Discovery of Primaquine–Indole Carboxamides with Cancer-Cell-Selective Antiproliferative Activity

Indole carboxylic acids are endogenous tryptophan metabolites that have demonstrated a variety of bioactivities, including anticancer effects. Specifically, indole acetic acid (IAA) elicits anticancer activity when combined with ultraviolet B or reactive oxygen species (ROS) generators. Primaquine (PQ) is an approved drug which elicits antimalarial activity through ROS generation. We investigated the effects of ICA, IAA, PQ, their combination and PQ-indole carboxamide conjugates on the viability of selected cancer cell lines. We identified PQ-indole carboxamide <b>2</b> which elicited more potent antiproliferative effects than PQ and ICA/PQ combination. Our data revealed that compound <b>2</b> derived a significant part of its antiproliferative effect from ROS generation.