Indole alkaloids from two cultured cyanobacteria, Westiellopsis sp. and Fischerella muscicola

Abstract

Chemical investigation of two cultured cyanobacteria, Westiellopsis sp. (SAG strain number 20.93) and Fischerella muscicola (UTEX strain number LB1829) led to the isolation of three hapalindole-type alkaloids, namely hapalindole X (1), deschloro hapalindole I (2), and 13-hydroxy dechlorofontonamide (3), along with ten known indole alkaloids (hapalindoles A, C, G, H, I, J, and U, hapalonamide H, anhydrohapaloxindole A, and fischerindole L) and fischerellins A and B. The structures were determined by a combination of spectroscopic analyses mainly based on 1D and 2D NMR and HRESIMS data. Selected compounds were evaluated for cytotoxicity and exhibited weak to moderate cytotoxicity against HT-29, MCF-7, NCI-H460, SF268, and IMR90 cells. All compounds, except hapalindole C, were evaluated for 20S proteasome inhibition and displayed either weak or no inhibition at 25 μg/mL. Selected compounds were also evaluated for antimicrobial activity, and hapalindoles X (1) and A, and hapalonamide H showed potent activity against both M. tuberculosis and C. albicans with MIC values ranging from 0.6 to 2.5 μM.

Plant-Derived Antimicrobials: Insights into Mitigation of Antimicrobial Resistance

“…However, alkaloids are not widely used for disease therapy because most of the compounds mentioned exhibit carcinogenic properties and may cause severe toxicity to humans [94][95]. Chelerythrine of the group isoquinoline and hapalindole of the group indole are a few exceptions which exhibit antimicrobial activity against drug resistant strains such as towards P. aeruginosa at low dosages but indicate no toxicity in Vero cells [96][97].…”

Hapalindoles from the Cyanobacterium Hapalosiphon sp. Inhibit T Cell Proliferation

“…Several strains of the family Hapalosiphonaceae produce indole alkaloids [8]. The major classes of these indole alkaloids include hapalindoles, ambiguines, fischerindoles, and welwitindolinones, of which more than 80 variants have been described in the literature [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24]. They share several common motifs: an indole or oxindole core, a cyclohexane fused to that core, an isonitrile or isothiocyanate functional group, a chlorine substituent, or an additional ring [25].…”

Anti-infective Natural Products from Cyanobacteria

“…Recently, it has been found that malyngolide interferes with bacterial quorum sensing (see section "Compounds interfering with bacterial quorum sensing"). The hapalindoles are a large compound family of related indole alkaloids that were first found in Hapalosiphon species [68][69][70], and were later also isolated from Fischerella [71,72] and Westelliopsis [72]. Hapalindoles show activity against a range of microorganisms including S. aureus, B. subtilis, Salmonella gallinarum, and E. coli [73].…”

“…Interestingly, the various hapalindole congeners feature highly differing activity against a panel of microorganisms. The most potent compound, hapalindole A (2), shows MICs at sub-µM concentrations [72]. While having high antibacterial activity, they later have also been shown to be moderately cytotoxic [72] and highly insecticidal [74].…”

“…The most potent compound, hapalindole A (2), shows MICs at sub-µM concentrations [72]. While having high antibacterial activity, they later have also been shown to be moderately cytotoxic [72] and highly insecticidal [74]. Their mode of action against eukaryotic cells is likely based on the modulation of sodium channels [75].…”