Shimpei Sumimoto

Isolation and Total Synthesis of Hoshinolactam, an Antitrypanosomal Lactam from a Marine Cyanobacterium

In the search for new antiprotozoal substances, hoshinolactam, an antitrypanosomal lactam, was isolated from a marine cyanobacterium. The gross structure was elucidated by spectroscopic analyses, and the absolute configuration was determined by the first total synthesis. Hoshinolactam showed potent antitrypanosomal activity with an IC50 value of 3.9 nM without cytotoxicity against human fetal lung fibroblast MRC-5 cells (IC50 > 25 μM).

Kohamamides A, B, and C, Cyclic Depsipeptides from an Okeania sp. Marine Cyanobacterium

Kohamamides A, B, and C (1-3), new cyclic depsipeptides that belong to the kulolide superfamily, were isolated from an Okeania sp. marine cyanobacterium. Their structures were elucidated by spectroscopic analyses and degradation reactions. Kohamamide B (2) exhibited moderate cytotoxicity against HL60 cells. Although many natural products in the kulolide superfamily have been isolated from cyanobacteria collected in various parts of the world, kohamamides 1-3 are the first members to be isolated from the East Asian marine environment. In addition, unlike other members of this superfamily, kohamamides 1-3 contain a Leu residue adjacent to the Pro residue, rather than another lipophilic amino acid.

Three new malyngamides from the marine cyanobacterium moorea producens

Three new compounds of the malyngamide series, 6,8-di-O-acetylmalyngamide 2 (1), 6-O-acetylmalyngamide 2 (2), and N-demethyl-isomalyngamide I (3), were isolated from the marine cyanobacterium Moorea producens. Their structures were determined by spectroscopic analysis and chemical derivatization and degradation. These compounds stimulated glucose uptake in cultured L6 myotubes. In particular, 6,8-di-O-acetylmalyngamide 2 (1) showed potent activity and activated adenosine monophosphate-activated protein kinase (AMPK).

Isolation of Jahanene and Jahanane, and Total Synthesis of the Jahanyne Family

Two new jahanyne analogues, jahanene and jahanane, highly N-methylated lipopeptides, were isolated from a marine cyanobacterium Okeania sp., and their structures were determined by NMR and MS. In addition, we achieved total syntheses of the jahanyne family and assessed their activities. The resulting growth-inhibitory activity of jahanyne was nearly one-tenth of the previously reported activity. Furthermore, we found that the degree of unsaturation at the terminus of the fatty acid moiety affected the growth-inhibitory activity against human cancer cells.

Biseokeaniamides A, B, and C, Sterol O-Acyltransferase Inhibitors from an Okeania sp. Marine Cyanobacterium

Biseokeaniamides A, B, and C (1-3), structurally novel sterol O-acyltransferase (SOAT) inhibitors, were isolated from an Okeania sp. marine cyanobacterium. Their structures were elucidated by spectroscopic analyses and degradation reactions. Biseokeaniamide B (2) exhibited moderate cytotoxicity against human HeLa cancer cells, and compounds 1-3 inhibited both SOAT1 and SOAT2, not only at an enzyme level but also at a cellular level. Biseokeaniamides (1-3) are the first linear lipopeptides that have been shown to exhibit SOAT-inhibitory activity.

Ypaoamides B and C, Linear Lipopeptides from an Okeania sp. Marine Cyanobacterium

Two new pyrrolinone-containing lipopeptides, ypaoamides B (1) and C (2), were isolated from an Okeania sp. marine cyanobacterium collected in Okinawa. Their structures were determined by spectroscopic analysis and Marfeys analysis of acid hydrolysates. Ypaoamides B (1) and C (2) stimulated glucose uptake in cultured rat L6 myotubes. In particular, ypaoamide B (1) showed potent activity and activated AMP-activated protein kinase.

Izenamides A and B, Statine-Containing Depsipeptides,and an Analogue from a Marine Cyanobacterium

Izenamides A, B, and C (1-3), new linear depsipeptides, were isolated from a taxonomically distinct marine cyanobacterium. Izenamides A and B contain a statine moiety [(3 S,4 S)-4-amino-3-hydroxy-6-methylheptanoic acid] and inhibited the activity of cathepsin D, an aspartic peptidase. Meanwhile, izenamides did not show growth-inhibitory activity against HeLa, HL60, or MCF-7 cells at up to 10 μM.