Synthesis and characterization of derivatives including thiazolidine-2,4-dione/1-H- imidazole and evaluation of antimicrobial,antioxidant, and cytotoxic properties of new synthetic heterocyclic compounds

Several new derivatives of thiazolidine-2,4-dione and 1-H-imidazole were prepared using imidazole aldehydes 6a–6f in ethanol as a solvent. Products 7a–7f were obtained in reasonable yields and great purity. The antioxidant activity for finish products was evaluated by DPPH radical scavenging activity and showed relatively good activity against ascorbic acid. Compounds 7d, 7e, and 7f had the highest antioxidant activity. Compound 7c showed the lowest amount of IC50 versus ascorbic acid. The antimicrobial activity of these compounds against gram-positive bacteria including Bacillus anthracis (B. anthracis) and Staphylococcus aureus (S. aureus) and gram-negative bacteria including Escherichia coli (E. coli) and Pseudomonas aeruginosa (P. aeruginosa) bacteria was evaluated by the inhibition zone diameter assay method, and the compounds showed moderate to low antibacterial activity. The toxicity properties of all synthesized compounds against cisplatin were investigated. Most of the compounds showed good activity against the positive control group, and the toxicity of compound 7b was higher than that of other compounds.

Graphic abstract

     

The Synthesis and Antimicrobial Screening of Some Novel AZA-Imidoxy Compounds as Potential Chemotherapeutic Agents

Some novel azaimidoxy compounds viz. 2-{[(4-chlorophenyl)diazenyl]oxy}-1H-isoindole-1,3-(2H)-dione (Va), and 1-{[1-naphthyldiazenyl]oxy}pyrrolidine-2,5-dione (IVc), etc. have been synthesized by a simple diazotization reaction followed by a coupling with 2-hydroxy-1H-isoindole-1,3(2H)-dione (III)/1-hydroxypyrrolidine-2,5-dione (II) of corresponding aromatic primary amine derivatives at a suitable pH. A similar reaction with a [1,3]thiazolo[4,5-b]pyridin-2-amine (VIII) lead us to some interesting results variable with a pH. The structure of all synthesized compounds has been established by IR, ¹H NMR, and mass studies. These compounds have been screened for antimicrobial activities in order to evaluate the possibility of the derivatives to be used as potential chemotherapeutic agents.     

Comparative Study of the Structure of Rhodanine, Isorhodanine, Thiazolidine-2,4-dione, and Thiorhodanine

Ab initio (HF and MP2 level) and semiempirical (AM1, PM3, MNDO) calculations on the relative stabilities and structures of the potential tautomeric forms of rhodanine, isorhodanine, thiazolidine-2,4-dione, and thiorhodanine are reported. Ab initio calculations predict that the thiooxo, oxothio, dioxo, and dithio tautomers are the most stable. These results correspond to the known experimental data. Infrared spectra of the investigated compounds were recorded for the region 4000-150 cm^-1, and the characteristic bands were compared with ab initio calculated frequencies at the HF/3-21G^(*)* level.     

Synthesis,structural characterization and antimicrobial activities of cyclochlorotriphosphazene derivatives derived from N-(1-Naphthyl)ethylenediamine

Abstract

The nucleophilic substitution reactions of cylochlorotriphosphazene (N₃P₃Cl₆) with N-(1-Naphthyl)ethylenediamine resulted in the following formation of partially and fully substituted cyclotriphosphazene derivatives: 2,4,4,6,6-pentachloro-2-open-chain-N-(1-Naphthyl) ethylendiamino-cyclotriphosphazatriene (3); 4,4,6,6-tetrachloro-2,2-spiro-N-(1-Naphthyl) ethylendiamino-cyclotriphosphazatriene (4); 2,6,6-trichloro-2-open-chain-4,4-spiro-N-(1-Naphthyl)ethylendiamino-cyclotriphosphazatriene (5); 2,4-dichloro-2,4-ansa-6,6-spiro-N-(1-Naphthyl)ethylendiamino)-cyclotriphosphazatriene (6); and 2,4,6-trichloro-2,4,6-non-gem-open-chain-N-(1-Naphthyl)ethylendiamino)-cyclotriphosphazatriene (7); 2,2,4,4,6,6-tri-spiro-N-(1-Naphthyl)ethylendiamino)-cyclotriphosphazatriene (8); 2,4-dichloro-2,4-cis-open-chain-6,6-spiro-N-(1-Naphthyl)ethylendiamino)-cyclotriphosphazatriene (9); and 2,4,6,6-tetrachloro -2,4-ansa-N-(1-Naphthyl)ethylendiamino)-cyclotriphosphazatriene (10). The reactions produced the 4,4,6,6-tetrachloro-2,2-spiro-N-(1-Naphthyl) ethylendiamino-cyclotriphosphazatriene (4) and 2,4,6,6-tetrachloro-2,4-ansa-N-(1-Naphthyl)ethylendiamino)-cyclotriphosphazatriene (10) derivatives as the major products in this system. The structures of the compounds were characterized by FT-IR, elemental analysis, TLC-MS, FT-IR, ¹H, and ³¹P NMR spectral data. All the derived compounds (3–10) were screened for antimicrobial activity by using the broth-agar microdilution technique for the determination of MIC and MCC values. In this context, the compounds were examined against three different human pathogens; Escherichia coli W3110, Staphylococcus aureus ATCC 25923 and Candida albicans ATCC 10231. Except compounds 6 and 9, the rest of the compounds exhibited significant antimicrobial activity on E. coli (W3110), S. aureus (ATCC 25923) and C. albicans (ATCC 1023). Among the synthesized derivatives, compound 4 is the most active agent against the referenced bacteria.     

Pyrimidines,Part XXXI . Synthesis,reactions and properties of 6-acyl-1,3-dimethylpyrrolo[2,3-d]pyrimidine-2,4-diones

Acylations of 1,3-dimethyl- ( 1 ) and 1,3,7-trimethylpyrrolo[2,3-d]pyrimidine-2,4-dione ( 2 ) with anhydrides in the presence of trifluoroacetic acid proceed well to give in good yields the corresponding 7-acyl derivatives 3–11 . The 6-trichloroacetyl derivatives 5 and 6 are sensitive towards nucleophiles, which displace the trichloromethyl group easily by formation of the corresponding 6-carboxylic acid derivatives 12–23. The newly synthesized compounds have been characterized by elemental analysis, uv and ¹H nmr spectra and pK_a, determinations.     

Synthesis of novel coumarinyl-pyrido[2,3-d]pyrimidine-2,4-diones using task-specific magnetic ionic liquid, [AcMIm]FeCl4 as catalyst

Abstract

An acid-functionalized magnetic ionic liquid, 1-acyl-3-methylimidazolium tetrachloroferrate, [AcMIm]-FeCl₄ has been utilized for the synthesis of a series of novel highly functionalized coumarinyl-pyrido[2,3-d]pyrimidine-2,4-dione derivatives (3a-3l) by the reactions of various 3-chloro-3-(2-oxo-2H-chromen-3-yl)acrylaldehydes (1) with functionalized aryl, 6-aminouracils. The major significant of the present procedure is the use of task-specific acidic ionic liquid which act as catalyst as well as reaction medium and thus avoiding use of organic solvent and/or protic acid catalyst. The other major advantages of the protocol are (i) shorter reaction time (1?h), (ii) easy work up procedure, (iii) excellent yields of products (91-94%), and (iv) recyclability of catalyst. The compounds (3a-3l) were identified using FT-IR, ¹H NMR, and ¹³C NMR and mass spectroscopic studies.     

Cesium carbonate catalyzed efficient synthesis of quinazoline-2,4(1H,3H)-diones using carbon dioxide and 2-aminobenzonitriles

Abstract

An efficient protocol for the synthesis of quinazoline-2,4(1H,3H)-diones derivatives from 2-aminobenzonitriles with carbon dioxide using catalytic amount of cesium carbonate has been developed. 6,7-Dimethoxyquinazoline-2,4(1H,3H)-dione, which is one of the key intermediate for the synthesis of several drugs (Prazosin, Bunazosin and Doxazosin) was synthesized. The effect of different reaction parameters like influences of bases, solvent, temperature, CO₂ pressure and reaction time were investigated for the title reaction.     

Novel imidazole derivatives as antifungal agents: Synthesis,biological evaluation,ADME prediction and molecular docking studies

Abstract

A series of 2-(substituteddithiocarbamoyl)-N-[4-((1H-imidazol-1-yl)methyl)phenyl]acetamide derivatives was designed and synthesized to combat the increasing incidence of drug-resistant fungal infections. All synthesized compounds were characterized by IR, ¹H-NMR, ¹³C-NMR, and HRMS spectra and elemental analyses. Antifungal activity tests were performed against four different fungal strains. Molecular docking studies were performed to investigate the mode of action towards the fungal lanosterol 14α-demethylase, a cytochrome P450-dependent enzyme. ADME studies were carried out and a connection between activities and physicochemical properties of the target compounds was determined. Most of the final compounds exhibited significant activity against Candida albicans and Candida krusei with MIC₅₀ value 12.5?μg/mL. The results of in vitro anti-Candida activity, a docking study and ADME prediction revealed that the newly synthesized compounds have potential anti-Candida activity and evidenced the most active derivative, 5b (2-Pyrrolidinthiocarbonylthio-N-[4-((1H-imidazol-1-yl)methyl)phenyl]acetamide), which can be further optimized as a lead compound.     

Synthesis of physiologically active compounds of the thiosemicarbazone series and derivatives

With a view to discovering new plant growth regulators, a series of thiosemicarbazones and derivatives of thiazolidine-2-4-dione were synthesized. Reaction of epichlorohydrin with derivatives of thiazolidine-2,4-dione without a substituent at positions gives 3-(β-hydroxy-γ-chloropropyl) derivatives of thiazolidine-2, 4-dione-2-hydrazone.     

Synthesis,Structures, and Fungitoxicity of Novel Organophosphorus Compounds

Abstract

A series of biologically active organophosphorus compounds have been synthesized by the reactions of O,O-diethylchlorophosphate with Schiff bases derived from 5-(phenyl/substituted phenyl)-2-hydrazino-1,3,4-oxadiazole and salicylaldehyde/2-hydroxyacetophenone. The compounds have been characterized on the basis of analyses and spectral (IR, ¹H, ¹³C NMR) data. Fungicidal activities of these derivatives against Colletotrichum falcatum, Fusarium oxysporum, and Curvularia pallescence have been evaluated. All compounds showed moderate to significant antifungal activity.     

Urea and thiourea derivatives of 3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1, 2, 4]triazolo[4,3-a]pyrazine: Synthesis,characterization, antimicrobial activity and docking studies

Abstract

An efficient and robust synthetic procedure was developed primarily for the synthesis of a precursor compound; 3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1, 2, 4]triazolo[4,3-a]pyrazine (11), from 2-chloropyrazine (7) through the chemical transformations such as hydrazine substitution, trifluoroacetyl group induction, cyclization and pyrazine ring reduction. A new series of urea derivatives 13a-e and thiourea derivatives 13f-j of compound 11 have been synthesized and the structures of all the compounds were confirmed using spectroscopic analyses such as IR, ¹H NMR, ¹³C NMR, LC-MS and HRMS. The newly synthesized compounds were screened for their in vitro antimicrobial activity against five bacteria and two fungi, in which compounds 13d, 13i and 13j displayed potential activity against bacterial strains and 13a, 13d, 13g and 13j against fungal strains with the MIC values in the range of 6.25–25.0 µg/mL. An overall comparison of the activity results revealed that thiourea derivatives contain better activity than that of urea compounds. Molecular docking studies on poly (ADP-ribose) polymerase 15 (ARTD7, BAL3) demonstrated that all the synthesized compounds possess significant binding energies (-8.1 to -9.8?kcal/mol) with no adverse effect in the active site of protein.     

Synthesis and Characterization of Nitrogen and Sulfur Containing 1,4-Naphthoquinones

Abstract

New N,S-disubstituted naphthoquinones were synthesized by reactions of S- and N-nucleophiles with 2,3-dichloro-1,4-naphthoquinone. 2-(Hexadecylthio)-3-(phenylamino)-naphthalene-1,4-dione 5a was synthesized by reaction of 2-chloro-3-(phenylamino)-naphthalene-1,4-dione 3a with hexadecanethiol 4a. The structures of the new synthesized naphthoquinone derivatives were determined by micro analyses and spectroscopic methods (FT-IR, ¹H NMR, ¹³C NMR, MS, and UV/Vis.). Photo- and electrochemical properties of selected compounds were investigated by using fluorescence spectroscopy and the cyclovoltammetry method.     

Efficient Preparation of 5-Amino-4-cyano-N-(cyclopropylcarbamoyl)-3-aryl-2,3-dihydrothiophene-2-carboxamide Derivatives Without Using Any Other Catalysts

An efficient synthesis of 5-amino-4-cyano-N-(cyclopropylcarbamoyl)-3-aryl-2,3-dihydrothiophene-2-carboxamide derivatives by the reaction of thiazolidine-2,4-dione, aromatic aldehydes, malononitrile, and cyclopropylamine has been reported. This reaction could be carried out smoothly without using any other catalysts in anhydrous ethanol. The advantages of this procure were good yields, short reaction time, and mild reaction conditions. Moreover, the purification process of products was very simple. The products could be gained only as the reactants were cooled under room temperature, and the precipitate could be brought out. These precipitate only need to filter out, without further purification.

Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications® to view the free supplemental file.     

Synthesis and Herbicidal Activity of [(Substituted Phenoxyacetoxy) (Substituted Phenyl)Methyl](Methyl) Phosphinates Containing Fluorine

Abstract

A series of [(substituted phenoxyacetoxy)(substituted phenyl)methyl](methyl)phos- phinates containing fluorine were designed and synthesized. All the synthesized compounds were identified by elemental analysis, IR, ¹H NMR, mass spectrometry. O-methyl [(2-fluorophenoxyacetoxy)(2,4-dichlorophenyl)methyl](methyl)phosphinate was further analyzed by X-ray single-crystal diffraction. Their herbicidal activity against a set of weed species was examined. Some of the compounds showed potential herbicidal activity, which provided some indications for further studies on structure modification.

Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.     

Synthesis of physiologically active compounds of the thiosemicarbazone series and derivatives

With a view to discovering new plant growth regulators, a series of thiosemicarbazones and derivatives of thiazolidine-2-4-dione were synthesized. Reaction of epichlorohydrin with derivatives of thiazolidine-2,4-dione without a substituent at positions gives 3-(-hydroxy--chloropropyl) derivatives of thiazolidine-2, 4-dione-2-hydrazone.     

Synthesis and Structure–Antitumor Activity Relationship of Sulfonyl 5-Fluorouracil Derivatives

Novel sulfonyl 5-fluorouracil derivatives 2 (5-fluoro-1-(arylsulfonyl)pyrimidine-2,4(1H,3H)-diones) have been synthesized via the reaction of 5-fluorouracil with sulfonyl chloride. Their chemical structures were confirmed by means of ¹H NMR, ¹³C NMR, IR, mass spectra, and elemental analyses, and, in the case of 2a, its structure was established by single crystal X-ray diffraction. Some of the compounds were assayed for anticancer (HL-60 and BEL-7402 cells) activities. Structure–activity relationship (SAR) analysis discovered that the anticancer activity was related to the configuration, and that electron-withdrawing groups at 2-position or 4-position on the aryl group of arylsulfonyl derivatives of 5-fluorouracil could enhance the anticancer activity against the BEL-7402 cells.

Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.     

Efficient and facile synthesis of 5-arylindeno[2′,1′:5,6]pyrido[2,3-d] pyrimidine-2,4(3H)-dione and 7-arylbenzo[h]pyrimido[4,5-b]quinoline-8,10(5H,9H)-dione under mild conditions

An efficient and facile method for the synthesis of 5-arylindeno[2′,1′:5,6]pyrido[2,3-d] pyrimidine-2,4(3H)-dione and 7-arylbenzo[h]pyrimido[4,5-b]quinoline-8,10(5H,9H)-dione derivatives from the reactions of 2-arylidene-2,3-dihydroinden-1-one (or 2-arylidene-3,4- dihydronaphthalen-1(2H)-one) and 6-amino-1,3-dimethylpyrimidine-2,4(1H,3H)-dione under mild conditions was described. This is a simple, efficient, and very rapid synthetic method, which is believed to provide a useful process for the synthesis of these fused heterocyclic compounds. The products were confirmed by infrared, ¹H NMR, ¹³C NMR, and high-resolution mass spectrometry.     

Thiazolidinedione Derivatives: In Silico,In Vitro,In Vivo,Antioxidant and Anti-Diabetic Evaluation

This work aimed to synthesize a new antihyperglycemic thiazolidinedione based on the spectral data. The DFT\B3LYP\6-311G** level of theory was used to investigate the frontier molecular orbitals (FMOs), chemical reactivity and map the molecular electrostatic potentials (MEPs) to explain how the synthesized compounds interacted with the receptor. The molecular docking simulations into the active sites of PPAR-γ and α-amylase were performed. The in vitro potency of these compounds via α-amylase and radical scavenging were evaluated. The data revealed that compounds (4–6) have higher potency than the reference drugs. The anti-diabetic and anti-hyperlipidemic activities for thiazolidine-2,4-dione have been investigated in vivo using the alloxan-induced diabetic rat model along with the 30 days of treatment protocol. The investigated compounds didn’t show obvious reduction of blood glucose during pre-treatments compared to diabetic control, while after 30 days of treatments, the blood glucose level was lower than that of the diabetic control. Compounds (4–7) were able to regulate hyperlipidemia levels (cholesterol, triglyceride, high-density lipoproteins and low- and very-low-density lipoproteins) to nearly normal value at the 30th day.     

An efficient synthesis of 3-aryl-2,3-dihydrothiophene-2-carboxamide derivatives by one-pot, four-component reaction

An efficient and convenient method for the preparation of 3-aryl-2,3-dihydr-othiophene-2-carboxamide derivatives in absolute ethyl alcohol by thiazolidine-2,4-dione, aromatic aldehyde, malononitrile and n-butylamine without using any other catalysts was reported. This methodology has the advantages of high yields, simple work-up procedure and mild reaction conditions.     

Bis-Thiourea Bearing Aryl and Amino Acids Side Chains and Their Antibacterial Activities

Abstract

A series of symmetrical 1,3-bis thiourea 1a–e and 1,4-bis thiourea derivatives 2a–e have been successfully synthesized from the reactions of amines with 3-acetylbenzoyl isothiocyanate and 4-acetylbenzoyl isothiocyanate, respectively. All the synthesized compounds were characterized by FT-IR spectroscopy and ¹H and ¹³C NMR spectroscopy. The compounds were screened for their antibacterial activity by turbidimetric method using gram-negative bacteria (E. coli ATCC 8739) using turbidimetric method. The newly synthesized bis-thiourea derivatives bearing aryl side chains showed good antibacterial activity against E. coli. The effect of the molecular structure of the synthesized compounds on the antibacterial activity is discussed.