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1

α-Amino acid-derived 2-phenylimidazoles with potential antimycobacterial activity

100%

Cvejn D., Klimešová V., Bureš F.

Open Chemistry

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2012

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vol. 10

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issue 5

1681-1687

EN

α-Amino acid-derived 2-phenylimidazole derivatives were designed, synthesized, and further investigated as potential antimycobacterial agents. The synthesis of target imidazole derivatives involved the transformation of Cbz-protected α-amino acids (Ala, Val, Phe, Leu, iLe, and Pro) into α-diazoketones and α-bromoketones, respectively. Subsequent treatment of α-bromoketones with (4-nitro)benzamidine afforded imidazole derivatives bearing α-amino acid residue appended to the imidazole C4 and (4-nitro)phenyl ring in the position C2. Antimycobacterial activities of both series of compounds against M. tuberculosis, M. avium, and M. kansasii were screened and basic structure-activity relationships were further evaluated. [...]

2

Oxytocin analogues with amide groups substituted by tetrazole groups in position 4, 5 or 9

100%

Manturewicz M., Grzonka Z., Borovičková L., Slaninová J.

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2007

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vol. 54

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issue 4

805-811

EN

Eleven oxytocin analogues substituted in position 4, 5 or 9 by tetrazole analogues of amino acids were prepared using solid-phase peptide synthesis method and tested for rat uterotonic in vitro and pressor activities, as well as for their affinity to human oxytocin receptor. The tetrazolic group has been used as a bioisosteric substitution of carboxylic, ester or amide groups in structure-activity relationship studies of biologically active compounds. Replacement of the amide groups of Gln4 and Asn5 in oxytocin by tetrazole analogues of aspartic, glutamic and α-aminoadipic acids containing the tetrazole moiety in the side chains leads to analogues with decreased biological activities. Oxytocin analogues in which the glycine amide residue in position 9 was substituted by tetrazole analogues of glycine had diminished activities as well. The analysis of differences in rat uterotonic activity and in the affinity to human oxytocin receptors of analogues containing either an acidic 5-substituted tetrazolic group or a neutral 1,5- or 2,5-tetrazole nucleus makes it possible to draw some new conclusions concerning the role of the amide group of amino acids in positions 4, 5 and 9 of oxytocin for its activity. The data suggest that the interaction of the side chain of Gln4 with the oxytocin receptor is influenced mainly by electronic effects and the hydrogen bonding capacity of the amide group. Steric effects of the side chain are minor. Substitution of Asn5 by its tetrazole derivative gave an analogue of very low activity. The result suggests that in the interaction between the amide group of Asn5 and the binding sites of oxytocic receptor hydrogen bonds are of less importance than the spatial requirements for this group.

3

A theoretical antioxidant pharmacophore for natural hydroxycinnamic acids

75%

Szeląg M., Urbaniak A., Bluyssen H. A. R.

Open Chemistry

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2015

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vol. 13

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issue 1

EN

The structure-activity relationship analysis has been performed for trans- and cis-hydroxycinnamic acids, to determine their theoretical antioxidant pharmacophore. Based on the detailed conformational studies, the most stable rotamers have been selected. We have analyzed the descriptors of four antioxidant mechanisms important in free radical scavenging: hydrogen atom transfer, sequential proton loss electron transfer, single electron transfer - proton transfer and transition metal chelation, based on the B3LYP/6-311++G(2d,2p) calculations in vacuum and polar media. The results explain the activity difference between cinnamic acid and its derivatives. The descending order of antioxidant potential is as follows: caffeic > sinapinic ~ ferulic > p-coumaric > o-coumaric > m-coumaric ~ phenol. The results have shown that transisomers indicate higher reactivity than cis- and may be considered as good antioxidants. It has been determined that the highest antioxidant ability is related to the hydroxyl group in para position, supported by planar structure and stability of radical forms. π-Type delocalization of unpaired electron on aromatic ring, double bond and para O-atom is the key to radical stabilization. The ortho-dihydroxy substitution in benzene ring positively influences the ability to neutralize free radicals and makes caffeic acid the antioxidant pharmacophore of hydroxycinnamic acids.

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2 Open Chemistry

1 Acta Biochimica Polonica

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1 Bluyssen H. A. R.

1 Borovičková L.

1 Bureš F.

1 Cvejn D.

1 Grzonka Z.

1 Klimešová V.

1 Manturewicz M.

1 Slaninová J.

1 Szeląg M.

1 Urbaniak A.

α-Amino acid-derived 2-phenylimidazoles with potential antimycobacterial activity

Oxytocin analogues with amide groups substituted by tetrazole groups in position 4, 5 or 9

A theoretical antioxidant pharmacophore for natural hydroxycinnamic acids