Design, Synthesis, and Antimycobacterial Activity of Novel Theophylline-7-Acetic Acid Derivatives With Amino Acid Moieties.
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.
Faculty of Pharmacy, Medical University of Sofia, 2 Dunav St., Sofia, 1000, Bulgaria.
Georgi
G
Stavrakov
Institute of Microbiology, Bulgarian Academy of Sciences, 26 Akad. Bonchev St., Sofia, 1113, Bulgaria.
Violeta
V
Valcheva
Faculty of Pharmacy, Medical University of Sofia, 2 Dunav St., Sofia, 1000, Bulgaria.
Yulian
Y
Voynikov
Institute of Organic Chemistry, Bulgarian Academy of Sciences, 9 Acad. Bonchev St., Sofia, 1113, Bulgaria.
Irena
I
Philipova
Faculty of Pharmacy, Medical University of Sofia, 2 Dunav St., Sofia, 1000, Bulgaria.
Mariyana
M
Atanasova
Faculty of Pharmacy, Medical University of Sofia, 2 Dunav St., Sofia, 1000, Bulgaria.
Spiro
S
Konstantinov
Faculty of Pharmacy, Medical University of Sofia, 2 Dunav St., Sofia, 1000, Bulgaria.
Plamen
P
Peikov
Faculty of Pharmacy, Medical University of Sofia, 2 Dunav St., Sofia, 1000, Bulgaria.
Irini
http://orcid.org/0000-0002-1469-1768
I
Doytchinova
D000596:Amino Acids / Q000737:chemistry*; D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D015195:Drug Design; D006801:Humans; D008826:Microbial Sensitivity Tests; D013806:Theophylline / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D000596:Amino Acids; D000995:Antitubercular Agents; D013806:Theophylline
antimycobacterial activity; discriminant analysis; drug design; theophylline-7-acetic acid derivatives; tuberculosis