A facile synthesis and antimicrobial activity evaluation of sydnonyl-substituted thiazolidine derivatives.

Some new sydnonyl-substituted thiazolidine derivatives were synthesized in high yields by the modified Knoevenagel condensation of 3-aryl-4-formylsydnones with thiazolidine-2,4-dione and 2-thioxo-thiazolidine-4-one, respectively. All the synthesized thiazolidine derivatives were screened by paper-disc method to identify their antimicrobial activities against three bacteria viz. Staphylococcus aureus, Proteus vulgaris and Escherichia coli, and two fungal cultures viz. Aspergillus niger and Penicillium citrinum. The reference drugs were Norfloxacin and Griseofulvin, respectively. The screening data indicated that the tested sydnonyl-substituted thiazolidine derivatives exhibited no obvious antibacterial activity compared with the standard drug Norfloxacin. However, thiazolidine derivatives displayed significant antifungal activities against Penicillium citrinum and Aspergillus niger. Notably, all of the tested compounds showed growth inhibitory activity 1.5-4.4 times higher than that of the standard drug Griseofulvin against the two fungi.

Syntheses of nickel (II) complexes from novel semicarbazone ligands with chloroformylarylhydrazine, benzimidazole and salicylaldehyde moieties.

This study addressed the design and syntheses of diverse ligands, which were then successfully treated with Ni (II) ion to afford a series of nickel complexes. α-Chloroformylarylhydrazine hydrochlorides contain two different functional groups. One is a strong nucleophile, and the other is a good electrophile. Therefore, it can be designed to react with several reagents to obtain diverse derivatives which can be used as ligands for metal complexes. Furthermore, benzimidazole and salicylaldehyde can provide electron donor sites, N and O electron donors, separately. Hence, the starting materials α-chloroformylarylhydrazine hydrochlorides were first treated with 2-(aminomethyl)-benzimidazole (7) to give the corresponding semicarbazides. Then, the semicarbazides 8 reacted with various substituted salicylaldehydes to afford the desired substituted-salicylaldehyde 2-aryl-4-substituted semicarbazones, which could coordinate with nickel (II) ion to give the corresponding nickel complexes.

Novel synthesis of palladium (II) complexes derived from 3-arylsydnone-4-carbaldehyde N(4)-phenylthiosemicarbazones and biological activity.

OBJECTIVES: The aim of this research is to investigate whether the oxygen atom O(6) in the sydnone ring of 3-arylsydnone-4-carbaldehyde N(4)-phenylthiosemicarbazones (HArSYTSCs, 3a-d) is a good electron donor atom upon metal complexation. Furthermore, ligands 3a-d and the corresponding palladium complexes (Pd(ArSYTSC)Cl, 4a-d) would be expected to find their potent biological activities. METHODS: The desired palladium complexes 4a-d were first synthesized from thiosemicarbazones 3a-d. Then, the antiproliferative activity of ligands 3a-d and complexes 4a-d were tested against human hepatocellular carcinoma and human cervical epithelioid carcinoma (HeLa) cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl trazolium bromide (MTT) assay. KEY FINDINGS: According to X-ray analyses, ligands 3a-d are bonded to the Pd (II) center in an O, N, S-tridentate coordination mode through sydnone carbonyl oxygen O(6), azomethine nitrogen and the thiolate sulfur atom. The carbonyl oxygen of the sydnone ring is found to be a good electron donor site upon metal complexation. Moreover, MTT assay results reveal that the palladium complexes 4a-d have greater antiproliferative activity than 5-fluorouracil. In particular, the complexes exhibit obvious better activity than the corresponding ligands 3a-d against HeLa cell. CONCLUSIONS: The results indicate that the synthesized novel palladium complexes have greater antiproliferative activity than both 5-fluorouracil and the corresponding ligands against HeLa cell. Accordingly, the study of sydnonyl complexes bearing anticancer activities may support the development of coordination chemistry.

Syntheses of aromatic substituted hydrazino-thiazole derivatives to clarify structural characterization and antioxidant activity between 3-arylsydnonyl and aryl substituted hydrazino-thiazoles.

This work clarifies the structural characterization and antioxidant activity between aromatic and 3-arylsydnonyl substituted hydrazino-thiazoles by further synthesizing a series of aromatic ring-substituted hydrazino-thiazole derivatives 8a-h and 9a-h. Hydrazino-thiazole derivatives 8a-h and 9a-h were obtained by reacting aromatic or heterocyclic aromatic aldehyde thiosemicarbazones 7a-h with cyclization reagents ethyl 2-chloroacetoacetate (2a) and 2-bromoacetophenone (2b), respectively. The ORTEP drawings of compounds 8g, 8h and 9f provide strong evidence of the structure of aromatic thiazole derivatives 8a-h and 9a-h. Undoubtedly, the structure of compounds 3e-h and 4e-h synthesized by the reaction of 3-aryl-4-formylsydnone thiosemicarbazones 1e-h with cyclization reagents 2a and 2b in the previous work should have the thiazole moiety, and not the thiazoline moiety. Both the new thiazole derivatives 8a-h and 9a-h and the 3-arylsydnonyl-substituted derivatives 3e-h and 4e-h were investigated to determine their antioxidant activity by two tests that have been highly documented-the direct scavenging effect on a stable free 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and the inhibition of the 2,2-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical. Results of this study demonstrate that not only the thiazole ring and the aryl ring has the contribution to the antioxidant activities, the sydnone ring of 3-arylsydnonyl moiety also has its considerable contribution.

Syntheses and evaluation of antioxidant activity of sydnonyl substituted thiazolidinone and thiazoline derivatives.

3-Aryl-4-formylsydnone 4'-phenylthiosemicarbazones (3a-d) and 3-aryl-4-formylsydnone thiosemicarbazones (3e-h), which are precursors of 3-aryl-4-heterocyclic sydnones, are prepared by the condensation of 3-aryl-4-formylsydnones (1a-d) with 4'-phenylthiosemicarbazide (2a) and thiosemicarbazide (2b), respectively. The thiosemicarbazones 3 reacted with cyclic reagents such as ethyl chloroacetate (4a), ethyl 2-chloroacetoacetate (4b) and 2-bromoacetophenone (4c) to produce heterocyclic substituted sydnone derivatives 5-7 that possess 4-oxo-thiazolidine and thiazoline groups. The antioxidant activity of synthesized compounds 5a-7h was evaluated. Among these compounds, 4-methyl-2-[(3-arylsydnon-4-yl-methylene)hydrazono]-2,3-dihydro-thiazole-5-carboxylic acid ethyl ester (6e-h) and 4-phenyl-2-[(3-arylsydnon-4-yl-methylene)hydrazono]-2,3-dihydro-thiazoles (7e-h) exhibit the potent DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging activity, comparable to that of vitamin E.