An efficient synthesis of new thiazolidin-4-one fused s-triazines as potential antimicrobial and anticancer agents

As a part of our endeavor toward the synthesis of new heterocyclic bioactive agents, two series of thiazolidin-4-one fused s-triazines were synthesized by applying an efficient palladium catalyzed C–C Suzuki coupling using catalyst system Pd(OAC)₂, Xphos and K₃PO₄ as a base in toluene solvent. Moreover, the synthesized analogs were further screened for their in vitro antimicrobial as well as anticancer efficacy against prostate cancer PC3 cells. Some compounds displayed remarkable antimicrobial activity and noticeable anticancer activity. It was observed that, both benzonitrile and nicotinonitrile are essential to increase the different pharmacological activities. The newly synthesized compounds were characterized by IR, 1H NMR, 13C NMR and MS analysis.     

Synthesis and antioxidant activity of some thiazolidin-4-one derivatives

Abstract  4-Fluorobenzaldehyde was used for the preparation of 2-(4-fluorophenyl)thiazolidin-4-one derivatives which were allowed to react with chloroacetonitrile and acrylonitrile to produce 3-(2-(4-fluorophenyl)-4-oxothiazolidine3-yl)acetonitrile and 3-(2-(4-fluorophenyl)-4-oxothiazoledine-3-yl)propanenitrile. Biological evaluation of some of the compounds showed that many had promising antioxidant activity. Graphical Abstract        

One-pot synthesis of 1, 3-thiazolidin-4-one using Bi(SCH2COOH)3 as catalyst

A catalytic multi-component reaction involving aromatic amine,aromatic aldehydes,mercapto acid as substrates and Bi（SCH₂COOH）₃ as catalyst under solvent free conditions,afforded thiazolidin-4-one in good yields.The efficiency of the catalyst was proved with a variety of substrates,ranging from electrondeficient to electron-rich aldehydes.     

Design,synthesis and antibacterial activity of novel pleuromutilin derivatives with 4H-pyran-4-one and pyridin-4-one substitution in the C-14 side chain

A series of novel pleuromutilin derivatives with 4H-pyran-4-one and pyridin-4-one substitution in the C-14 side chain have been designed and synthesized. In vitro antibacterial activity evaluation showed that most of the derivatives exhibited potent antibacterial activity against drug resistant Gram-positive strains. Compounds 12a, 12d, and 28 are the most active derivatives in this series, displaying activity comparable to that of retapamulin and BC-3781. As the metabolic stability of this series is not satisfactory, further modifications are going on to improve their pharmacokinetic profile.     

Efficient synthesis of 5-substituted thiazolidin-2-ones from xanthates and tert-butyl N-allylcarbamates

A series of 5-substituted thiazolidin-2-ones with various functional groups was synthesized efficiently via a radical addition of xanthates and tert-butyl N-allylcarbamates and subsequent 88% HCO₂H-catalyzed cyclization. The mechanism of the acid-catalyzed cyclization was proposed as well.     

A new application of diphenylphosphorylazide (DPPA) reagent: convenient transformations of quinolin-4-one, pyridin-4-one and quinazolin-4-one derivatives into the 4-azido and 4-amino counterparts

Herein, we describe a transformation of the oxo-function of a series of quinolin/pyridin/quinazolin-4-ones into 4-azido and thence into 4-amino derivatives in moderate yields by a very short and convenient new procedure using DPPA (diphenylphosphoryl azide) as reagent. A mechanism for this interesting new application of DPPA is suggested based on the identification of some of the intermediates.     

Synthesis of Some Novel 5-(Arylidene)-2-imino-3(pyridin-2-yl)thiazolidin-4-one Derivatives

Treatment of 2-aminopyridine ( 1 ) with chloroacetyl chloride in dry benzene gave 2-chloro-N-(pyridin-2-yl)acetamide ( 3 ), which on further reaction with potassium thiocyanate gave 2-imino-3-(pyridin-2-yl)thiazolidin-4-one ( 4 ) as an intermediate compound for the synthesis of pyridin-2-yl substituted 2-imino-thiazolidine-4-one derivatives. Cyclocondensation reaction of ( 4 ) with a series of aromatic aldehydes gave 5-arylidene derivatives of pyridin-2-yl substituted 2-imino-thiazolidine-4-ones 5a–j . ¹ H and ¹³C NMR spectroscopy, as well as elemental analyses, were used for the identification of these new compounds.     

Chelate synthesis of 2,2′-bipyridin-4-one

A method for the synthesis of 2,2′-bipyridin-4-one from 4-amino-4-(2-pyridyl)-but-3-en-2-onevia its diphenylboron, chelates was proposed. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2071–2073, November, 1997.     

Synthesis of 1,2,3-benzotriazin-4-one derivatives containing spirocyclic indoline-2-one moieties and their nematicidal evaluation

To discover new chemotypes of nematicides with proper toxicological profiles, a series of novel 1,2,3- benzotriazin-4-one derivatives were synthesized and further bioevaluated. The bioassay results showed that most of the synthesized compounds were endowed with moderate to good control efficacy against Meloidogyne incognita at 10.0 mg/L in vivo. Among them, compounds 6k and 6p displayed 100% inhibitory activities at this concentration, which implied that they could be used as lead compounds for promising nematicides.     

An improved procedure for the synthesis of 4-methylimidazol-2-one

A novel one-pot synthetic method of 4-methylimidazol-2-one is described. The target compound is conveniently synthesized from sodium diformylamide, a modified Gabriel reagent prepared, through condensation, hydrolyzation and cyclization reactions without separating intermediates, its total yield is 75.8%.     

Design and characterisation of novel hexadentate 3-hydroxypyridin-4-one ligands

Two novel hexadentate 3-hydroxypyridin-4-one ligands have been designed and synthesised. The physico-chemical properties of one of the hexadentate ligands have been determined and the results indicate that the hexadentate ligand possesses high affinity for iron(III).     

Vibrational assignment, structure and intramolecular hydrogen bond of 4-methylamino-3-penten-2-one

The molecular structure, intramolecular hydrogen and vibrational frequencies of 4-methylamino-3-penten-2-one were investigated by a series of density functional theoretical (DFT) calculations and ab initio calculation at the post-Hartree-Fock (MP2) level. Fourier transform infrared and Fourier transform Raman spectra of this compound and its deuterated analogue were clearly assigned. The calculated geometrical parameters show a strong intramolecular hydrogen bond with a N...O distance of 2.622-2.670 A. This bond length is about 0.02 A shorter than that in its parent, 4-amino-3- penten-2-one which is in agreement with spectroscopic results. Furthermore, the conformations of methyl groups with respect to the plane of the molecule and with respect to each other were investigated.     

An Efficient and Convenient Protocol for the Synthesis of Thiazolidin-4-Ones

Abstract

Without a catalyst and under solvent-free conditions, 2,3-disubstituted-1,3-thiazolidin-4-one 5a–j derivatives were synthesized efficiently via the three-component reaction of aryl hydrazide, aromatic aldehyde, and mercaptoacetic acid. All the newly synthesized compounds were confirmed by IR, ¹H NMR, and ¹³C NMR spectroscopy and elemental analysis.

GRAPHICAL ABSTRACT      

Design,Synthesis and Antitumor Activity of Novel Indolin-2-one Derivatives Containing 4-Thiazolidinone Moiety

A series of novel indolin-2-one derivatives containing 4-thiazolidinone moiety(7a―7r) were synthesized and evaluated for their in vitro antitumour activities against MDA-MB-231(human breast cancer), H460(human lung cancer) and HT-29(human colon cancer) cell lines by standard 3-(4,5-dimethylthiazae-2-yl)-2,5-diphenyltetrazo- lium bromide(MTT) assay. Representative compounds(7d, 7k, 7m, 7p) with higher cytotoxicity were further examined against one normal cell line(WI-38, human fetal lung fibroblasts). The preliminary investigation shows that most of the compounds display moderate to excellent potency and high selectivity against different human cancer cell lines. In particular, the most potent compound 7m shows promising cytotoxicity against MDA-MB-231, H460 and HT-29 cell lines with IC₅₀ values of 0.78, 0.056 and 0.018 μmol/L, respectively. The potency is much higher than that of Sunitinib(IC₅₀=3.46 μmol/L against MDA-MB-231, IC₅₀=2.59 μmol/L against H460, IC₅₀=1.50 μmol/L against HT-29) by 4.4, 46.3 and 83.3 fold.     

Synthesis, antibacterial and antifungal activity of some derivatives of 2-phenyl-chromen-4-one

Some derivatives of 2-phenyl-chromen-4-one (flavone ring) have been synthesized and tested for antibacterial and antifungal activities along with their chalcone precursors against four human pathogenic bacteria and five plant mould fungi. The structures of the synthesized compounds were elucidated by UV, IR and¹H NMR spectroscopic techniques, and elemental analysis. The antibacterial and antifungal screens of the synthesized compounds were performed in vitro by the filter paper disc diffusion method and the poisoned food technique.     

Design,synthesis and in vitro biological evaluation of novel 4-methoxy-5-hydroxycanthin-6-one derivatives as potential anti-tumor agents

Abstract

Canthin-6-one analogue, 4-methoxy-5-hydroxycanthin-6-one (CAN1) was isolated from Picrasma quassioides (D.Don) Benn., and a series of derivatives containing the CAN1 framework were designed, synthesized, and evaluated for anti-proliferative activity against two human cancer cell lines, HepG2 and HCT116. Among these compounds, the most representative compound d exhibited better anti-proliferative activities in vitro compared with the positive control Fluorouracil (5-FU), with IC₅₀ values of 5.05?μM (HepG2) and 6.65?μM (HCT116), respectively. Compound d triggered more significant HepG2 cell apoptosis than 5-FU did in a dose-dependent manner. Furthermore, western blot assay indicated that d could enhance the expression of p65 while promoting pro-apoptotic proteins and suppressing the anti-apoptotic proteins in a dose-dependent manner. All these results demonstrated that d might be a potential agent for cancer therapy deserving further exploring.     

Synthesis,characterization and cytotoxic activity of diorganotin (IV) complexes with 4H-pyrido[1,2-a]pyrimidin-4-one derivatives

The coordination behaviour of the diorganotin (IV) compounds R₂SnCl₂ (where R = Me, Ph) with 4H-pyrido [1,2-a] pyrimidin-4-one derivatives (L) has been described. The complexes R₂SnCl₂ · L obtained have been characterized physicochemically and spectroscopically. The pyrimidin-4-one ligands were found to coordinate with R₂SnCl₂ species in a monodentate fashion, mainly via the oxygen atom of the 4-one group or possibly via the nitrogen atom of the (SINGLE BOND)C(DOUBLE BOND)N linkage (the less sterically hindered nitrogen of the pyrimidine derivative) to give pentacoordinate tin complexes. Of the complexes selected to be screened against five tumour cell lines, some exhibited significant in vitro activity.     

Design,synthesis and antifungal activity of novel selenochroman-4-one derivatives

A series of novel selenochroman-4-one derivatives bearing semicarbazone or nitrogen heterocycle was designed, synthesized, tested antifungal activity and characterized via ¹H-NMR, ¹³C-NMR, and HRMS. The design of the compounds is based on the principle of molecule hybrid and bioisosterism. We aimed at attaching semicarbazones or nitrogen heterocycle to the selenochroman-4-one for enhancing antifungal activity. The antifungal activity of target compounds was evaluated using the microdilution broth method in vitro test. Bioassay results indicated that some of the derivatives displayed good fungistatic activity on Candida zeylanoides, Candida albicans, Cryptococcus neoformans, resistant to fluconazole strain 103 (Candida albicans), resistant to fluconazole strain 100 (Candida albicans) and strain SC5314 (Candida albicans). All the compounds exhibit antifungal activities against the tested funguses in different levels, among them, 7 compounds of antifungal activity against several funguses is better than that of the control drug fluconazole. Based on the results, preliminary structure activity relationships (SARs) were summarized to serve as a foundation for further investigation.     

Design and Synthesis of Tri-substituted Chiral Pyrrolidin-2-one Derivatives as CCR4 Antagonists

A series of tri-substituted chiral pyrrolidin-2-one derivatives have been designed and synthesized as CC chemokine receptor 4 （CCR4） antagonists. The structure of CCR4 was built by homology modeling. Asymmetric synthesis was applied to synthesize the R,R configuration chiral pyrrolidin-2-one scaffold. The stereoisomeric con- figurations of the compounds were identified by 2D I H-~H COSY spectroscopy and 1D NOESY spectroscopy. This method was more economical and convenient than traditional X-ray single crystal diffraction. In addition, the inter- actions between these compounds and the N-terminal extracellular tail of CCR4 were studied using capillary zone electrophoresis. The CCR4 chemotaxis inhibition effect was tested in CCR4-transfected HEK293 cells. Several compounds showed potent activities as CCR4 antagonists. Among these compounds, lc is the most active one. Its apparent binding constant of CZE experiment result is （1.569±0.11）× 10s L·mol ^-1, and its percentage inhibition of the HEK293/CCR4 cells migration with the concentration of I gmol·L ^-1 in DMSO is 59%. And compound If has slightly higher affinity to N-terminal of CCR4 according to its apparent binding constant than lb because of the in- troduced ester linkage. Further studies on the mechanism of these compounds are in progress.