Coibacins A-D, antileishmanial marine cyanobacterial polyketides with intriguing biosynthetic origins

Abstract

Four unsaturated polyketide lactone derivatives, coibacins A-D, were isolated from a Panamanian marine cyanobacterium, cf. Oscillatoria sp. The two different types of termini observed in these co-occurring metabolites, either a methyl cyclopropyl ring as seen in curacin A or a methyl vinyl chloride similar to that observed in the jamaicamides, suggest an intriguing flexibility in the "beta branch" forming biosynthetic process. The coibacins possess selective antileishmanial activity as well as potent anti-inflammatory activity.

Figure 1

Structures of coibacins A-D (1-4) with two other marine cyanobacterial metabolites of related biosynthetic origin, curacin A (5) and jamaicamide A (6).

Figure 2

Transcription of pro-inflammatory genes after treatment with coibacin A (1) at 10 μg/mL (bars represent the mean ± standard deviation; N = 3. *P-value < 0.05 compared to LPS treatment alone. **P-value < 0.01 compared to LPS treatment alone).