyl)- N-(4-phenoxyphenyl)-1,3-thiazol-2-amine ( TH-644). Aminothiazoles significantly decreased the number of multinucleated tartrate-resistant acid phosphatase ( TRAP)-positive osteoclast-like cells in cultures of RANKL- and LPS-stimulated RAW 264.7 cells, as well as reduced the production of PGE2 in culture supernatants. LPS-treatment induced mPGES-1 mRNA expression at 16 hrs and the subsequent PGE2 production at 72 hrs. Conversely, RANKL did not affect PGE2 secretion but markedly reduced mPGES-1 at mRNA level. Furthermore, mRNA expression of TRAP and cathepsin K ( CTSK) was reduced by aminothiazoles in RAW 264.7 cells activated by LPS, whereas RANK, OPG or tumour necrosis factor α mRNA expression was not significantly affected. In RANKL-activated RAW 264.7 cells, TH-848 and TH-644 down-regulated CTSK but not TRAP mRNA expression. Moreover, the inhibitory effect of aminothiazoles on PGE2 production was also confirmed in LPS-stimulated human peripheral blood mononuclear cell cultures. In conclusion, the aminothiazoles reduced both LPS- and RANKL-mediated osteoclastogenesis and PGE2 production in RAW 264.7 cells, suggesting these compounds as potential inhibitors for treatment of chronic inflammatory bone resorption, such as periodontitis. [ABSTRACT FROM AUTHOR]

Density functional theory is utilized to elucidate the detailed mechanisms of the reactions between 2-aminooxazole O2 /2-aminothiazole S2 and glyceraldehyde 2 . According to our calculations, in O2 / 2 system, aminooxazoline O3 is formed via two steps including C C formation and cyclization. C C formation determines the reaction diastereoselectivity and ribo-aminooxazoline is the most favorable product. Although oxazole-hemiaminal O6 is not detected in the experiment, it is deduced can be formed theoretically. In S2 / 2 system, aminothiazoline S3 is hard to be generated because of the less nucleophilic ability of S2 . The formation of thiazole-hemiaminal S6 is more favorable than S3 formation in kinetics but somewhat unfavorable in thermodynamics. However, the transformation from S6 to thiazole-aminal S7 is favorable both in kinetics and thermodynamics, which provides a driving force for the formation and transformation of S6 . Additionally, our calculations indicate that phosphate is very important in assisting proton transfer in all of the transformations. [ABSTRACT FROM AUTHOR]