Design, Synthesis and in vitro Controlled Release of New Adamantanodiarylketone Antimycobacterials

What is it about?

In the present investigation, the synthesis, the biology and the development of matrix tablet formulations for the in vitrocontrolled release of new adamantane diarylketone antimycobacterial derivatives, is presented. In the skeleton of the new compounds, a diarylketone, functionalized by a 2-hydroxypropylenoxy- 3-butylamine, a 2-hydroxypropylenoxy-3-hexylamine and a 1-(2-hydroxyoctyl)piperidin-4-yl moiety, is incorporated at the C-1 adamantane position. The new derivatives were tested against the H37Rv mycobacterium tuberculosis strain and 1exhibited satisfactory activity. In view of their lipophilic character, it was intriguing to examine their in vitro dissolution profile in buffer solutions simulating the gastric and intestinal environments. To this end, matrix tablets of the most active compound, {4-[(adamantan-1-yl) phenyl-4-(3-(butylamino)-2-hydroxypropoxy)]phenyl}methanone (A), incorporating the appropriate excipients, were prepared using the direct compression method. The preliminary test results show that its dissolution profile is in alignment with the desired pattern for the per os administration of tuberculocidal agents.

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Why is it important?

The presence of the adamantane core and the benzophenone moiety in one scaffold was found to lead to promising antituberculars. The most active analogue A, although quite lipophilic showed a controlled release profile, which is in alignment with the desired pattern for the per os administration of tuberculocidal agents.

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