루파리엘롤라이드 유도체의 분리,합성과 항균효과 평가

Abstract

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 A (PLA ), 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 = 0.002 mg/mL), compared to that of the natural product (MIC > 0.064 mg/mL). Also, N-pyridinyl pyridazinone analogue exhibited selective anti-cancer activity against A375SM with an EC50 value of 0.0063 mM/mL (luffariellolide, EC50 = 0.024 mg/mL), while luffariellolide showed non-selective cytotoxicity against most of cancer cell lines.bitory activity against phospholipase A (PLA ), 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 = 0.002 mg/mL), compared to that of the natural product (MIC > 0.064 mg/mL). Also, N-pyridinyl pyridazinone analogue exhibited selective anti-cancer activity against A375SM with an EC50 value of 0.0063 mM/mL (luffariellolide, EC50 = 0.024 mg/mL), while luffariellolide showed non-selective cytotoxicity against most of cancer cell lines.