Identification of the protease inhibitor miraziridine A in the Red sea sponge Theonella swinhoei

BACKGROUND: Miraziridine A, a natural peptide isolated from a marine sponge, is a potent cathepsin B inhibitor with a second-order rate constant of 1.5 × 10(4) M(-1) s(-1). In the present study, miraziridine A was isolated from the Red Sea sponge Theonella swinhoei on the basis of chromatographic and spectrometric techniques. We conclude that T. swinhoei from the Red Sea represents an alternative source of the aziridinylpeptide miraziridine A to the previously identified Theonella mirabilis from Japan. We confirmed that the metabolite is produced by marine sponges from different geographical locations. CONTEXT: Marine sponges have been proven to be a rich source of secondary metabolites exhibiting a huge diversity of biological activities, including antimicrobial, antitumor and immunomodulatory activities. Theonella species (order Lithistida, Demospongiae) have been shown to be a source of anti-protease and anti-HIV secondary metabolites. AIMS: To identify the protease inhibitor mirazirine A in the marine sponge Theonella swinhoei. MATERIAL AND METHODS: The marine sponge Theonella swinhoei was collected by SCUBA diving in the Red Sea in Eilat (Israel). Sponge material was lyophilized and further extracted successively with cyclohexane, dichloromethane and methanol to obtain three crude extracts. LC-MS analysis was performed to confirm the presence of Miraziridine A in the dichloromethane fraction. RESULTS: In the present study, miraziridine A was isolated from the Red Sea sponge T. swinhoei on the basis of chromatographic and spectrophotometric techniques. CONCLUSIONS: We conclude that T. swinhoei from the Red Sea represents an alternative source of the aziridinylpeptide miraziridine A to the previously identified Theonella mirabilis from Japan.