What question did this study set out to answer?

To evaluate the in vitro antimycobacterial activity of 2,4-diamino-5-methyl-5-deazapteridine derivatives against Mycobacterium avium complex and assess their selectivity against mycobacterial versus human dihydrofolate reductase.

October 1, 2000Antimicrobial Agents and ChemotherapyOpen Access

Antimycobacterial Activities of 2,4-Diamino-5-Deazapteridine Derivatives and Effects on Mycobacterial Dihydrofolate Reductase

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To evaluate the in vitro antimycobacterial activity of 2,4-diamino-5-methyl-5-deazapteridine derivatives against Mycobacterium avium complex and assess their selectivity against mycobacterial versus human dihydrofolate reductase.
Screened 77 deazapteridine derivatives bearing diverse chemical substitutions at positions 5 and 6 against Mycobacterium avium complex strains NJ168, NJ211, and NJ3404.
Measured minimum inhibitory concentrations via colorimetric Alamar Blue broth microdilution assays and determined 50% inhibitory concentrations against recombinant MAC and human dihydrofolate reductase.
Assayed intracellular antimycobacterial activity of a rationally designed derivative within a MAC-infected Mono Mac 6 monocytic cell line.
In total, 73 of 77 derivatives inhibited MAC NJ168 at concentrations ≤13 µg/ml, and 81% to 87% achieved MICs of ≤1.3 µg/ml across the evaluated strains.
Twenty-one derivatives demonstrated >100-fold greater selectivity against MAC recombinant dihydrofolate reductase relative to the human enzyme, governed by the bridge composition at position 6 and aryl substitutions.
A tailored derivative achieved significant intracellular antimycobacterial activity against MAC residing within Mono Mac 6 monocytic cells.

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Implication

In vitro study reveals selective inhibition of Mycobacterium avium complex dihydrofolate reductase by deazapteridines, indicating their potential as targeted antimycobacterial therapies.

Cite This Study

Suling et al. (2000) studied this question.

synapsesocial.com/papers/6a76266f7d7eb453cc708b3b https://doi.org/10.1128/aac.44.10.2784-2793.2000

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Implication

In vitro study reveals selective inhibition of Mycobacterium avium complex dihydrofolate reductase by deazapteridines, indicating their potential as targeted antimycobacterial therapies.

Antimycobacterial Activities of 2,4-Diamino-5-Deazapteridine Derivatives and Effects on Mycobacterial Dihydrofolate Reductase

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Discussion

Implication

Cite This Study

Antimycobacterial Activities of 2,4-Diamino-5-Deazapteridine Derivatives and Effects on Mycobacterial Dihydrofolate Reductase

Key Points

Discussion

Implication

Cite This Study

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