During the last three decades, secondary metabolites of marine origin have emerged as a significant source of bioactive compounds. Among the marine organisms explored, sponges offer a vast number of metabolites with unique structural diversity and a plethora of biological activities. Ageladine A, a fluorescent bromopyrrole alkaloid isolated from the marine sponge Agelas nakamurai, exhibited matrix metalloproteinase (MMP) inhibitory properties, as well as antiangiogenic activity. Due to this interesting biological profile, Ageladine A became, soon after its discovery, a target for total synthesis. In addition, a significant number of derivatives have been synthesized, and their biological activity was evaluated. The present review highlights all the successful efforts made towards the synthesis of Ageladine A. Furthermore, all the medicinal chemistry approaches to identify and assess new more potent inhibitors and to elucidate the structural features responsible for the activity are described. © 2023 by the author.