Synthesis of new boswellic acid derivatives as potential antiproliferative agents

Abstract

In the current investigation, a series of heterocyclic derivatives of boswellic acids were prepared along with new monomers of 3-<i>O</i>-acetyl-11-keto-β-boswellic acid (AKBA, <b>1</b>) 11-keto-β-boswellic acid (KBA, <b>2</b>) and several new bis-AKBA and KBA homodimers and AKBA-KBA heterodimers. The effects of these compounds on the proliferation of different human cancer cell lines, viz., FaDu (pharynx carcinoma), A2780 (ovarian carcinoma), HT29 (colon adenocarcinoma), and A375 (malignant melanoma), have been evaluated. Thus, KBA homodimer <b>21</b> effectively inhibited the growth of FaDu, A2780, HT29, and A375 cells with EC₅₀ values below 9 μM. In addition, compounds <b>7</b>, <b>8</b>, <b>11</b>, <b>12</b>, <b>15</b>, <b>16,</b> and <b>17</b> also exhibited cytotoxic effects for A2780, HT29, and A375 cancer cells. In particular, the pyrazine analog <b>8</b> was highly cytotoxic for A375 cancer cells with an EC₅₀ value of 2.1 μM.