Amantelides A and B, Polyhydroxylated Macrolides with Differential Broad-Spectrum Cytotoxicity from a Guamanian Marine Cyanobacterium

Abstract

Cytotoxicity-guided fractionation of a Guamanian cyanobacterial collection yielded the new compounds amantelides A (1) and B (2). These polyketides are characterized by a 40-membered macrolactone ring consisting of a 1,3-diol and contiguous 1,5-diol units and a tert-butyl substituent. Amantelide A (1) displayed potent cytotoxicity with submicromolar IC₅₀ against HT29 colorectal adenocarcinoma and HeLa cervical carcinoma cell lines. Acetylation of the hydroxy group at C-33 in 2 caused a close to 10-fold decrease in potency. Exhaustive acetylation of the hydroxy groups abrogated the antiproliferative activity of amantelide A (1) by 20-67-fold. Further bioactivity assessment of 1 against bacterial pathogens and marine fungi indicated a broad spectrum of bioactivity.

Figure 1

Partial structure of amantelide A (1).

Figure 2

Fragmentation pattern of amantelide A (1) induced by ESI-MS (negative mode).

Figure 3

Predicted ¹³C NMR shifts of 1,3-diols based on Kishi’s Universal NMR database and corresponding chemical shifts of the 1,3-diol moiety in amantelide A (1) and caylobolide B. ¹³C NMR shifts for C-7 and C-9 in 1 are in accordance with syn configuration and comparable to those of caylobolide B.