Kristina Kantminienė

Synthesis and Antimicrobial Activity of N-Substituted-β-amino Acid Derivatives Containing 2-Hydroxyphenyl, Benzo[b]phenoxazine and Quinoxaline Moieties

3-[(2-Hydroxyphenyl)amino]butanoic and 3-[(2-hydroxy-5-methyl(chloro)phenyl)amino]butanoic acids were converted to a series of derivatives containing hydrazide, pyrrole and chloroquinoxaline moieties. The corresponding benzo[b]phenoxazine derivatives were synthesized by the reaction of the obtained compounds with 2,3-dichloro-1,4-naphthoquinone. Five of the synthesized compounds exhibited good antimicrobial activity against Staphylococcus aureus and Mycobacterium luteum, whereas three compounds showed significant antifungal activity against Candida tenuis and Aspergillus niger.

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.

N-Sulfamoylphenyl- and N-sulfamoylphenyl-N-thiazolyl-β-alanines and their derivatives as inhibitors of human carbonic anhydrases

A series of N-substituted and N,N-disubstituted β-amino acids and their derivatives bearing benzenesulfonamide moiety were designed and synthesized in search of compounds that would be high-affinity and selective inhibitors of human carbonic anhydrases (CA). There are 12 catalytically active human CA isoforms, the cytosolic CA I, CA II, CA III, CA VII, and CA XIII, secreted CA VI, the mitochondrial CA VA and CA VB, membrane-associated CA IV, and transmembrane CA IX, CA XII, and CA XIV. The di-bromo meta-substituted compounds exhibited low nanomolar dissociation constants and over 10-fold selectivity for mitochondrial isozyme CA VB, implicated in diseases of the central nervous system and obesity. These compounds can be used for further development as inhibitors of significant binding affinity and selectivity towards CA VB isozyme.

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.

Unexpected transformation of ethyl 1-(4-chlorophenyl)-2-methyl-4-oxo-1,4,5,6-tetrahydropyridine-3-carboxylate and antibacterial activity of the products

The cyclization reaction of N-(4-chlorophenyl)-β-alanine, in the presence of piperidine as a catalyst, provided ethyl 1-(4-chlorophenyl)-2-methyl-4-oxo-1,4,5,6-tetrahydropyridine-3-carboxylate, which reactions with different hydrazines were carried out resulting in formation of a variety of tetrahydropyridine, dihydropyrazolone, and oxazole derivatives in good yields. 5-[2-[(4-Chlorophenyl)amino]ethyl]-4-(1-hydrazinylethylidene)-2,4-dihydro-3H-pyrazol-3-one was converted into a series of hydrazones, which provided tetrahydro-3H-pyrazolo[4,3-c]pyridin-3-one under treatment with acids. The structures of all synthesized compounds were confirmed by IR, 1H NMR, and 13C NMR spectroscopy. The structures of three compounds were unambiguously assigned by means of X-ray analysis data. Some of the synthesized compounds exhibited weak antibacterial activity.Graphical Abstract

Alkylation of 1-(3,4-Disubstituted Phenyl)-2-thioxo-1,2,5,6-tetrahydropyrimidin-4(3H)-ones

The results of a comprehensive investigation of the alkylation of the title compounds with MeI in butanone in the presence of K2CO3 are presented.

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.