Macrolactone Nuiapolide, Isolated from a Hawaiian Marine Cyanobacterium, Exhibits Anti-Chemotactic Activity

Abstract

A new bioactive macrolactone, nuiapolide (1) was identified from a marine cyanobacterium collected off the coast of Niihau, near Lehua Rock. The natural product exhibits anti-chemotactic activity at concentrations as low as 1.3 μM against Jurkat cells, cancerous T lymphocytes, and induces a G2/M phase cell cycle shift. Structural characterization of the natural product revealed the compound to be a 40-membered macrolactone with nine hydroxyl functional groups and a rare tert-butyl carbinol residue.

Palstimolide A: A Complex Polyhydroxy Macrolide with Antiparasitic Activity

“…Various NMR experiments and solvent systems were employed to solve the structure of 1, including the LR-HSQMBC that allows the detection of 4-, 5-, and even 6-bond long-range n J CH heteronuclear couplings [17] as well as 1D TOCSY with different mixing times. Using this expanded NMR data set, palstimolide A (1) was characterized as possessing seven contiguous 1,5-diols (or diol equivalents) and a tert-butyl substituent (Figure 1), and belonging to a small group of cyanobacterial polyhydroxy macrolides that includes bastimolide A (2) and B [6,7], nuiapolide (3) [9], and amantelides A (4) and B (5) [8]. All of these macrolides share a 40-membered ring with several hydroxy groups, a tert-butyl moiety, and an α,β-unsaturated carboxyl group (Figure 1).…”

“…Figure 1. Structure of palstimolide A (1) together with the related cyanobacterial 40-membered polyhydroxy macrolides bastimolide A [6], amantelides A and B [8], and nuiapolide [9]. [6], amantelides A and B [8], and nuiapolide [9].…”

“…Structure of palstimolide A (1) together with the related cyanobacterial 40-membered polyhydroxy macrolides bastimolide A [6], amantelides A and B [8], and nuiapolide [9]. [6], amantelides A and B [8], and nuiapolide [9]. In-depth analysis of the standard 2D-NMR data together with more specific NMR experiments, such as the LR-HSQMBC [17] and utilization of different solvent systems, allowed elucidation of the planar structure of palstimolide A (1).…”

“…In general, this class of polyhydroxy macrolides shows a broad range of biological activity, such as antimalarial, antiparasitic, antifungal, and chemotactic activity [6,[8][9][10][11]19,20]. The cytotoxic activity of members of this class is moderate-to-weak (IC 50 s of 0.87 to around 12 µM, with amantelide A being the most cytotoxic; cytotoxic activity for nuiapolide was not reported as a pure compound, however, the crude extract showed no cytotoxic activity at 25 µg/mL).…”

“…These carbon-chain compounds show a high diversity in their skeleton architectures along with complex spatial configurations. Examples of macrolides from Cyanobacteria include bastimolide A and B [6,7], amantelides A and B [8], nuiapolide [9], caylobolide A and B [10,11], swinholide A [12], phormidolide [13], cyanolide A [14], and palmyrolide [15].…”