Theophylline-7-acetic acid derivatives with amino acids as anti-tuberculosis agents.

Abstract

A series of amides were synthesized by condensation of theophylline-7-acetic acid and eight commercially available amino acid methyl ester hydrochlorides. Consecutive hydrolysis of six of the amido-esters resulted in the formation of corresponding amido-acids. The newly synthesized compounds were evaluated for their in vitro activity against Mycobacterium tuberculosis H37Rv. The activity varied depending on the amino acid fragments and in seven cases exerted excellent values with MICs 0.46-0.26 μM. Assessment of the cytotoxicity revealed that the compounds were not cytotoxic against the human embryonal kidney cell line HEK-293T. The theophylline-7-acetamides containing amino acid moieties appear to be promising lead compounds for the development of antimycobacterial agents.

• Authors: Yulian Voynikov, Violeta Valcheva, Georgi Momekov, Plamen Peikov, Georgi Stavrakov
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 24 Issue 14 Pg. 3043-5 (Jul 15 2014) ISSN: 1464-3405 [Electronic] England
• PMID: 24878196 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ltd. All rights reserved.

Chemical References

• Amino Acids
• Antitubercular Agents
• Theophylline
• acefylline

Topics

• Amino Acids (chemistry)
• Antitubercular Agents (chemical synthesis, chemistry, pharmacology)
• Dose-Response Relationship, Drug
• HEK293 Cells
• Humans
• Microbial Sensitivity Tests
• Molecular Structure
• Mycobacterium tuberculosis (drug effects)
• Structure-Activity Relationship
• Theophylline (analogs & derivatives, chemical synthesis, chemistry, pharmacology)