Pub Date : 2021-06-30DOI: 10.15407/bioorganica2021.01.010
Y. Kornii, O. Shablykin, O. Shablykina, V. Brovarets
A number of sulfamides were obtained by reaction of (5-(dichloromethylene)-2-oxoimidazolidin-4-ylidene)sulfamoyl chloride with anilines, benzylamines, Boc-protected piperazine, methylalylamine, and amino acids methyl esters with primary and secondary amino group. The antiviral and anticancer activity of new derivatives was evaluated. The most effective compounds against Human cytomegalovirus were sulfamides based on anisidine (1b), N-Boc-piperazine (1h), and the derivatives 1n,o with fragments of nipecotic and azetidine-3-carboxylic acids, respectively. Anticancer activity was most significant for sulfamides based on p-methoxybenzylamine (compound 1d), benzylmethylamine (compound 1f), and allylmethylamine (compound 1g).
{"title":"New 4-iminohydantoin sulfamide derivatives with antiviral and anticancer activity","authors":"Y. Kornii, O. Shablykin, O. Shablykina, V. Brovarets","doi":"10.15407/bioorganica2021.01.010","DOIUrl":"https://doi.org/10.15407/bioorganica2021.01.010","url":null,"abstract":"A number of sulfamides were obtained by reaction of (5-(dichloromethylene)-2-oxoimidazolidin-4-ylidene)sulfamoyl chloride with anilines, benzylamines, Boc-protected piperazine, methylalylamine, and amino acids methyl esters with primary and secondary amino group. The antiviral and anticancer activity of new derivatives was evaluated. The most effective compounds against Human cytomegalovirus were sulfamides based on anisidine (1b), N-Boc-piperazine (1h), and the derivatives 1n,o with fragments of nipecotic and azetidine-3-carboxylic acids, respectively. Anticancer activity was most significant for sulfamides based on p-methoxybenzylamine (compound 1d), benzylmethylamine (compound 1f), and allylmethylamine (compound 1g).","PeriodicalId":23438,"journal":{"name":"Ukr. Bioorg. Acta 2021, Vol. 16, N1","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88086562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-06-30DOI: 10.15407/10.15407/bioorganica2021.01.034
Yevheniia Velihina, N. Obernikhina, S. Pilyo, M. Kachaeva, O. Kachkovsky
The binding affinity of model peptide moieties (Pept) and heterocyclic bases involving 1,3-oxazoles that are condensed with pyridine and pyrimidine as pharmacophores (Pharm) was investigated in silico and analyzed within the «fragment-to-fragment» approach. The anellation of the heterocyclic rings increasing their acceptor properties is accompanied by gaining stability of the [Pharm-Pept] complexes formed by the π,π-stacking interaction. It was found that elongation of the polypeptide chain led to a twofold increase of the stabilization energy of the [Pharm-Pept] complexes. The stability of the hydrogen bonding ([HB]) [Pharm-BioM] complexes formed by means of the interaction between the dicoordinated nitrogen atom of the heterocycle and the functional groups of peptide amino acids (-OH, -NH2, -SH) was evaluated. It was demonstrated that [HB]-complexes that were formed by hydrogen bonds formation with amino acid that contained OH groups had the largest stabilization effect. The anellation with pyridine and pyrimidine rings led to stability increase of the complexes formed by the hydrogen bonding mechanism. The binding energy of [HB]-complexes for compounds 2b and 3 with a «free» peptide bond of the extended part of the protein is lower compared to amino acids with OH-functional groups. On the contrary, the binding energy of compound 4 with peptides was 2 kcal/mol higher. Compound 4 demonstrated the most pronounced biological activity in vitro studies.
{"title":"In silico study the interaction of heterocyclic bases with peptide moieties of proteins in the \"fragment-to-fragment\" approach","authors":"Yevheniia Velihina, N. Obernikhina, S. Pilyo, M. Kachaeva, O. Kachkovsky","doi":"10.15407/10.15407/bioorganica2021.01.034","DOIUrl":"https://doi.org/10.15407/10.15407/bioorganica2021.01.034","url":null,"abstract":"The binding affinity of model peptide moieties (Pept) and heterocyclic bases involving 1,3-oxazoles that are condensed with pyridine and pyrimidine as pharmacophores (Pharm) was investigated in silico and analyzed within the «fragment-to-fragment» approach. The anellation of the heterocyclic rings increasing their acceptor properties is accompanied by gaining stability of the [Pharm-Pept] complexes formed by the π,π-stacking interaction. It was found that elongation of the polypeptide chain led to a twofold increase of the stabilization energy of the [Pharm-Pept] complexes. The stability of the hydrogen bonding ([HB]) [Pharm-BioM] complexes formed by means of the interaction between the dicoordinated nitrogen atom of the heterocycle and the functional groups of peptide amino acids (-OH, -NH2, -SH) was evaluated. It was demonstrated that [HB]-complexes that were formed by hydrogen bonds formation with amino acid that contained OH groups had the largest stabilization effect. The anellation with pyridine and pyrimidine rings led to stability increase of the complexes formed by the hydrogen bonding mechanism. The binding energy of [HB]-complexes for compounds 2b and 3 with a «free» peptide bond of the extended part of the protein is lower compared to amino acids with OH-functional groups. On the contrary, the binding energy of compound 4 with peptides was 2 kcal/mol higher. Compound 4 demonstrated the most pronounced biological activity in vitro studies.","PeriodicalId":23438,"journal":{"name":"Ukr. Bioorg. Acta 2021, Vol. 16, N1","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82088555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-06-30DOI: 10.15407/bioorganica2021.01.003
Yupiao Zou, Zizhen Yin, Haibo Mei, H. Konno, H. Moriwaki, V. Soloshonok, Jianlin Han
Using platform of a new type of chiral Ni(II) complex of glycine Schiff base we designed addition-cyclization reaction cascade to explore aspects of kinetic/thermodynamic formation of the corresponding (S)(2S,3S)/(S)(2S,3R) diastereomers. It was found that the final lactone products reflect the thermodynamic stereocontrol due to much greater rates of the reversible aldol addition vs. subsequent cyclization step. The observed 4/1 (S)(2S,3S)/(S)(2S,3R) diastereoselectivity in the reactions of new type of (S)-Ni(II) complexes constitute an improvement over the previously reported 1.7/1 ratio.
{"title":"Aldol Addition-Cyclization Reaction Cascade on a Platform of Chiral Ni(II) Complex of Glycine Schiff Base","authors":"Yupiao Zou, Zizhen Yin, Haibo Mei, H. Konno, H. Moriwaki, V. Soloshonok, Jianlin Han","doi":"10.15407/bioorganica2021.01.003","DOIUrl":"https://doi.org/10.15407/bioorganica2021.01.003","url":null,"abstract":"Using platform of a new type of chiral Ni(II) complex of glycine Schiff base we designed addition-cyclization reaction cascade to explore aspects of kinetic/thermodynamic formation of the corresponding (S)(2S,3S)/(S)(2S,3R) diastereomers. It was found that the final lactone products reflect the thermodynamic stereocontrol due to much greater rates of the reversible aldol addition vs. subsequent cyclization step. The observed 4/1 (S)(2S,3S)/(S)(2S,3R) diastereoselectivity in the reactions of new type of (S)-Ni(II) complexes constitute an improvement over the previously reported 1.7/1 ratio.","PeriodicalId":23438,"journal":{"name":"Ukr. Bioorg. Acta 2021, Vol. 16, N1","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89456341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-06-30DOI: 10.15407/bioorganica2021.01.018
S. Holota
In the present work, the synthesis of pyrazoline-thiazolidin-4-one hybrids and their pharmacological properties are described. The structure of compounds is characterized using 1H, 13C NMR, and LC-MS spectra. The antioxidant (DPPH assay), antimicrobial (Gram-positive bacterium Lactobacillus plantarum, Gram-negative bacterium Escherichia coli, and yeasts Candida albicans, MIC determination), redox (cyclic voltammetry) as well as herbicidal activity (against grass species Agrostis stolonifera) of compounds have been studied. All derivatives have demonstrated radical scavenging activity with IC50 values in the range from 4.67-7.12 mM in the DPPH test. The tested compounds presented very low antimicrobial and herbicidal activity and no redox peaks were observed in the cyclic voltammetry studies.
{"title":"Synthesis of novel pyrazoline-thiazolidin-4-one hybrids and evaluation their biological activity","authors":"S. Holota","doi":"10.15407/bioorganica2021.01.018","DOIUrl":"https://doi.org/10.15407/bioorganica2021.01.018","url":null,"abstract":"In the present work, the synthesis of pyrazoline-thiazolidin-4-one hybrids and their pharmacological properties are described. The structure of compounds is characterized using 1H, 13C NMR, and LC-MS spectra. The antioxidant (DPPH assay), antimicrobial (Gram-positive bacterium Lactobacillus plantarum, Gram-negative bacterium Escherichia coli, and yeasts Candida albicans, MIC determination), redox (cyclic voltammetry) as well as herbicidal activity (against grass species Agrostis stolonifera) of compounds have been studied. All derivatives have demonstrated radical scavenging activity with IC50 values in the range from 4.67-7.12 mM in the DPPH test. The tested compounds presented very low antimicrobial and herbicidal activity and no redox peaks were observed in the cyclic voltammetry studies.","PeriodicalId":23438,"journal":{"name":"Ukr. Bioorg. Acta 2021, Vol. 16, N1","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74056127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-06-30DOI: 10.15407/bioorganica2021.01.025
I. Semenyuta, M. Trush, D. Hodyna, M. Kachaeva, L. Metelytsia, V. Brovarets
The previously established in vitro high antimicrobial potential of triphenylphosphonium salts (TPPs) against bacterial (Staphylococcus aureus ATCC 25923 and multi-drug resistant (MDR)) and fungal (Candida albicans ATCC 10231 and MDR) strains made it possible to propose a molecular mechanism of action of these compounds associated with transglycosylase (TG) activity. The hypothesis was based on the well-known literature data on TPPs as inhibitors of S. aureus TG. The created homology model of TG C. albicans is optimal in terms of such quality indicators as GMQE (0.61), ERRAT (overall quality factor 95.904) and Ramachandran plot analysis (90% amino acid residues in the favored regions). Molecular docking of the most active ligands 1a-d, 3c into the active center of the created homology C. albicans TG model demonstrated the formation of stable ligand-protein complexes with binding energies in the range from -8.9 to -9.7 kcal/mol due to the various types of interactions. An important role in complex formation belongs to amino acid residues TYR307, TYR107, GLU275, ALA108 and PRO136. The presented qualitative homologous model of C. albicans TG can be used to search and create new agents with a dual mechanism of antimicrobial action. 1,3-oxazol-4-yltriphenylphosphonium salts 1a-d, 3c perform the perspective objects for further study as antimicrobials against infectious MDR pathogens.
{"title":"In vitro and in silico study of 1,3-oxazol-4-yltriphenylphosphonium salts as potential inhibitors of Candida albicans transglycosylase","authors":"I. Semenyuta, M. Trush, D. Hodyna, M. Kachaeva, L. Metelytsia, V. Brovarets","doi":"10.15407/bioorganica2021.01.025","DOIUrl":"https://doi.org/10.15407/bioorganica2021.01.025","url":null,"abstract":"The previously established in vitro high antimicrobial potential of triphenylphosphonium salts (TPPs) against bacterial (Staphylococcus aureus ATCC 25923 and multi-drug resistant (MDR)) and fungal (Candida albicans ATCC 10231 and MDR) strains made it possible to propose a molecular mechanism of action of these compounds associated with transglycosylase (TG) activity. The hypothesis was based on the well-known literature data on TPPs as inhibitors of S. aureus TG. The created homology model of TG C. albicans is optimal in terms of such quality indicators as GMQE (0.61), ERRAT (overall quality factor 95.904) and Ramachandran plot analysis (90% amino acid residues in the favored regions). Molecular docking of the most active ligands 1a-d, 3c into the active center of the created homology C. albicans TG model demonstrated the formation of stable ligand-protein complexes with binding energies in the range from -8.9 to -9.7 kcal/mol due to the various types of interactions. An important role in complex formation belongs to amino acid residues TYR307, TYR107, GLU275, ALA108 and PRO136. The presented qualitative homologous model of C. albicans TG can be used to search and create new agents with a dual mechanism of antimicrobial action. 1,3-oxazol-4-yltriphenylphosphonium salts 1a-d, 3c perform the perspective objects for further study as antimicrobials against infectious MDR pathogens.","PeriodicalId":23438,"journal":{"name":"Ukr. Bioorg. Acta 2021, Vol. 16, N1","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74302899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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