Synthesis and Structure−Activity Relationship Study of Lamellarin Derivatives

Abstract

Ten derivatives (3-12) of marine alkaloid lamellarin D (1) were synthesized and evaluated for cytotoxicity against a HeLa cell line in an effort to examine their structure-activity relationships. It appeared that the hydroxyl groups at positions C-8 and C-20 of 1 were important structural requirements for cytotoxic activity, while the hydroxyl group at C-14 and the two methoxy groups at C-13 and C-21 were not necessary for the activity.

Marine Natural Products as Models to Circumvent Multidrug Resistance

“…Lamellarins were isolated from many marine organisms such as a prosobranch mollusk (Lamellaria sp.) [35,95], an ascidian (Daphniphyllum chartaceum), a sponge (Dendrilla cactos), and unidentified ascidians [35]. More than 50 lamellarins have been described and mainly differ in the number and position of hydroxyl and methoxy groups on the common chromenoindoles I scaffold (Figure 8) [96].…”

Diketopiperazine Alkaloids from a Deep Ocean Sediment Derived Fungus Penicillium sp.

“…The structure of 3 was established ( Fig. 1), and named brevicompanine D. The MOM group is a common protective group for amines, 6) alcohols, 7) and phenols 8) in organic synthesis but the MOM ether or MOM amine groups are quite rare in natural products. 9,10) Compound 4, named brevicompanine E, was obtained as a colorless powder.…”

Synthesis and Biological Activity of Lamellarin Alkaloids: An Overview

“…Since then, several detailed works on the cytotoxicity of these alkaloids, including their antiproliferative effects, have appeared. 8,9,11,12,14,16,21,33,85,91,92 In 1996, Quesada and co-workers (Table 6). Among the compounds tested, lamellarins D-triacetate, K, K-triacetate, M, and N-triacetate were highly active towards a variety of cell lines and especially P388 (murine leukemia), A549 (human lung carcinoma), HT29 (human colon carcinoma), and MEL28 (human melanoma) cells.…”

“…In particular, Ishibashi and Iwao were the first to attempt to establish the SAR of lamellarins. 21 They investigated the effect of individual hydroxyl and methoxy substituents on the cytotoxicity of lamellarin D towards HeLa cells (Table 8). Removing the C20 hydroxyl group (compound 221) and masking the C8 hydroxyl group as a methyl ether (compound 222, lamellarin ) resulted in a significant decrease in activity for lamellarin D, indicating that these two hydroxyl groups are essential for this activity.…”