title: 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.affiliation: Faculty of Pharmacy, Medical University of Sofia, str. Dunav 2, Sofia 1000, Bulgaria.
authors.forename: Yulian
authors.initials: Y
authors.lastname: Voynikov
authors.affiliation: Institute of Microbiology, Bulgarian Academy of Sciences, Akad. Bonchev 26, Sofia 1113, Bulgaria.
authors.forename: Violeta
authors.initials: V
authors.lastname: Valcheva
authors.affiliation: Faculty of Pharmacy, Medical University of Sofia, str. Dunav 2, Sofia 1000, Bulgaria.
authors.forename: Georgi
authors.initials: G
authors.lastname: Momekov
authors.affiliation: Faculty of Pharmacy, Medical University of Sofia, str. Dunav 2, Sofia 1000, Bulgaria.
authors.forename: Plamen
authors.initials: P
authors.lastname: Peikov
authors.affiliation: Faculty of Pharmacy, Medical University of Sofia, str. Dunav 2, Sofia 1000, Bulgaria. Electronic address: gstavrakov@pharmfac.net.
authors.forename: Georgi
authors.initials: G
authors.lastname: Stavrakov
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D057809:HEK293 Cells; D006801:Humans; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D013329:Structure-Activity Relationship; D013806:Theophylline / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000596:Amino Acids; D000995:Antitubercular Agents; D013806:Theophylline; C019140:acefylline
keywords: Amides; Amino acids; Cytotoxicity; Purine; Tuberculosis; Xanthine