Isolation and biological evaluation of 8-epi-malyngamide C from the Floridian marine cyanobacterium Lyngbya majuscula

Abstract

A new stereoisomer of malyngamide C, 8-epi-malyngamide C (1), and the known compound lyngbic acid [(4E,7S)-7-methoxytetradec-4-enoic acid] were isolated from a sample of Lyngbya majuscula collected near Bush Key, Dry Tortugas, Florida. The structure of 1 was determined by NMR and MS experiments. The absolute configuration of 1 was determined by selective Mitsunobu inversion of C-8 to give malyngamide C, as determined by NMR, MS, and comparison of specific rotation. Both 1 and malyngamide C were found to be cytotoxic to HT29 colon cancer cells (IC(50) 15.4 and 5.2 microM, respectively) and to inhibit bacterial quorum sensing in a reporter gene assay.

Figure 1

Structures of 8-epi-malyngamide C (1) and lyngbic acid.

Figure 2

Comparison of ¹H NMR signal for H-8 in A) 8-epi-malyngamide C (1) and B) malyngamide C (400 MHz, CDCl₃).

Figure 3

Activity against the quorum sensing reporter pSB1075, which expresses LasR and responds to 3-oxo-C₁₂-HSL. (*) indicates reduction of luminescence with statistical significance of P < 0.05 (t-test) compared to untreated controls.

Scheme 1

Conversion of 1 to malyngamide C by Mitsunobu inversion. i) PPh₃, p-NBA, DEAD, THF, rt for 14 h, then 40 °C for 3 h; ii) K₂CO₃, rt for 1 h.