T- and B-cell immunosuppressive activity of novel α-santonin analogs with humoral and cellular immune response in Balb/c mice

Abstract

In continuation of our endeavours to synthesize immunosuppressive agents from α-santonin, we report herein the design and synthesis of a new series of α-santonin derived O-aryl/aliphatic ether, ester and amide analogs and the evaluation of their immunosuppressive activities. The <i>in vitro</i> studies led to several analogs with significant immunosuppressive effects by inhibiting ConA and LPS stimulated T- and B-cell proliferation in a dose dependent manner. The more significant compounds <b>4d</b>, <b>4e</b>, <b>4f</b>, <b>4h</b>, <b>6a</b> and <b>6b</b> displayed potent inhibitory activity on the mitogen-induced T- and B-cell proliferation in comparison to α-santonin <b>1</b>. Compound <b>4e</b> displayed stupendous <i>in vitro</i> immunosuppressive effects with ∼80% suppression of B and ∼75% suppression of T lymphocyte proliferation, respectively<i>.</i> The <i>in vivo</i> investigation on BALB/c mice revealed that non-cytotoxic compound <b>4e</b> suppresses both humoral and cellular immunity.