Luffariellolide, an anti-inflammatory sesterterpene, was originally isolated as a major metabolite from the hexane extract of the Palauan sponge Luffariella variabilis. Initially, luffariellolide has been reported to exhibit reversible inhibitory activity against phospholipase A2 (PLA2), which is a mediator for inflammation. During the course of our research to identify marine invertebrates producing pharmacologically useful metabolites, luffariellolide was isolated from the marine sponge Suberea sp., which was collected offshore of the Philippines. Chemical diversification on the g-hydroxylbutenolide core of luffariellolide revealed that pyridazinone-type derivatives can enhance the antimicrobial activity toward K. pneumonia up to 32 times (MIC = 2 mg/mL), compared to that of the natural product (MIC &gt; 64 mg/mL). Also, N-pyridinyl pyridazinone analogue exhibited selective anti-cancer activity against A375SM with an EC50 value of 6.3 mM/mL (luffariellolide, EC50 = 24 mg/mL), while luffariellolide showed non-selective cytotoxicity against most of cancer cell lines.

Isolation and synthesis of luffariellolide derivatives and evaluation of antibacterial activities against Gram-negative bacteria

256th National Meeting (2018)

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