Synthesis and Biological Assessment of New Thiazoles for Mycobacterial Infections and Biofilm Disruption

Sixteen thiazoles, of which nine are unprecedented substances (<b>11</b>, <b>12</b>, <b>15</b>, <b>16</b>, <b>17</b>, <b>19</b>, <b>20</b>, <b>23</b>, and <b>24</b>), were obtained by a cyclocondensation reaction between a thioamide and an α-bromoketone, via Hantzsch synthesis. All thiazoles (<b>11</b>-<b>26</b>), along with four thiosemicarbazone derivatives (<b>7</b>-<b>10</b>) and their precursors (<b>1</b>-<b>6</b>), were evaluated for their activity against <i>Mycobacterium</i> species <i>Mycobacterium abscessus</i>, <i>Mycobacterium massiliense</i>, <i>Mycobacterium fortuitum</i>, and <i>Mycobacterium smegmatis</i>, as well as for their antibiofilm properties. Among them, compounds <b>7, 8</b>, <b>14</b>, <b>17</b>, <b>18</b>, <b>19</b>, <b>20</b>, and <b>21</b> showed promising results in minimum inhibitory concentration (MIC) assays, demonstrating bactericidal activity within 48 h. Moreover, all these compounds inhibited biofilm formation. Notably, the unprecedented thiazole <b>17</b>, along with <b>18</b> (MIC = 36 μmol L^-1) and <b>21</b> (MIC = 65 μmol L^-1), exhibited the lowest MIC values against all tested species, outperforming the reference drugs. Furthermore, these compounds showed a high degree of selectivity toward mycobacterial cells, as confirmed by cytotoxicity assays using peripheral blood mononuclear cells (PBMC) and Vero cells. These findings highlight the strong antimycobacterial potential of the new thiazole derivatives, warranting further investigation.