Design,Synthesis, and Antimycobacterial Activity of Novel Theophylline‐7‐Acetic Acid Derivatives With Amino Acid Moieties |
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| Authors: | Georgi Stavrakov Violeta Valcheva Yulian Voynikov Irena Philipova Mariyana Atanasova Spiro Konstantinov Plamen Peikov Irini Doytchinova |
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| Affiliation: | 1. Faculty of Pharmacy, Medical University of Sofia, Sofia, Bulgaria;2. Institute of Microbiology, Bulgarian Academy of Sciences, Sofia, Bulgaria;3. Institute of Organic Chemistry, Bulgarian Academy of Sciences, Sofia, Bulgaria |
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| 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. |
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| Keywords: | antimycobacterial activity discriminant analysis drug design theophylline‐7‐acetic acid derivatives tuberculosis |
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