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Chem Biol Drug Des. 2016 Mar;87(3):335-41. doi: 10.1111/cbdd.12676. Epub 2015 Nov 23.

Design, Synthesis, and Antimycobacterial Activity of Novel Theophylline-7-Acetic Acid Derivatives With Amino Acid Moieties.

Author information

1
Faculty of Pharmacy, Medical University of Sofia, 2 Dunav St., Sofia, 1000, Bulgaria.
2
Institute of Microbiology, Bulgarian Academy of Sciences, 26 Akad. Bonchev St., Sofia, 1113, Bulgaria.
3
Institute of Organic Chemistry, Bulgarian Academy of Sciences, 9 Acad. Bonchev St., Sofia, 1113, Bulgaria.

Abstract

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 Mycobacterium tuberculosis H37Rv. 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.

KEYWORDS:

antimycobacterial activity; discriminant analysis; drug design; theophylline-7-acetic acid derivatives; tuberculosis

PMID:
26502828
DOI:
10.1111/cbdd.12676
[Indexed for MEDLINE]

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