Title:Synthesis and Biological Evaluations of Granulatamide B and its
Structural Analogues
Volume: 31
Issue: 25
关键词:
颗粒酰胺B, n -脂肪酰基衍生物，抗氧化，抗增殖，抗菌，胚胎毒性。
摘要:
Background: While granulatamides A and B have been previously isolated,
their biological activities have been only partially examined. The aim of this study was
to synthesize granulatamide B (4b), a tryptamine-derivative naturally occurring in Eunicella
coral species, using the well-known procedure of Sun and Fürstner and its 12 structural
analogues by modifying the side chain, which differs in length, degree of saturation
as well as number and conjugation of double bonds.
Methods: The prepared library of compounds underwent comprehensive assessment for
their biological activities, encompassing antioxidative, antiproliferative, and antibacterial
properties, in addition to in vivo toxicity evaluation using a Zebrafish model. Compound
4i, which consists of a retinoic acid moiety, exhibited the strongest scavenging activity
against ABTS radicals (IC50 = 36 ± 2 μM). In addition, 4b and some of the analogues
(4a, 4c and 4i), mostly containing an unsaturated chain and conjugated double
bonds, showed moderate but non-selective activity with certain IC50 values in the range
of 20-40 μM.
Results: In contrast, the analogue 4l, a derivative of alpha-linolenic acid, was the least
toxic towards normal cell lines. Moreover, 4b was also highly active against Gram-positive
Bacillus subtilis with an MIC of 125 μM. Nevertheless, both 4b and 4i, known for
the best-observed effects, caused remarkable developmental abnormalities in the zebrafish
model Danio rerio.
Conclusion: Since modification of the side chain did not significantly alter the change
in biological activities compared to the parent compound, granulatamide B (4b), the substitution
of the indole ring needs to be considered. Our group is currently carrying out
new syntheses focusing on the functionalization of the indole core.
