Ingrida Tumosienė

The synthesis of azole derivatives from 3-[(4-methylphenyl)amino]propanehydrazide and its N′-phenylcarbamoyl derivatives, and their antibacterial activity

Abstract5-[2-[(4-Methylphenyl)amino]ethyl]-1,3,4-oxadiazol-2(3H)-thione, 5-[2-[(4-methylphenyl)amino]ethyl]-1,3,4-oxadiazol-2(3H)-one, N-(2,5-dimethyl-1H-pyrrol-1-yl)-3-[(4-methylphenyl)amino]propanamide, and a series of N-[(phenylcarbamoyl)amino]-3-[(4-methylphenyl)amino]propanamides and 3-[(4-methylphenyl)(phenylcarbamoyl)amino]-N-[(phenylcarbamoyl)amino]propanamides, and their thio analogues were synthesized from 3-[(4-methylphenyl)amino]propanehydrazide. 1,3,4-Oxadiazole-2(3H)-thione was converted to 4-amino-2,4-dihydro-5-[2-[(4-methylphenyl)amino]ethyl]-3H-1,2,4-triazole-3-thione, whereas cyclization of N′-phenylcarbamoyl derivatives provided thiazole, oxadiazoles, and thiadiazole, as well as triazole derivatives. Two of the synthesized compounds exhibited good antibacterial activity against Rhizobium radiobacter.Graphical abstract

4-Amino-substituted Benzenesulfonamides as Inhibitors of Human Carbonic Anhydrases

A series of N-aryl-β-alanine derivatives and diazobenzenesulfonamides containing aliphatic rings were designed, synthesized, and their binding to carbonic anhydrases (CA) I, II, VI, VII, XII, and XIII was studied by the fluorescent thermal shift assay and isothermal titration calorimetry. The results showed that 4-substituted diazobenzenesulfonamides were more potent CA binders than N-aryl-β-alanine derivatives. Most of the N-aryl-β-alanine derivatives showed better affinity for CA II while diazobenzenesulfonamides possessed nanomolar affinities towards CA I isozyme. X-ray crystallographic structures showed the modes of binding of both compound groups.

The synthesis of S-substituted derivatives of 3-[2-[(4-methylphenyl)amino]ethyl]-4-phenyl-4,5-dihydro-1H-1,2,4-triazole-5-thiones and their antioxidative activity

A series of novel S-substituted derivatives of 3-[2-[(4-methylphenyl)amino]ethyl]-4-phenyl-4,5-dihydro-1H-1,2,4-triazole-5-thiones was synthesized by the reaction of 1,2,4-triazole-5-thiones with alkyl, benzyl, and phenacyl halides as well as halogen-containing esters or amides. The reactions were carried out in DMF in the presence of KOH, K2CO3, or triethylamine, or in dioxane in the presence of NaH. The synthesized compounds were screened for their free radical scavenging activity. N-[2-[5-(Butylsulfanyl)-4-phenyl-4H-1,2,4-triazol-3-yl]ethyl]-4-methylaniline showed excellent antioxidant activity, 2.5 times higher than that of the antibiotic control (cefazolin).Graphical abstract

N′-(1,3-Dithiolan-2-ylidene)-3-(phenylamino)propanehydrazide

A synthesis of N′-(1,3-dithiolan-2-ylidene)-3-(phenylamino)propanehydrazide from 3-(phenylamino)propanehydrazide, carbon disulfide and 1,2-dibromoethane is reported. The title compound was characterized by 1H NMR, 13C NMR, ESI/MS, and elemental analysis.

Synthesis of novel 1,2- and 2-substituted benzimidazoles with high antibacterial and antioxidant activity

Benzimidazole derivatives are potential candidates for drug development. They are efficiently synthesized and possess various biological properties including antibacterial activity. A series of functionalized benzimidazole derivatives bearing N-(4-chloro- or fluorophenyl)pyrrolidin-2-one or N-(4-chloro- or fluorophenyl)aminobutanoic acid moiety were synthesized. Compounds possessing a very high antibacterial activity, comparable to that of a commercial antibacterial agent oxytetracycline, against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Bacillus cereus were identified. Some of the synthesized compounds exhibited significant antioxidant activity.Graphical abstract

Benzenesulfonamides bearing pyrrolidinone moiety as inhibitors of carbonic anhydrase IX: synthesis and binding studies

A series of novel compounds bearing substituted pyrrolidinone moieties at the para-position of benzenesulfonamide was synthesized as inhibitors of carbonic anhydrase (CA) isoform IX, known to be overexpressed in numerous human cancers. The inhibitors were tested towards all twelve catalytically active human CA isozymes to determine the affinity and selectivity towards CA IX over other isoforms. Compound affinity was determined by the fluorescence-based thermal shift assay and verified by isothermal titration calorimetry. Several compounds exhibited nanomolar binding affinity against CA IX while significantly weaker binding to the cytosolic off-target CA I was observed. The most effective CA IX binders reached the Kd of about 50 nM. This series of compounds can be used for further development of inhibitors with significant binding affinity and selectivity towards anticancer CA IX isozyme.