Synthesis, Anticancer and Antitubercular Properties of New Chalcones and Their Nitrogen-Containing Five-Membered Heterocyclic Hybrids Bearing Sulfonamide Moiety

Abstract

A new series of sulfonamides, <b>8a-b, 10, 12</b>, and <b>14a-b</b>, were synthesized by <i>N</i>-sulfonation reaction with sulfonyl chlorides <b>6a-b</b>. Five new series of chalcone-sulfonamide hybrids <b>(16-20)a-f</b> were prepared via Claisen-Schmidt condensation of the newly obtained sulfonamides with aromatic aldehydes <b>15a-f</b> in basic medium. Chalcones substituted with chlorine at position 4 of each series were used as precursors for the generation of their five-membered heterocyclic pyrazoline (<b>22-23)a-d</b>, (<b>24-25</b>)<b>a-b</b> and carbothioamide <b>27a-f</b> derivatives. The synthesized compounds were evaluated for their anticancer and antituberculosis activities. To determine their anticancer activity, compounds were screened against sixty human cancer cell lines at a single dose (10 μM). Compounds <b>17a-c</b> were highly active against LOX IMVI (melanoma), with IC₅₀ values of 0.34, 0.73 and 0.54 μM, respectively. Chalcone <b>18e</b> showed remarkable results against the entire panel of leukemia cell lines with IC₅₀ values between 0.99-2.52 μM. Moreover, compounds <b>20e</b> and <b>20f</b> displayed growth inhibition of <i>Mycobacterium tuberculosis</i> H37Rv at concentrations below 10 μM. Although they showed low selectivity in cytotoxicity tests against the Vero cell line, further optimization could advance the potential biological activity of the selected compounds.