Squalamine is a natural aminosterol that has been discovered in the tissues of the dogfish shark (Squalus acanthias). Studies have previously demonstrated that this promoter compound and its derivatives exhibit potent bactericidal activity against Gram-negative, Gram-positive bacteria, and multidrug-resistant bacteria. The antibacterial activity of squalamine was found to correlate with that of other antibiotics, such as colistin and polymyxins. Still, in the field of microbiology, evidence has shown that squalamine and its derivatives have antifungal activity, antiprotozoa effect against a limited list of protozoa, and could exhibit antiviral activity against both RNA- and DNA-enveloped viruses. Furthermore, squalamine and its derivatives have been identified as being antiangiogenic compounds in the case of several types of cancers and induce a potential positive effect in the case of other diseases such as experimental retinopathy and Parkinson’s disease. Given the diverse effects of the squalamine and its derivatives, in this review we provide the different advances in our understanding of the various effects of these promising molecules and try to draw up a non-exhaustive list of the different mechanisms of actions of squalamine and its derivatives on the human organism and on different pathogens.
Squalamine and Derivatives | Structure | Pharmacological Activity | References |
---|---|---|---|
Squalamine | Antibacterial activity: Escherichia coli (ATCC 25922, ATCC 54127); Pseudomonas aeruginosa (ATCC 27853, strain PAO1, ATCC 1569, ATCC 15442); Staphylococcus aureus (ATCC 25923, ATCC 6538); Streptococcus pneumoniae (a clinical isolate); Acinetobacter baumannii Antifungal activity: Candida albicans (ATCC 10231, (ATCC 90028); Aspergillus niger (ATCC 16404); Candida glabrata (ATCC 90030); Candida krusei (ATCC 6258); Candida parapsilosis (ATCC 22019) Bloodstream yeast isolates: C. albicans; C. glabrata; C. guilliermondii; C. krusei; C. lusitaniae; C. parapsilosis; C. tropicalis, Cryptococcus neoformans; Trichophyton rubrum; T. mentagrophytes; T. soudanense; Microsporum canis; M. audouinii; M. persicolor; M. cookie; M. gypseum; Tinea capitis Antiviral activity: Dengue virus; Human hepatitis B virus; Human hepatitis δ-virus; Yellow fever virus; Eastern equine encephalitis virus; Murine cytomegalovirus Antiprotozoa activity: Trypanosoma brucei; Leishmania donovani Eucaryote cells: Eukaryote cell (Wehi-231 cells) Antiangiogenic activity: Chicken embryo; MCF-7 (Michigan Cancer Foundation-7); Human breast cancer cell line; Pancreatic (BxPC-3, MiaPaCa-2) and hepatic (HepG2, Huh7) cancer cells; Rat mammary carcinoma and a murine Lewis lung carcinoma; Xenograft models using the chemoresistant MV-522 human non-small cell lung carcinoma and the SD human neuroblastoma lines; PS120/NHE3 fibroblasts cells; Rat brain endothelial (RBE-4) cell; Rabbit VX2 tumor cells Clinical trials for cancer cases: Patients with advanced cancers: Patients with metastasis to the central nervous system; Patients with liver metastasis; Patients with a histologically confirmed diagnosis of nonleukemic malignancy refractory; Patients with advanced solid malignancies; Patients with advanced non-small cell lung cancer Parkinson’s disease: Effect on the gastrointestinal tract (constipation) and neuron motility Retinopathies: Rat choroidal neovascular membrane; Iris neovascularization in cynomolgus monkeys; Ocular neovascularization Clinical trials for Retinopathies: Patients with macular edema |
[5,8,9,11,15,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52] | |
Synthesized aminosterol derivatives (ASD) ASD 1 [7-(1,4-diaminobutane)-cholest-5-ene-3β-ol] |
Antibacterial activity: E. coli (ATCC 25922); P. aeruginosa (ATCC 27853); S. aureus (ATCC 25923); S. pneumoniae isolates Antifungal: C. albicans (ATCC 90028); C. glabrata (ATCC 90030); C. krusei (ATCC 6258); C. parapsilosis (ATCC 22019) Bloodstream yeast isolates: C. albicans; C. glabrata; C. guilliermondii, C. krusei; C. lusitaniae ; C. parapsilosis; C. tropicali; C. neoformans |
[8,18,20] | |
ASD 2 [7β-(1,4-diaminobutane)-cholestan-3β-ol] | Antibacterial activity: E. coli (ATCC 25922); P. aeruginosa (ATCC 27853); S. aureus (ATCC 25923); S. pneumoniae isolates |
[18,32] | |
3-amino- and polyaminosterol analogues of squalamine and trodusquemine 4b, 4e, 4n, 4r, 6b, 8b, 8c, 8d, 8e | Antibacterial activity: E. coli (ATCC 10536); S. aureus (ATCC 6538); Enterococcus faecalis (CIP 103015) Antifungal activity: C. albicans (ATCC 90029); C. tropicalis (CIP 2031); Saccharomyces cerevisiae (ATCC 28383) |
[53] | |
3, 20-amino- and polyaminosteroid analogues of squalamine and trodusquemine | Antibacterial activity: S. aureus; P. aeruginosa; Inquilinus limosus; Burkholderia cepacia |
[54] | |
Dimeric sterol-polyamine conjugates (2, 4a, 4b, 5, 6a, 6b, 6c, 7a, 7b) |
Antibacterial activity: E. coli (ATCC 25922 and ESBL clinical isolates); K. pneumoniae (clinical isolates); Acinetobacter spp. (clinical isolates); P. aeruginosa (clinical isolates); group A Streptococcus (clinical isolates); coag. neg. Staphylococcus (clinical isolates); S. aureus (A8115 MSSA, A8816 MRSA, A5948 MRSA 32); Enterococcus faecium (ATCC 29212, ATCC 51299, and clinical isolates) |
[17] | |
Squalamine Mimics: Head-to-Tail Dimeric SterolPolyamine Conjugates (1–8) |
Antibacterial activity: E. coli (ATCC 25922 and ESBL clinical isolates); K. pneumoniae (clinical isolates); Acinetobacter spp. (clinical isolates); P. aeruginosa (clinical isolates); E. faecalis (ATCC 29212, ATCC 51299, and clinical isolates); E. faecium (clinical isolates); S. aureus (ATCC 29213, MSSA, and MRSA clinical isolates); Coag. Neg. Staphylococcus (clinical isolates); Group A Streptococcus (clinical isolates) |
[55] | |
Squalamine mimics | Antibacterial activity: E. coli (ATCC 25922); K. pneumoniae (ATCC 13883); P. aeruginosa (ATCC 27853); E. faecalis (ATCC29212); S. aureus (ATCC 25923); S. pyogenes (ATCC 19615); Antifungal activity: C. albicans (ATCC 90028) |
[16] | |
Squalamine analogues | Antiprotozoa activity: Leishmania donovani |
[26] | |
NV669 | Antiangiogenic activity: Pancreatic (BxPC-3, MiaPaCa-2) and hepatic (HepG2, Huh7) cancer cells |
[39] |
This entry is adapted from the peer-reviewed paper 10.3390/microorganisms10061205