Synthesis and Antiproliferative Potential of Thiazole and 4-Thiazolidinone Containing Motifs as Dual Inhibitors of EGFR and BRAF.

Thiazole and thiazolidinone recur in a wide range of biologically active compounds that reach different targets within the context of tumors and represent a promising starting point to access potential candidates for treating metastatic cancer. Therefore, searching for new lead compounds that show the highest anticancer potency with the fewest adverse effects is a major drug-discovery challenge. Because the thiazole ring is present in dasatinib, which is currently used in anticancer therapy, it is important to highlight the ring.

Synthesis and Structure Determination of Substituted Thiazole Derivatives as EGFR/BRAF Dual Inhibitors Endowed with Antiproliferative Activity.

2,3,4-trisubstituted thiazoles -, having a methyl group in position four, were synthesized by the reaction of 1,4-disubstituted thiosemicarbazides with chloroacetone in ethyl acetate/EtN at room temperature or in ethanol under reflux. The structures of new compounds were determined using NMR spectroscopy, mass spectrometry, and elemental analyses. Moreover, the structure of compound was unambiguously confirmed with X-ray analysis.

Synthesis of bis-thiohydantoin derivatives as an antiproliferative agents targeting EGFR inhibitory pathway.

(R)/(S)-the two enantiomers of 3-substituted-1-[2-(5)-3-substituted-4-benzyl-5-oxo-4-phenyl-2-thioxoimid-azolidin-1-yl]ethyl/propyl-5-benzyl-5-phenyl-2-thioxoimidazolidin-4-ones were formed during the diastereoselective reaction between N,N″-1,ω-alkanediylbis[N'-organylthiourea] derivatives and 2,3-diphenylcyclopropenone in refluxing ethanol. The structures of the isolated compounds were confirmed by NMR, IR, mass spectra and elemental analyses. Moreover, single-crystal X-ray structure analysis was also used to elucidate the structure of the isolated compounds.

Novel quinoline/thiazinan-4-one hybrids; design, synthesis, and molecular docking studies as potential anti-bacterial candidates against MRSA.

In an attempt to develop effective and safe antibacterial agents, we synthesized novel thiazinanones by combining the quinolone scaffold and the 1,3-thiazinan-4-one group by reaction between ((4-hydroxy-2-oxo-1,2-dihydroquinolin-3-yl)methylene)hydrazinecarbothioamides and 2,3-diphenylcycloprop-2-enone in refluxing ethanol in the presence of triethyl amine as a catalyst. The structure of the synthesized compounds was characterized by spectral data and elemental analysis, IR, MS, H and C NMR spectroscopy which showed two doublet signals for CH-5 and CH-6 and four sharp singlets for the protons of thiazinane NH, CH[double bond, length as m-dash]N, quinolone NH and OH, respectively. Also, the C NMR spectrum clearly showed the presence of two quaternary carbon atoms which were assigned to thiazinanone-C-5 and C-6.

Heterocycles from cyclopropenones.

Great attention has been paid to cyclopropenones as they are present in many natural sources. Various synthesized cyclopropenone derivatives also show a wide range of biological activities. The cyclopropenone derivatives undergo a variety of reactions such as ring-opening reactions, isomerization reactions, C-C coupling reactions, C-H activation, cycloaddition reactions, thermal and photo-irradiation reactions, and acid-base-catalyzed reactions under the influence of various chemical reagents (electrophiles, nucleophiles, radicals, and organometallics) and external forces (heat and light).

Autoxidation of 4-Hydrazinylquinolin-2(1)-one; Synthesis of Pyridazino[4,3-:5,6-']diquinoline-6,7(5,8)-diones.

An efficient synthesis of a series of pyridazino[4,3-:5,6-']diquinolines was achieved via the autoxidation of 4-hydrazinylquinolin-2(1)-ones. IR, NMR (H and C), mass spectral data, and elemental analysis were used to fit and elucidate the structures of the newly synthesized compounds. X-ray structure analysis and theoretical calculations unequivocally proved the formation of the structure.

Case Report: Stem cell therapy in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease leading to loss of upper and lower motor neurons at both spinal and bulbar levels.  For patients with ALS rehabilitation is important to maintain functional independence, ensure safety and optimize quality of life but is not curative. Stem cell therapy (SCT) provides a new approach to treat previously incurable diseases although peer reviewed published evidence has shown no benefit in ALS for slowing disease progression or functional loss.

Salivary markers and coronavirus disease 2019: insights from cross-talk between the oral microbiome and pulmonary and systemic low-grade inflammation and implications for vascular complications.

To date, coronavirus disease 2019 (COVID-19) has affected over 6.2 million individuals worldwide, including 1.46 million deaths.

Crystal structure of ()-1-(3-benzyl-5-phenyl-1,3-thia-zol-2-yl-idene)-2-[()-1,2,3,4-tetra-hydro-naphthalen-1-yl-idene]hydrazin-1-ium bromide.

In the title mol-ecular salt, CHNS·Br, the dihedral angles between the thia-zole ring and its attached phenyl and benzoyl rings are 54.81 (7) and 85.51 (7)°, respectively.

Hypoxia-inducible factor (HIF): The link between obesity and COVID-19.

The COVID-19 death toll has involved to date more than 1 million confirmed deaths. The death rate is even higher in the obese COVID-19 patients, as a result of hypoxia, due to the interplay between adipose tissue hypoxia and obstructive sleep apnea. The discrepancy of manifestations seen in COVID-19 seems to be mediated by a differential immune response rather than a differential viral load.

Design and synthesis of hydrazinecarbothioamide sulfones as potential antihyperglycemic agents.

New hydrazinecarbothioamides with a phenylsulfonyl group were synthesized and their structures were identified by different spectroscopic data ( H NMR, C NMR, two-dimensional NMR, mass spectrometry, elemental analysis, and single-crystal X-ray analysis). The mechanism describing the formation of the products was also discussed. The antidiabetic activity of the isolated products was investigated histochemically.

Design, Synthesis, and Molecular Docking of Paracyclophanyl-Thiazole Hybrids as Novel CDK1 Inhibitors and Apoptosis Inducing Anti-Melanoma Agents.

Three new series of paracyclophanyl-dihydronaphtho[2,3-]thiazoles and paracyclophanyl-thiazolium bromides were designed, synthesized, and characterized by their spectroscopic data, along with X-ray analysis. One-dose assay results of anticancer activity indicated that - had the highest ability to inhibit the proliferation of different cancer cell lines. Moreover, the hybrids - were selected for five-dose analyses to demonstrate a broad spectrum of antitumor activity without apparent selectivity.

Chemistry of Substituted Thiazinanes and Their Derivatives.

Thiazinanes and its isomeric forms represent one of the most important heterocyclic compounds, and their derivatives represented a highly potent drug in disease treatment such as, 1,1-dioxido-1,2-thiazinan-1,6-naphthyridine, which has been shown to have anti-HIV activity by a mechanism that should work as anti-AIDS treatment, while ()-methyl 3-(naphthalen-1-ylimino)- 2-thia-4-azaspiro[5 5]undecane-4-carbodithioate showed analgesic activity, cephradine was used as antibiotic and chlormezanone was utilized as anticoagulants. All publications were interested in the chemistry of thiazine (partially or fully unsaturated heterocyclic six-membered ring containing nitrogen and sulfur), but no one was dealing with thiazinane itself which encouraged us to shed new light on these interesting heterocycles. This review was focused on the synthetic approaches of thiazinane derivatives and their chemical reactivity.

Synthesis of 3,3'-methylenebis(4-hydroxyquinolin-2(1H)-ones) of prospective anti-COVID-19 drugs.

During formylation of 2-quinolones by DMF/EtN mixture, the unexpected 3,3'-methylenebis(4-hydroxyquinolin-2(1H)-ones) were formed. The discussed mechanism was proved as due to the formation of 4-formyl-2-quinolone as intermediate. Reaction of the latter compound with the parent quinolone under the same reaction condition gave also the same product.

Synthesis of New Planar-Chiral Linked [2.2]Paracyclophanes--([2.2]-Paracyclophanylcarbamoyl)-4-([2.2]Paracyclophanylcarboxamide, [2.2]Paracyclophanyl-Substituted Triazolthiones and -Substituted Oxadiazoles.

The manuscript describes the synthesis of new racemic and chiral linked paracyclophane assigned as -5-(1,4(1,4)-dibenzenacyclohexaphane-1-yl)carbamoyl)-5'-(1,4(1,4)-dibenzenacyclohexaphane-1-yl)carboxamide. The procedure depends upon the reaction of 5-(1,4(1,4)-dibenzenacyclohexaphane-1-yl)hydrazide with 5-(1,4(1,4)-dibenzenacyclohexaphane-1-yl)isocyanate. To prepare the homochiral linked paracyclophane of a compound, the enantioselectivity of 5-(1,4(1,4)-dibenzenacyclohexaphane-1-yl)carbaldehyde (enantiomeric purity 60% ee), was oxidized to the corresponding acid, which on chlorination, gave the corresponding acid chloride of [2.

New Paracyclophanylthiazoles with Anti-Leukemia Activity: Design, Synthesis, Molecular Docking, and Mechanistic Studies.

A new series of methyl 2-(2-(4'-[2.2]paracyclophanyl)-hydrazinylidene)-3-substituted-4-oxothiazolidin-5-ylidene)acetates - were synthesized from the reaction of paracyclophanyl-acylthiosemicarbazides - with dimethyl acetylenedicarboxylate. Based upon nuclear magnetic resonance (NMR), infrared (IR), and mass spectra (HRMS), the structure of the obtained products was elucidated.

Chemistry and Biological Activities of 1,2,4-Triazolethiones-Antiviral and Anti-Infective Drugs.

Mercapto-substituted 1,2,4-triazoles are very interesting compounds as they play an important role in chemopreventive and chemotherapeutic effects on cancer. In recent decades, literature has been enriched with sulfur- and nitrogen-containing heterocycles which are used as a basic nucleus of different heterocyclic compounds with various biological applications in medicine and also occupy a huge part of natural products. Therefore, we shed, herein, more light on the synthesis of this interesting class and its application as a biologically active moiety.

Regioselective and stereoselective synthesis of epithiomethanoiminoindeno[1,2-b]furan-3-carbonitrile: heterocyclic [3.3.3]propellanes.

Synthesis of heteropropellanes in one step: the reaction between dicyanomethylene-1,3-indanedione (CNIND) and N-substituted-2-(2,4-dinitrophenyl)hydrazinecarbothioamides, furnished (3aR,8bS,Z)-2-amino-9-substituted-10-(2-(2,4-dinitrophenyl)hydrazono)-4-oxo-4H-3a,8b-(epithiomethanoimino)indeno[1,2-b]furan-3-carbonitrile as a type of (2,4-dinitrophenyl)hydrazono[3.3.3]propellanes in good yields as single diastereomers.

Synthesis of New Fused Heterocyclic 2-Quinolones and 3-Alkanonyl-4-Hydroxy-2-Quinolones.

Herein, we report the synthesis of 5,12-dihydropyrazino[2,3-:5,6-']difuro[2,3-:4,5-']-diquinoline-6,14(,12)diones, 2-(4-hydroxy-2-oxo-1,2-dihydroquinolin-3-yl)-1,4-diphenyl- butane-1,4-diones and 4-(benzo-[]oxazol-2-yl)-3-hydroxy-1-[4,5]oxazolo[3,2-]pyridine-1-one. The new candidates were synthesized and identified by different spectroscopic techniques, and X-ray crystallography.

Functionalized 1,3-Thiazolidin-4-Ones from 2-Oxo-Acenaphthoquinylidene- and [2.2]Paracyclophanylidene-Thiosemicarbazones.

The reactions of dialkyl acetylenedicarboxylates with various 2-oxo-acenaphthoquinylidene- and 4-acetyl[2.2]paracyclophanylidene-thiosemicarbazones were investigated. Using simple experimental procedures, 1,3-Thiazolidin-4-ones derived from acenaphthequinone or [2.

Design, synthesis, and DNA interaction studies of furo-imidazo[3.3.3]propellane derivatives: Potential anticancer agents.

A large number of natural products containing the propellane scaffold have been reported to exhibit cytotoxicity against several cancers; however, their mechanism of action is still unknown. Anticancer drugs targeting DNA are mainly composed of small planar molecule/s that can interact with the DNA helix, causing DNA malfunction and cell death. The aim of this study was to design and synthesize propellane derivatives that can act as DNA intercalators and/or groove binders.

Convenient diastereoselective synthesis of annulated 3-substituted-(5S*,6S*,Z)-2-(2-(2,4-dinitrophenyl)hydrazono)-5,6-diphenyl-1,3-thiazinan-4-ones.

Racemic 2-(2,4-dinitrophenyl)hydrazono)-5,6-diphenyl-1,3-thiazinan-4-ones and (Z)-N'-(2,4-dinitrophenyl)-2,3-diphenylacrylohydrazide were formed during the diastereoselective reaction between 4-substituted 1-(2,4-dinitrophenyl)thiosemicarbazides and 2,3-diphenylcycloprop-2-enone under refluxing ethanol. The structures of the synthesized compounds were confirmed by single-crystal X-ray analyses.

Regioselective formation of 1,2,4-triazoles by the reaction of amidrazones in the presence of diethyl azodicarboxylate and catalyzed by triethylamine.

A general method for the synthesis of 1,3,5-trisubstituted 1,2,4-triazoles has been developed from reaction of amidrazones with ethyl azodicarboxylate and triethylamine (Mitsunobu reagent) in EtOH. This highly regioselective one-pot process provides rapid access to highly diverse triazoles. The reaction was explained, based on Mitsunobu reagent oxidizing ethanol to acetaldehyde, which would then react with amidrazones to give the substituted 3-methyltriazoles.

Crystal structure of 3-(prop-2-en-1-yl)-1-{[(1E)-1,2,3,4-tetra-hydro-naphthalen-1-yl-idene]amino}-thio-urea.

In the title compound, C14H17N3S, the dihedral angle between the planes of the benzene ring and the thio-semicarbazone group (r.m.s.