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

Abstract

This review comprehensively describes the recent advances in the synthesis and pharmacological evaluation of steroid polyamines squalamine, trodusquemine, ceragenins, claramine, and their diverse analogs and derivatives, with a special focus on their complete synthesis from cholic acids, as well as an antibacterial and antiviral, neuroprotective, antiangiogenic, antitumor, antiobesity and weight-loss activity, antiatherogenic, regenerative, and anxiolytic properties. Trodusquemine is the most-studied small-molecule allosteric PTP1B inhibitor. The discovery of squalamine as the first representative of a previously unknown class of natural antibiotics of animal origin stimulated extensive research of terpenoids (especially triterpenoids) comprising polyamine fragments. During the last decade, this new class of biologically active semisynthetic natural product derivatives demonstrated the possibility to form supramolecular networks, which opens up many possibilities for the use of such structures for drug delivery systems in serum or other body fluids.

Design and synthesis of hybrid compounds as novel drugs and medicines

“…cholic acid type) conjugates display many exciting biological activities. 45 Squalamine analogues also demonstrate the possibility to form supramolecular networks, opening up many possibilities in their use in drug delivery systems in serum or other body uids. The research area of steroid polyamines, e.g., squalamine, trodusquemine, ceragenins, claramine, and their diverse analogues and derivatives, has been comprehensively reviewed.…”

“…The research area of steroid polyamines, e.g., squalamine, trodusquemine, ceragenins, claramine, and their diverse analogues and derivatives, has been comprehensively reviewed. 45 As well as an antibacterial, such compounds display antiviral, neuroprotective, antiangiogenic, antitumor, antiobesity and weight-loss activity, antiatherogenic, regenerative, and anxiolytic properties. We and others have shown that cholic acid and other bile acids act as a lipidic region, [46][47][48] so that aer the many phosphate negative charges along the DNA or siRNA drug have been neutralised by the polycationic polyamine region, the nucleic acid thereby being condensed, the formed nanoparticle is coated in the steroid lipid.…”

Alpha-Synuclein Aggregation Pathway in Parkinson’s Disease: Current Status and Novel Therapeutic Approaches

“…Alternatively, some natural steroid compounds have been reported to be useful α-Syn fibril disaggregators. Squalamine, steroid polyamine, and similar metabolites obtained from sharks were originally applied as anticancer and antibacterial agents [ 203 ], as well as in obesity treatment and tissue regeneration [ 204 ]. Squalamine’s proposed action mechanism relies on the displacement of α-Syn toxic forms at the plasma membrane.…”

Squalamine and Its Aminosterol Derivatives: Overview of Biological Effects and Mechanisms of Action of Compounds with Multiple Therapeutic Applications

“…Other compounds mimicking squalamine have been synthesized from a sterol precursor by attaching a polyamine side chain and by changing the nature of the sterol core, and the position of the polyamine side chain (Table 1) [16,17]. Research to date has shown that squalamine and its derivatives have an antibacterial activity and also have an effect on viruses, fungi, and on other important diseases such as cancers (lung, ovarian, brain) and neurodegenerative diseases [14]. The purpose of this review is to highlight the different advances in our understanding of the biological effects and mechanisms of actions of squalamine and its derivatives on the human organism.…”

“…Research to date has shown that squalamine and its derivatives have an antibacterial activity and also have an effect on viruses, fungi, and on other important diseases such as cancers (lung, ovarian, brain) and neurodegenerative diseases [14]. The purpose of this review is to highlight the different advances in our understanding of the biological effects and mechanisms of actions of squalamine and its derivatives on the human organism.…”