Bacterial strains isolated from attine ants showed activity against the insect specialized fungal pathogen
Escovopsis
and also against the human protozoan parasite
Leishmania donovani
. The bioassay guided fractionation of extracts from cultures of
Streptomyces
sp. ICBG292, isolated from the exoskeleton of
Cyphomyrmex
workers, led to the isolation of Mer-A2026B (
1
), piericidin-A
1
(
2
) and nigericin (
3
). Nigericin (
3
) presented high activity against intracellular amastigotes of
L
.
donovani
(IC
50
0.129 ± 0.008 μM).
Streptomyces puniceus
ICBG378, isolated from workers of
Acromyrmex rugosus rugosus
, produced dinactin (
4
) with potent anti-
L
.
donovani
activity against intracellular amastigotes (IC
50
0.018 ± 0.003 μM). Compounds
3
and
4
showed good selectivity indexes, 88.91 and 656.11 respectively, and were more active than positive control, miltefosine. Compounds
1
–
4
were also active against some
Escovopsis
strains. Compounds
1
and
2
were also produced by
Streptomyces
sp. ICBG233, isolated from workers of
Atta sexdens
, and detected in ants’ extracts by mass spectrometry, suggesting they are produced in the natural environment as defensive compounds involved in the symbiotic interaction.
A screening was performed using nine marine-derived fungi as biocatalysts and the natural products (-)-ambrox® (1), (-)-sclareol (2), and (+)-sclareolide (3) in order to select the microorganisms able to catalyze the biooxidation of these compounds. It was observed that only the Aspergillus sydowii CBMAI 934, Botryosphaeria sp., Eutypella sp., and Xylaria sp. presented active oxidoreductases and catalyzed the regioselective hydroxylation in the natural products. The hydroxylated metabolites obtained were 1β-hydroxy-ambrox (1a) (14%, A. sydowii CBMAI 934); 3β-hydroxy-ambrox (1b) (17%, Botryosphaeria sp.; 11%, Eutypella sp.); 3β-hydroxy-sclareol (2a) (31%, Xylaria sp.; 69%, Botryosphaeria sp.; 55%, Eutypella sp.); 18-hydroxy-sclareol (2b) (10%, Xylaria sp.); and 3β-hydroxy-sclareolide (3a) (34%, Botryosphaeria sp.; 7%, Eutypella sp.). This is the first report of biohydroxylation of (-)-ambrox® (1), (-)-sclareol (2), and (+)-sclareolide (3) by whole mycelia of marine-derived fungi.
Marine natural products have currently been recognized as the most promising source of bioactive substances for drug discovery research. In this review, extraordinary metabolites from marine algae species are illustrated, as well as approaches for their isolation and determination of their biological properties and pharmaceutical potential. Furthermore, marine endophytic microorganisms (from marine algae) are presented as a new subject for extensive investigation to find novel natural products, which make them a potentially rich and innovative source for new drug candidates.
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