Thiazine Derivatives Research Articles

Green Synthetic Methods of Oxazine and Thiazine Scaffolds as Promising Medicinal Compounds: A Mini-review.

Medical researchers have paid close attention to the green synthesis of oxazine and thiazine derivatives since they provided a lead molecule for the creation of numerous possible bioactive compounds. This review provides more information on green synthesis, which will be very helpful to researchers in creating the most effective, affordable, and clinically significant thiazine and oxazine derivatives that are anticipated to have strong pharmacological effects. This has resulted in the identification of several substances with a wide range of intriguing biological functions. This article's goal is to examine the numerous green chemical processes used to create oxazine and thiazine derivatives and their biological activity. We anticipate that researchers interested in oxazine and thiazine chemicals will find this material to be useful. We anticipate that medicinal chemists looking for new active medicinal components for drug discovery and advance progress will find this review of considerable interest.

Fabrication of stannous sulfide nanoparticles for photodegradation of thiazine derivative and evaluation of its antibacterial activity

The photocatalytic degradation of environmentally harmful chemicals has been extensively explored using a variety of photocatalysts and approaches. However, achieving efficient decomposition and removal of persistent contaminants from the aquatic environment remains a challenging factor. In this study, we report stannous sulfide nanoparticles (SnS2 NPs) prepared by a simple hydrothermal technique and characterized using various analytical methods. The prepared SnS2 NPs were used for the degradation of Methylene Blue (MB) dye under visible light irradiation, which resulted in outstanding degradation compared to other photocatalysts. According to our results, the SnS2 NPs can destroy 98.4 % of MB dye (10 ppm) in 60 minutes effectively, owing to a narrowed band energy gap and photo-induced carrier separation. Based on the results of free-radical scavenging experiment, we confirmed that hydroxyl radicals (•OH) are the key reactive species, and on this basis elucidated the possible degradation mechanism. Moreover, the SnS2 NPs photocatalyst exhibited good stability in degrading MB even after four recycles. Additionally, we analyzed the antibacterial activity of the prepared SnS2 NPs against pathogenic bacteria. As a result of this research, the proposed photocatalyst shows high potential for environmental remediation of harmful contaminants.

Investigating Solvent-Induced Changes in Structure and Nonlinear Optical Behavior of Thiazine Derivatives

In this study, we examine the effects of solvent media on the structural and optical behaviors of two isomers of thiazine derivatives: rac-2-(4-nitrophenyl)-3-phenyl-2,3,5,6-tetrahydro4H-1,3-thiazin-4-one and (2S)-2-(3-nitrophenyl)-3-phenyl-2,3,5,6-tetrahydro-4H-1,3-thiazin4-one. The solvent effects were modeled using the polarizable continuum model through density functional theory. Electrical parameters for rac-2-(4-nitrophenyl)-3-phenyl-2,3,5,6-tetrahydro4H-1,3-thiazin-4-one and (2S)-2-(3-nitrophenyl)-3-phenyl-2,3,5,6-tetrahydro-4H-1,3-thiazin-4-one were determined using the density functional theory at the CAM-B3LYP/6-311+G(d) level. We studied the influence of isomer structures in various solvent media on the Hyper-RayleighScattering first hyperpolarizability, considering both static and dynamic scenarios. This research particularly emphasizes the implications of relocating the NO2 group from the meta-position (2S)-2-(3-nitrophenyl)-3-phenyl-2,3,5,6-tetrahydro-4H-1,3-thiazin-4-one to the para-position rac-2-(4-nitrophenyl)-3-phenyl-2,3,5,6-tetrahydro-4H-1,3-thiazin-4-one on molecular geometries, linear and nonlinear optical parameters, and gap energies across different solvent media. Bond dissociation energy calculations for hydrogen atoms and all other single acyclic bonds were performed for both derivatives to assess degradation and autoxidation properties. Additional insights from non-bonding orbitals, molecular electrostatic surface potential, Fukui calculations, electron localization function, and localized orbital locator are detailed.

Design, enantioselective synthesis, and antiviral activities against potato virus Y of axially chiral thiazine derivatives

AbstractA series of novel thiazine derivatives featuring axial chirality in both (R) and (S) configurations were successfully synthesized by N‐heterocyclic carbene (NHC)‐catalyzed enantioselective [3 + 3] annulations, and their potential as anti‐plant virus agents against potato virus Y (PVY) was evaluated. Biological activity results demonstrated that most of these chiral thiazine derivatives exhibited significant activities against PVY. Notably, compound (S)‐3g displayed a remarkable 58% inactivation effect against PVY at a concentration of 500 μg/mL, slightly surpassing the effectiveness of Ningnanmycin (NNM) at 57%. Additionally, (S)‐3g exhibited curative activity of 57%, which is superior to NNM (53%). Molecular docking studies revealed preliminary insights into the distinct biological properties of the two different enantiomers, (R) or (S)‐3g against PVY, wherein single enantiomer (S)‐3g formed a more stable interaction with PVY‐CP, as indicated by its lower binding free energy (−41.18 kcal/mol) compared to (R)‐3g (−36.9 kcal/mol). The findings in this study with a new class of axially chiral thiazine derivatives shall inspire further development of chiral heterocycles as potential drug candidates for the protection of plant virus infections.

Various Synthetic Methods and Diverse Therapeutic Potential of Substituted Thiazine Derivatives

Abstract: Heterocyclic compounds are currently of great interest in pharmaceutical research. Many natural products, including vitamins, hormones, and antibiotics, contain heterocyclic compounds, and these substances have grown in importance. Heterocyclic thiazine derivatives have numerous pharmacological actions, including anticancer, antimicrobial, antipsychotic, anti-mycobacterial, anti-fungal, antiviral, antimycobacterial, antioxidant, analgesic, antipyretic, anti-inflammatory activities, which is present in numerous substances. The N-CS linkage in its scaffold and the ease and economy of its synthesis methods have been key factors in the development of these molecules. Recently, numerous studies considering the various biological actions of thiazines have been published. Thiazine, a six-membered heterocyclic compound with nitrogen and sulfur in its ring system, has a wide range of chemical possibilities, which has encouraged insistent research into their various synthesis processes. The current review focuses on thiazine derivatives with potential biological activities.

Synthesis of heterocyclic and study activities in agriculture as anti-dubas on date palm trees via cholinesterase inhibitors

Thiazine derivatives, particularly chalcones, have garnered attention owing to their broad agricultural applications. This study aimed to synthesize chalcone derivatives and evaluate their insecticidal efficacy against Dubas bugs on date palm trees. In this study, we synthesized chalcone derivatives (A and B) via the condensation of p-substituted acetophenone and terephthalaldehyde in a basic medium. The compounds were characterized using 1H-NMR and FT-IR spectroscopy and evaluated for their insecticidal activity against Dubas bugs affecting date palm trees. Compound C, synthesized at a concentration of 7000 ppm, exhibited the highest efficacy in reducing dubas populations within the shortest time. Molecular studies revealed that all synthesized derivatives inhibited acetylcholinesterase (AChE), as confirmed by their interaction with the crystallographic structure of AChE (PDB ID:6xyu).

Simultaneous diversity-oriented synthesis of diverse benzo[d][1,3]thiazine libraries from identical substrates

Using o-isothiocyanato-(E)-cinnamaldehydes as powerful and versatile precursors, a facile domino reaction for the simultaneous formation of a compound library similar to natural products 3,4-dihydroquinazoline derivatives and 2,4-dihydro-1H-benzo[d][1,3]thiazine derivatives has been developed. The domino reaction of o-isothiocyanato-(E)-cinnamaldehydes with hydroxylamine resulted in the simultaneous formation of N/S-heterocycles and N/N-heterocycles, generating six classes of previously unknown 2,4-dihydro-1H-benzo[d][1,3]thiazine derivatives with various functional groups. This strategy is a typical example of diversity-oriented synthesis method.

Nematicidal Characterization of Newly Synthesized Thiazine Derivatives Using Caenorhabditis elegans as the Model Organism.

In humans, animals, and agriculture, parasitic nematode infection is a very serious issue. Many drugs are being used to control nematode infections. Owing to toxicity and nematodes' resistance to the available drugs, special attention is required to synthesize new drugs that are environmentally friendly with high-level efficacy. In the present study, various substituted thiazine derivatives (1 to 15) were synthesized, and the structures were confirmed by infrared, proton (1H), and 13C NMR spectroscopies. The nematicidal potential of the synthesized derivatives was characterized using Caenorhabditis elegans (C. elegans) as a model organism. Among all synthesized compounds, 13 (LD50 = 38.95 μg/mL) and 15 (LD50 = 38.21 μg/mL) were considered the most potent compounds. Most compounds showed excellent anti-egg-hatching activity. Fluorescence microscopy confirmed that compounds 4, 8, 9, 13, and 15 displayed a high apoptotic effect. The expressions of gst-4, hsp-4, hsp16.2, and gpdh-1 genes were high in affected (treated with thiazine derivatives) C. elegans in comparison with normal C. elegans. The present research revealed that modified compounds are highly effective as they showed the gene level changes in the selected nematode. Due to structural modification in thiazine analogues, the compounds showed various modes of action. The most effective thiazine derivatives could be excellent candidates for novel broad-scale nematicidal drugs.

Synthesis of Heterocyclic Compounds Via Chalcone Derivatives and Study Activity of Some these Compounds as Pesticides (Anti-Dubas)

In this research, we synthesized oxazine and thiazine derivatives (3-6). These derivatives of chacone compounds (1 and 2) that synthesized from 4- hydroxyacetophenone and aldehyde derivatives such as, 4-bromobenzaldehyde and 4- chlorobenzaldehyde. These derivatives of chalcone (1-2) reacted with urea to produce oxazine derivatives as 4-[4-amino-6-(4-subsutitedphenyl)-2H-1,3-oxazin-2-yl] phenol (3 and 4) and thiourea to produce 4-[4-amino-6-(4-subsutitedphenyl)-2H-1,3-thiazin-2-yl] phenol (5 and 6). These derivatives were characterization by spectroscopy methods such as, FTIR and 1HNMR. Some compounds (3 and 5) that synthesized tested as Pesticides (anti-dubas) through the spray method and these derivatives killed Dubas and we noted the compound 5 was more active from compound 3 because compound 5 have been S atom in his structure that bonded in active group in dubas by effect on Cholinesterase enzyme in the insect.

Carbene-Catalyzed Atroposelective Annulation for Quick Access to Axially Chiral Thiazine Derivatives.

An N-heterocyclic carbene (NHC)-catalyzed atroposelective annulation reaction is disclosed for quick and efficient access to thiazine derivatives. A series of axially chiral thiazine derivatives bearing various substituents and substitution patterns were produced in moderate to high yields with moderate to excellent optical purities. Preliminary studies revealed that some of our products exhibit promising antibacterial activities against Xanthomonas oryzae pv. oryzae (Xoo) that causes rice bacterial blight.

Difluorocarbene-Triggered [1+5] Annulation: Access to Functionalized 1,1-Difluoro-1,9a-dihydropyrido[2,1-c][1,4]thiazine Derivatives

Difluorocarbene-triggered [1+5] annulation is developed to access 1,1-difluoro-1,9a-dihydropyrido[2,1-c][1,4]thiazine-3,4-dicarboxylate derivatives in satisfactory to good yields via the direct reaction of potassium bromodifluoroacetate and pyridinium 1,4-zwitterionic thiolates under heating. Pyridinium 1,4-zwitterionic thiolates first nucleophilically attack difluorocarbene generated from potassium bromodifluoroacetate followed by an intramolecular nucleophilic addition to pyridiniums. This method provides an expeditious route to introduce the difluoromethyl group into the 1,9a-dihydropyrido[2,1-c][1,4]thiazine ring, even to modify drug molecules.

Direct and safe one-pot synthesis of functionalized dimethyl 1-aryl-1,9a-dihydropyrido[2,1-c][1,4]thiazine-1-phosphonates

A visible-light-induced direct and safe synthesis of functionalized dimethyl 1-aryl-1,9a-dihydropyrido[2,1-c][1,4]thiazine-1-phosphonates is realized from dimethyl (aryl(2-tosylhydrazono)methyl)phosphonates and pyridinium 1,4-zwitterionic thiolates with cesium carbonate as base in dichloromethane. The reaction involves the carbene generation from dimethyl (aryl(2-tosylhydrazono)methyl)phosphonates in the presence of cesium carbonate as base and the [1+5] annulation of the carbenes with pyridinium 1,4-zwitterionic thiolates to synthesize functionalized 1,9a-dihydropyrido[2,1-c][1,4]thiazine derivatives. The method avoids preparing, storing, and using potentially dangerous phosphoryl diazo compounds and features simple, convenient, catalyst-free, and mild reaction conditions.

Synthesis, characterisation and biological activities of N-phenyl-ethan-1-one-2,4-dimethyl-1,3-butadiene-1,4-thiazin derivatives

A facile synthesis of some new 1, 2- thiazine derivatives by the Claisen-Schmidt reaction-induced aldolic condensation of enolizable aromatic ketones with substituted benzaldehydes, and then they were treated with urea and thiourea to obtain the corresponding pyrimidine derivatives. IR, 1H and 13C-NMR spectroscopy were used to analyze all produced substances. The synthesized compounds (5, 9-11 and 14-15) were screened for their biological activity against two species of bacteria and fungi according to the gram stain, and all compounds indicated growth inhibition against Escherichia coli, Staphylococcus aureus, and fungi respectively with different inhibition zones starting from 11 to 26 mm. In all cases, the used two doses were (10 mg/ 1 ml in DMSO) and (20 mg/ 1ml DMSO).

Cytotoxic Effects of New Palladium(II) Complexes with Thiazine or Thiazoline Derivative Ligands in Tumor Cell Lines.

The synthesis of analogs of cisplatin, which is a widely used chemotherapeutic agent, using other metal centers could be an alternative for cancer treatment. Pd(II) could be a substitute for Pt(II) due to its coordination chemistry similarity. For that reason, six squared-planar Pd(II) complexes with thiazine and thiazoline ligands and formula [PdCl2(L)] were synthesized and characterized in this work. The potential anticarcinogenic ability of the compounds was studied via cytotoxicity assay in three different human tumor cell lines, i.e., epithelial cervix carcinoma (HeLa), promyelocytic leukemia (HL-60), and histiocytic lymphoma (U-937). Data obtained showed that complexes with methyl substitutions did not modify cell viability, while no-methyl substituted compounds had a moderate cytotoxic effect on all three cell lines. The complexes with phenyl substitutions displayed the lowest IC50 values, which ranged between 46.39 ± 3.99 μM and 62.74 ± 6.45 μM. Moreover, Pd accumulation inside the cell was observed after incubation with any of the four complexes mentioned, and the two complexes with phenyl rings were found to induce an increase in the percentage of apoptotic cells. These results suggested that the presence of bulky substitutions on the ligands such as phenyl groups may influence the cytotoxicity of the chemotherapeutic agents synthesized.

Syntheses and Molecular Docking Analysis of Some New Thiazole and Thiazine Derivatives as Three Armed Molecules with a Triazine Ring as a Core Component: A Search for anti-Obesity Agents

A number of new three-armed heterocycles as thiazoles and thiazines linked to triazine moiety was prepared starting from cyanuaric chloride and thiothemicarbazide which gave the target compound 1. The reaction of the tris-thiosemicarbazide with a variety of hydrazonoyl halides afforded thiazole derivatives. In addition, a thiazole derivative could be prepared from the reaction of the target compound 1 with DMAD. Moreover, thiazine derivatives were synthesized from compound 1 through its interaction with benzylidinemalonitrile. In this work, the molecular docking analysis of thirteen compounds against FTO (Fat mass and Obesity-Associated) protein is carried out to investigate the mode of their molecular interactions. Furthermore, in silico ADMET predictions for the new compounds were calculated with the objective to gain an insight into their pharmacokinetic, safety, and drug-likeness profile. The new compounds could be promising chemical scaffolds for the development of future anti-obesity drug candidates.

Theoretical Study of Reactivity and Stability of a Thiazine Derivative Series by the Density Functional Theory (DFT) Method

The study of the reactivity and stability of the five (05) compounds of Thiazine was carried out using the density functional theory at the level B3LYP/6-31+ G (d, p). The determination of the dual descriptor as well as the analysis of the map of the molecular electrostatic potential (MEP) made it possible to show that the sulfur and nitrogen atoms of the Thiazine cycle are respectively the electrophilic and nucleophilic sites. The study of the chemical reactivity of our compounds was carried out from the analysis of the frontier molecular orbitals (HOMO and LUMO), the energy gap (ΔE), the chemical hardness (η), the electrophilicity index (ω) and electronegativity (χ). Thus, the Thz3 compound is the least reactive, the least electron donor and the most stable of all our compounds.

Synthesis A New Bis Oxazine and Thiazine Derivatives and Study Their Biological Activities

Oxazine and thiazine are heterocyclic organic compounds that have a wide range of pharmacological applications. In this study, some chalcone derivatives (1–5) were synthesized based on the reaction of an equal amount of p-substituted acetophenone and terephthalaldehyde in a basic medium. Oxazine derivatives (6-10) and thiazine derivatives (11–15) are synthesized from the reactions of chalcones (1-5) with urea and thiourea, respectively, in a basic medium. The newly synthesized compounds were identified using various physical techniques like 1H-NMR and FT-IR spectra, in addition to docking analysis for some of these derivatives. Finally, these compounds were tested for their biological activity, IC50, and % of PC3 cell line viability as markers of anticancer activity.

Facile Synthesis, Inhibition of VEGFR-2, Anticancer activity, Molecular Dynamics Simulation and Target Identification of Some New Pyrano thiazine derivatives

Facile Synthesis, Inhibition of VEGFR-2, Anticancer activity, Molecular Dynamics Simulation and Target Identification of Some New Pyrano thiazine derivatives

Synthesis of new thiazine and thiazole derivatives via cyclization reactions; investigating their electronic properties and determination of antioxidant properties

Abstract(4‐[2,4‐dimethoxyphenyl]‐6‐phenyl‐2‐thioxo‐1,2,3,4‐tetrahydropyrimidin‐5‐yl)(phenyl) methanone (1) have been prepared by Biginelli three‐component cyclocondensation reaction of catalyzed with p‐toluene sulfonic acid in ethanol. Pyrimido[2,1‐b]thiazine (2) and thiazolo[3,2‐a]pyrimidine (3) derivatives were obtained by a simple one‐pot condensation reaction of starting compound 1 and 3‐bromopropionic acid, bromoacetic acid and, respectively. By performing the reactions of compound 3 with heteroaromatic and aromatic aldehydes, arylidine‐bicyclic thiazolo pyrimidine compounds (4–9) were synthesized. Theoretical calculations and molecular electrostatic potential maps of all synthesized compounds were performed using the Gaussian software package Density Functional Theory (DFT/6‐31G: B3LYP). In addition, studies were carried out to determine the antioxidant properties of all the compounds obtained by the DPPH method, and compound 1 was found to be the most effective compound. The structures of the newly synthesized compounds were analyzed using spectroscopic methods such as IR, 1H, and 13C.

Convenient Synthesis of 4-pyridinyloxy-Modified imidazo[2,1-b][1,3]thiazines as Potential Anti-inflammatory Agents

Novel imidazo[2,1-b][1,3]thiazine derivatives modified with 4-pyridinyloxyl moiety, as potential anti-inflammatory agents are described. Synthetic approach to the preparation of (6-((pyridin-4-yl)oxy)-6,7-dihydro-5H-imidazo[2,1-b][1,3]thiazines 3a-f and their benzoanelated analogues 3g-j is based on the interaction of substituted 4-fluoropyridines with 3-hydroxy(benzo)imidazo[2,1-b][1,3]thiazines. The nucleophilic substitution reaction of the fluorine atom occurs selectively at position 4 of the pyridine ring. The drug-like properties of the first synthesized (4-pyridinyloxy)imidazo[2,1-b][1,3]thiazines were predicted in silico using SwissADME. Anti-inflammatory activity was studied in vivo using hind paw edema in white rats (carrageenan test). Compounds with satisfactory drug-like and pharmacological properties have been identified as promising for further structure optimization and in-depth research.