Month: October 2022

Schneider, Tanya L.; Walsh, Christopher T.; O’Connor, Sarah E. published the artcile< Utilization of Alternate Substrates by the First Three Modules of the Epothilone Synthetase Assembly Line>, Product Details of C12H18N2O4S, the main research area is substrate specificity epothilone synthetase Sorangium serine polyketide oxazole analog.

The epothilones, a family of macrolactone natural products produced by the myxobacterial species Sorangium cellulosum, are of current clin. interest as antitumor agents. Inspection of the structure of the epothilones suggests a hybrid polyketide/nonribosomal peptide biosynthetic origin, and the recent sequencing of the epothilone biosynthetic gene cluster has validated this proposal. Here we have examined unnatural substrates with the first two enzymes of the biosynthetic pathway, EpoA and EpoB, to investigate the enzymic construction of alternate heterocyclic structures and the subsequent elongation of these products by the third enzyme of the pathway, EpoC. The epothilone biosynthetic machinery can utilize serine to install an oxazole in place of a thiazole in the epothilone structure and will tolerate functionalized donor groups from the EpoA-ACP domain to produce epothilone fragments modified at the C21 position. These studies with the early enzymes of the epothilone biosynthesis cluster suggest that combinatorial biosynthesis may be a viable means for producing a variety of epothilone analogs that incorporate diversity into the heterocycle starter unit.

Journal of the American Chemical Society published new progress about Sorangium cellulosum. 96929-05-4 belongs to class thiazole, and the molecular formula is C12H18N2O4S, Product Details of C12H18N2O4S.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Hitchin, James R.; Blagg, Julian; Burke, Rosemary; Burns, Samantha; Cockerill, Mark J.; Fairweather, Emma E.; Hutton, Colin; Jordan, Allan M.; McAndrew, Craig; Mirza, Amin; Mould, Daniel; Thomson, Graeme J.; Waddell, Ian; Ogilvie, Donald J. published the artcile< Development and evaluation of selective, reversible LSD1 inhibitors derived from fragments>, Quality Control of 57493-24-0, the main research area is LSD1 inhibitor SAR anticancer acute myeloid leukemia MAOA protein.

Two series of aminothiazoles have been developed as reversible inhibitors of lysine specific demethylase 1 (LSD1) through the expansion of a hit derived from a high concentration biochem. fragment based screen of 2466 compounds The potency of the initial fragment hit was increased 32-fold through synthesis, with one series of compounds showing clear structure-activity relationships and inhibitory activities in the range of 7 to 187 μM in a biochem. assay. This series also showed selectivity against the related FAD-dependent enzyme mono-amine oxidase A (MAO-A). Although a wide range of irreversible inhibitors of LSD1 have been reported with activities in the low nanomolar range, this work represents one of the first reported examples of a reversible small mol. inhibitor of LSD1 with clear SAR and selectivity against MAO-A, and could provide a platform for the development of more potent reversible inhibitors. Herein, we also report the use of a recently developed cell-based assay for profiling LSD1 inhibitors, and present results on our own compounds as well as a selection of recently described reversible LSD1 inhibitors.

MedChemComm published new progress about Acute myeloid leukemia. 57493-24-0 belongs to class thiazole, and the molecular formula is C9H7N3O2S, Quality Control of 57493-24-0.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Chen, Tzu-Yin; Chen, Mei-Ru; Liu, Shan-Wen; Lin, Jin-Yan; Yang, Ya-Ting; Huang, Hsin-Ying; Chen, Jen-Kun; Yang, Chung-Shi; Lin, Kurt Ming-Chao published the artcile< Assessment of polyethylene glycol-coated gold nanoparticle toxicity and inflammation in vivo using NF-κB reporter mice>, Recommanded Product: (S)-2-(6-Hydroxybenzo[d]thiazol-2-yl)-4,5-dihydrothiazole-4-carboxylic acid, the main research area is polyethylene glycol coated gold nanoparticle toxicity inflammation reporter mice; NF-κB; PEG surface modification; gold nanoparticle; liver inflammation; reporter imaging; steatosis.

Polyethylene glycol (PEG) coating of gold nanoparticles (AuNPs) improves AuNP distribution via blood circulation. The use of PEG-coated AuNPs was shown to result in acute injuries to the liver, kidney, and spleen, but long-term toxicity has not been well studied. In this study, we investigated reporter induction for up to 90 days in NF-κB transgenic reporter mice following i.v. injection of PEG-coated AuNPs. The results of different doses (1 and 4μg AuNPs per g of body weight), particle sizes (13 nm and 30 nm), and PEG surfaces (methoxyl- or carboxymethyl-PEG 5 kDa) were compared. The data showed up to 7-fold NF-κB reporter induction in mouse liver from 3 h to 7 d post PEG-AuNP injection compared to saline-injected control mice, and gradual reduction to a level similar to control by 90 days. Agglomerates of PEG-AuNPs were detected in liver Kupffer cells, but neither gross pathol. abnormality in liver sections nor increased activity of liver enzymes were found at 90 days. Injection of PEG-AuNPs led to an increase in collagen in liver sections and elevated total serum cholesterol, although still within the normal range, suggesting that inflammation resulted in mild fibrosis and affected hepatic function. Administrating PEG-AuNPs inevitably results in nanoparticles entrapped in the liver; thus, further investigation is required to fully assess the long-term impacts by PEG-AuNPs on liver health.

International Journal of Molecular Sciences published new progress about Hepatotoxicity. 2591-17-5 belongs to class thiazole, and the molecular formula is C11H8N2O3S2, Recommanded Product: (S)-2-(6-Hydroxybenzo[d]thiazol-2-yl)-4,5-dihydrothiazole-4-carboxylic acid.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Ingram, Nicola; McVeigh, Laura E.; Abou-Saleh, Radwa H.; Maynard, Juliana; Peyman, Sally A.; McLaughlan, James R.; Fairclough, Michael; Marston, Gemma; Valleley, Elizabeth M. A.; Jimenez-Macias, Jorge L.; Charalambous, Antonia; Townley, William; Haddrick, Malcolm; Wierzbicki, Antonia; Wright, Alexander; Volpato, Milene; Simpson, Peter B.; Treanor, Darren E.; Thomson, Neil H.; Loadman, Paul M.; Bushby, Richard J.; Johnson, Benjamin R. G.; Jones, Pamela F.; Evans, J. Anthony; Freear, Steven; Markham, Alexander F.; Evans, Stephen D.; Coletta, P. Louise published the artcile< Ultrasound-triggered therapeutic microbubbles enhance the efficacy of cytotoxic drugs by increasing circulation and tumor drug accumulation and limiting bioavailability and toxicity in normal tissues>, Recommanded Product: (S)-2-(6-Hydroxybenzo[d]thiazol-2-yl)-4,5-dihydrothiazole-4-carboxylic acid, the main research area is VEGFR2 SN38 liposome drug delivery circulation bioavailability colorectal cancer; Microbubble; VEGFR2; colorectal cancer; nanoformulation; ultrasound.

Most cancer patients receive chemotherapy at some stage of their treatment which makes improving the efficacy of cytotoxic drugs an ongoing and important goal. Despite large numbers of potent anti-cancer agents being developed, a major obstacle to clin. translation remains the inability to deliver therapeutic doses to a tumor without causing intolerable side effects. To address this problem, there has been intense interest in nanoformulations and targeted delivery to improve cancer outcomes. The aim of this work was to demonstrate how vascular endothelial growth factor receptor 2 (VEGFR2)-targeted, ultrasound-triggered delivery with therapeutic microbubbles (thMBs) could improve the therapeutic range of cytotoxic drugs. Methods: Using a microfluidic microbubble production platform, we generated thMBs comprising VEGFR2-targeted microbubbles with attached liposomal payloads for localised ultrasound-triggered delivery of irinotecan and SN38 in mouse models of colorectal cancer. I.v. injection into tumor-bearing mice was used to examine targeting efficiency and tumor pharmacodynamics. High-frequency ultrasound and bioluminescent imaging were used to visualise microbubbles in real-time. Tandem mass spectrometry (LC-MS/MS) was used to quantitate intratumoral drug delivery and tissue biodistribution. Finally, 89Zr PET radiotracing was used to compare biodistribution and tumor accumulation of ultrasound-triggered SN38 thMBs with VEGFR2-targeted SN38 liposomes alone. Results: ThMBs specifically bound VEGFR2 in vitro and significantly improved tumor responses to low dose irinotecan and SN38 in human colorectal cancer xenografts. An ultrasound trigger was essential to achieve the selective effects of thMBs as without it, thMBs failed to extend intratumoral drug delivery or demonstrate enhanced tumor responses. Sensitive LC-MS/MS quantification of drugs and their metabolites demonstrated that thMBs extended drug exposure in tumors but limited exposure in healthy tissues, not exposed to ultrasound, by persistent encapsulation of drug prior to elimination. 89Zr PET radiotracing showed that the percentage injected dose in tumors achieved with thMBs was twice that of VEGFR2-targeted SN38 liposomes alone. Conclusions: thMBs provide a generic platform for the targeted, ultrasound-triggered delivery of cytotoxic drugs by enhancing tumor responses to low dose drug delivery via combined effects on circulation, tumor drug accumulation and exposure and altered metabolism in normal tissues.

Theranostics published new progress about Bioavailability. 2591-17-5 belongs to class thiazole, and the molecular formula is C11H8N2O3S2, Recommanded Product: (S)-2-(6-Hydroxybenzo[d]thiazol-2-yl)-4,5-dihydrothiazole-4-carboxylic acid.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Sharma, G. M.; Parshad, Baldev; Narang, K. S. published the artcile< Thiazole derivatives. VI. Synthesis of 2-chloro-5-bromothiazoles>, Safety of 5-Bromo-2-chlorothiazole, the main research area is chloro bromo thiazoles; bromo chloro thiazoles; thiazoles chloro bromo.

The title compounds (I) were prepared as follows: ω – thiocyano ketones, NCSCH2C:OR were dissolved in CCl4 or C6H6, depending upon their solubilities, equivalent amounts C5H5N added, and an equivalent amount Br in the same solvent added dropwise at 40-50°. The solvent was distilled in vacuo, the residue treated with H2O to remove C5H5N.HBr, the ω-bromo-ω-thiocyano ketones RCOCH2SCN (II) were collected, washed, and crystallized from EtOH, solutions of II in dry ether saturated with dry HCl gas at 0°, the mixtures kept 12 hrs. at room temperature, the ether was decanted, and the residue purified either by distillation or crystallization to afford 2-chloro-5-bromothiazoles (III). The following II and III were prepared [R, m.p. II, % yield II, m.p. (or b.p./mm.) III, and % yield given]: Ph, 74°, 55.5, (155°/7), 67.6; p-MeC6H4, 94°, 54.5, 64°, 66.03; p-MeOC6H4, 81°, 86.2, 96°, 69.8; p-ClC6H4, 136°, 67.8, 85°, 70.9; p-BrC6H4, 120°, 71.6, 108°, 66.7.

Indian Journal of Chemistry published new progress about Cyclization. 3034-56-8 belongs to class thiazole, and the molecular formula is C3HBrClNS, Safety of 5-Bromo-2-chlorothiazole.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Hafez, Ebtissam Abdel Aziz; Abed, Nosrat Mustafa; Elsakka, Ibrahim Ahmed; Elnagdi, Mohamed Hilmy published the artcile< Reactions with heterocyclic diazonium salts. Synthesis of several new azolylhydrazones>, Reference of 72054-60-5, the main research area is azolylhydrazone preparation cyclization; fused azole; thiazolylhydrazone; triazolylhydrazone; thiazolotriazine; pyrazolotriazine.

Several new stable azolylhydrazones, e.g. I and II, were synthesized via coupling of diazotized cyclic amidines with active methylene reagents. The obtained compounds were utilized for synthesis of several, otherwise not readily accessible fused azoles, e.g. III and IV.

Journal of Heterocyclic Chemistry published new progress about Cyclocondensation reaction. 72054-60-5 belongs to class thiazole, and the molecular formula is C7H10N2O2S, Reference of 72054-60-5.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Sieng, Bora; Maldonado, Matias Funes; Romagnoli, Carlo; Amedjkouh, Mohamed published the artcile< One-Pot Alkynylation of Azaaryl Aldehydes and Spontaneous Base-Free Rearrangement into Enone Esters: an Autoinductive Mechanism>, Formula: C4H3NOS, the main research area is unsaturated ketoester diastereoselective preparation; butyllithium methylzinc catalyst addition propiolate heteroaryl aldehyde stereoselective rearrangement; isotope labeling allenoate trapping mechanism addition rearrangement propargylic alc.

When heteroaromatic aldehydes are reacted with Et propiolate in the presence of Me2Zn or BuLi, γ-oxo-α,β-unsaturated esters were generated by spontaneous rearrangements of the intermediate propargylic alcs.; in some cases, the propargyl alcs. were formed without rearrangement. The mechanism of the rearrangement was studied using isotope labeling and trapping of a proposed allenoate intermediate; an autocatalytic mechanism is proposed.

European Journal of Organic Chemistry published new progress about Addition reaction. 1003-32-3 belongs to class thiazole, and the molecular formula is C4H3NOS, Formula: C4H3NOS.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Kharidia, S. P.; Trivedi, J. J. published the artcile< Synthesis of 3-(substituted benzyl)-5-alkylrhodanines>, Related Products of 10574-69-3, the main research area is .

Preparation of benzylamines and benzylammonium dithiocarbamates (not isolated) and their condensation with α-halo fatty acids were carried out according to Raval and T. (CA 57, 12465h) to give the tabulated I (m.ps. shown). I showed no antifungal, antibacterial, or antiprotozoal activity.

Journal of the Indian Chemical Society published new progress about 10574-69-3. 10574-69-3 belongs to class thiazole, and the molecular formula is C10H9NOS2, Related Products of 10574-69-3.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Ribeiro, Gabriel H.; Guedes, Adriana P. M.; de Oliveira, Tamires D.; de Correia, Camila R. S. T. b.; Colina-Vegas, Legna; Lima, Mauro A.; Nobrega, Joaquim A.; Cominetti, Marcia R.; Rocha, Fillipe V.; Ferreira, Antonio G.; Castellano, Eduardo E.; Teixeira, Felipe R.; Batista, Alzir A. published the artcile< Ruthenium(II) Phosphine/Mercapto Complexes: Their in Vitro Cytotoxicity Evaluation and Actions as Inhibitors of Topoisomerase and Proteasome Acting as Possible Triggers of Cell Death Induction>, Application In Synthesis of 96-53-7, the main research area is preparation ruthenium diphenylphosphinobutane phosphine diphenylpyridylphosphine thiazolinethiol complex; crystal structure ruthenium diphenylphosphinobutane phosphine diphenylpyridylphosphine thiazolinethiol complex; HSA interaction ruthenium diphenylphosphinobutane phosphine diphenylpyridylphosphine thiazolinethiol complex; cyclic voltammetry ruthenium diphenylphosphinobutane phosphine diphenylpyridylphosphine thiazolinethiol complex; DNA interaction ruthenium diphenylphosphinobutane phosphine diphenylpyridylphosphine thiazolinethiol complex; anticancer activity ruthenium diphenylphosphinobutane phosphine diphenylpyridylphosphine thiazolinethiol complex.

A series of new ruthenium complexes of the general formula [Ru(NS)(dpphpy)(dppb)]PF6 (Ru1-Ru3), where dpphpy = diphenyl-2-pyridylphosphine, NS ligands = 2-thiazoline-2-thiol (tzdt, Ru1, 1), 2-mercaptopyrimidine (pySm, Ru2, 2), and 4,6-diamino-2-mercaptopyrimidine (damp, Ru3, 3), and dppb = 1,4-bis(diphenylphosphino)butane, were synthesized and characterized by elemental anal., spectroscopic techniques (IR, UV/visible, and 1D and 2D NMR), and x-ray diffraction. In the characterization, the correlation between the phosphorus atoms and their resp. aromatic hydrogen atoms of the compounds in the assignment stands outs, by 1H-31P HMBC experiments The compounds show anticancer activities against A549 (lung) and MDA-MB-231 (breast) cancer cell lines, higher than the clin. drug cisplatin. All of the complexes are more cytotoxic against the cancer cell lines than against the MRC-5 (lung) and MCF-10 Å (breast) nontumorigenic human cell lines. For A549 tumor cells, cell cycle anal. upon treatment with Ru2 showed that it inhibits the mitotic phase because arrest was observed in the Sub-G1 phase. Addnl., the compound induces cell death by an apoptotic pathway in a dose-dependent manner, according to annexin V-PE assay. The multitargeted character of the compounds was studied, and the biomols. were DNA, topoisomerase IB, and proteasome, as well as the fundamental biomol. in the pharmacokinetics of drugs, human serum albumin. The complexes do not target DNA in the cells. At low concentrations, the compounds showed the ability to partially inhibit the catalytic activity of topoisomerase IB in the process of relaxation of the DNA plasmid. Among the complexes assayed in cultured cells, complex Ru3 was able to diminish the proteasomal chymotrypsin-like activity to a greater extent. New ruthenium phosphine complexes show anticancer activities against A549 (lung) and MDA-MB-231 (breast) cancer cell lines, higher than the clin. drug cisplatin. For A549 tumor cells, cell cycle anal. upon treatment with Ru2 showed that it inhibits the mitotic phase because arrest was observed in the Sub-G1 phase and induces cell death by an apoptotic pathway. The multitargeted character of the compounds was studied with the biomols. DNA, topoisomerase IB, and proteasome.

Inorganic Chemistry published new progress about Antitumor agents. 96-53-7 belongs to class thiazole, and the molecular formula is C3H5NS2, Application In Synthesis of 96-53-7.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Martinez, Ana; Alonso, Mercedes; Castro, Ana; Dorronsoro, Isabel; Gelpi, J. Luis; Luque, F. Javier; Perez, Concepcion; Moreno, Francisco J. published the artcile< SAR and 3D-QSAR Studies on Thiadiazolidinone Derivatives: Exploration of Structural Requirements for Glycogen Synthase Kinase 3 Inhibitors>, Safety of 3-Benzyl-2-thioxothiazolidin-4-one, the main research area is thiadiazolidinone derivative preparation QSAR glycogen synthase kinase 3 inhibitor.

The 2,4-disubstituted thiadiazolidinones (TDZD) are described as the first ATP-noncompetitive GSK-3 inhibitors. Following an SAR study about TDZD, different structural modifications in the heterocyclic ring aimed to test the influence of each heteroatom on the biol. study are here reported here. Various compounds such as hydantoins, dithiazolidindiones, rhodanines, maleimides, and triazoles were synthesized and screened as GSK-3 inhibitors. After an extensive SAR study among these different heterocyclic families, TDZDs have been revealed as a privileged scaffold for the selective inhibition of GSK-3. A Co-MFA anal. was also performed highlighting the mol. electrostatic field interaction in the interaction of TDZDs with GSK-3. Moreover, first mapping studies indicate two binding modes which in turn might imply relevant differences in the mechanism that underly the inhibitory activity of TDZDs.

Journal of Medicinal Chemistry published new progress about Conformation. 10574-69-3 belongs to class thiazole, and the molecular formula is C10H9NOS2, Safety of 3-Benzyl-2-thioxothiazolidin-4-one.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica