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 25μg/mL. Selected compounds were also evaluated for antimicrobial activity, and hapalindoles X (1) and A, and hapalonamide H showed potent activity against both Mycobacterium tuberculosis and Candida albicans with MIC values ranging from 0.6 to 2.5μM.
Highlights
As part of our ongoing collaborative natural product drug discovery project,[22] we evaluated organic extracts of cultured cyanobacteria for cytotoxicity using a set of human cancer cell lines designated HT-29, MCF-7, NCI-H460, and SF268 (CNS)
Selected compounds were evaluated for cytotoxicity against HT-29, MCF-7, NCI-H460, and SF268 (CNS) cancer cells, and IMR90 cells (Table 4)
Hapalindole X (1) displayed antimicrobial activities against both M. tuberculosis and C. albicans with MIC values of 2.5 μM and moderate cytotoxicity in the Vero cell assay with an IC50 value of 35.2 μM
Summary
More than 4000 strains of cyanobacteria (blue-green algae) have been studied to date, with more than 1000 secondary metabolites described.[1,2,3,4] This includes over 70 indole alkaloids from branched filamentous cyanobacteria belonging to the order Stigonematales.[5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21] These alkaloids include hapalindoles,[5,6,7,8,9] fischerindoles,[10,11,12] welwitindolinones,[11] ambiguines,[13,14,15,16,17] hapalindolinones,[18] hapaloxindoles,[19,20] and fontonamides.[19,20] All have polycyclic carbon skeletons derived from L-tryptophan and geraniol pyrophosphate and possess diverse biological activities, such as antibacterial, antifungal, and antialgal activities.[5, 10, 21]. As part of our ongoing collaborative natural product drug discovery project,[22] we evaluated organic extracts of cultured cyanobacteria for cytotoxicity using a set of human cancer cell lines designated HT-29 (colon), MCF-7 (breast), NCI-H460 (lung), and SF268 (CNS). Bioassay-guided fractionation led to isolation of hapalindole X (1) and deschloro hapalindole I (2) along with previously known hapalindoles A, C, G, H, I, J, and U, and hapalonamide H. The organic extract of Fischerella muscicola (UTEX LB1829) inhibited the growth of MCF-7, NCI-H460, and SF268 cells, and 13-hydroxy dechlorofontonamide (3) was isolated along with previously known hapalindoles A, H, I, and J, as well as fischerellins A and B. The three new hapalindole-type alkaloids were named hapalindole X (1), deschloro hapalindole I (2), and 13-hydroxy dechlorofontonamide (3) in line with the tradition used for previously reported hapalindole-type alkaloids from cyanobacteria (Figure 1). We present the isolation, structure elucidation, and bioactivity evaluation of these compounds
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