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Design, Synthesis, and Antimycobacterial Activity of Novel Theophylline‐7‐Acetic Acid Derivatives With Amino Acid Moieties
Author(s) -
Stavrakov Georgi,
Valcheva Violeta,
Voynikov Yulian,
Philipova Irena,
Atanasova Mariyana,
Konstantinov Spiro,
Peikov Plamen,
Doytchinova Irini
Publication year - 2016
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12676
Subject(s) - antimycobacterial , theophylline , acetic acid , chemistry , combinatorial chemistry , stereochemistry , organic chemistry , pharmacology , mycobacterium tuberculosis , biology , tuberculosis , medicine , pathology
The theophylline‐7‐acetic acid (7‐ TAA ) scaffold is a promising novel lead compound for antimycobacterial activity. Here, we derive a model for antitubercular activity prediction based on 14 7‐ TAA derivatives with amino acid moieties and their methyl esters. The model is applied to a combinatorial library, consisting of 40 amino acid and methyl ester derivatives of 7‐ TAA . The best three predicted compounds are synthesized and tested against M ycobacterium tuberculosis H 37 R v. All of them are stable, non‐toxic against human cells and show antimycobacterial activity in the nanomolar range being 60 times more active than ethambutol.