Promises of the Unprecedented Aminosterol Squalamine

Abstract

Squalamine, a water-soluble cationic steroid that was originally isolated during the 1990s from the dogfish Squalus acanthias, has begun to attract attention due to its significant antimicrobial activities against fungi, Gram-positive and Gram-negative bacteria. Additionally, this unusual sulfated aminosterol could be a very promising leader of a new class of drugs in the antiangiogenic, anticancer and antiviral fields. In this chapter, a current overview is provided of all the potentialities of this remarkable aminosteroid and its mimics in human disease treatment.The squalamine story began in late July 1989, when Dr M. Zasloff was invited to speak about magainin antibiotic peptides at Mount Desert Island Marine Biological Laboratory j 265

6-Polyaminosteroid Squalamine Analogues Display Antibacterial Activity against Resistant Pathogens

“…In recent years, a wide variety of low-molecular-weight antibiotics have been isolated from various animal species [6]. Among the strategies envisioned in our laboratory for the search of new host-defense agents, squalamine 1 and trodusquemine 2 (Figure 1) were identified as the first natural aminosterols from the dogfish shark, Squalus acanthias, exhibiting potent antimicrobial activities against MDR bacterial strains [7][8][9].…”

“…However, avoiding a future in which bacteria are once again widespread killers requires more than one approach, among them: the rational use of antibiotics in health care and veterinary medicine, improved techniques for developing new drugs, and new perspectives on how to live with the infectious creatures with which we share the planet In recent years, a wide variety of low-molecular-weight antibiotics have been isolated from various animal species [6]. Among the strategies envisioned in our laboratory for the search of new host-defense agents, squalamine 1 and trodusquemine 2 (Figure 1) were identified as the first natural aminosterols from the dogfish shark, Squalus acanthias, exhibiting potent antimicrobial activities against MDR bacterial strains [7][8][9]. Due to the difficulty of obtaining squalamine from natural sources, many synthetic methods have been performed using expensive starting materials [10].…”

Antibiofilm and Antivirulence Properties of 6-Polyaminosteroid Derivatives against Antibiotic-Resistant Bacteria

“…In 1993, squalamine 1 and trodusquemine 2 (Figure 1) were identified as the first natural aminosterols from the dogfish shark, Squalus acanthias, to exhibit potent antimicrobial activities against both Gram-positive and Gram-negative MDR bacterial species [12,13].…”

“…In 1993, squalamine 1 and trodusquemine 2 (Figure 1) were identified as the first natural aminosterols from the dogfish shark, Squalus acanthias, to exhibit potent antimicrobial activities against both Gram-positive and Gram-negative MDR bacterial species [12,13]. Since then, polyaminosterol derivatives have been designed and evaluated for their antimicrobial activities, particularly due to their original mechanism of action [13,14].…”

From Marine Metabolites to the Drugs of the Future: Squalamine, Trodusquemine, Their Steroid and Triterpene Analogues

“…The goal of this review is to systematize the information available in the literature (up to 2021 with impact up to the most recent years) on the chemistry and biological activity of steroid polyamines, including their influence on the synthesis, properties, and perspectives of terpenoids with polyamine fragments. Despite the fact that many works have been devoted to the chemistry and pharmacology of steroid polyamines, including reviews [11,12,[31][32][33][34][35][36][37][38][39][40][41][42], until now the scientific literature has not summarized information on complete syntheses, various modifications and biological activity of steroid polyamines. The goal of this review is to systematize the information available in the literature (up to 2021 with impact up to the most recent years) on the chemistry and biological activity of steroid polyamines, including their influence on the synthesis, properties, and perspectives of terpenoids with polyamine fragments.…”