New diketopiperazine derivatives from a deep-sea-derived Nocardiopsis alba SCSIO 03039

Abstract

The strain SCSIO 03039 was isolated from a sediment sample in the Indian Ocean and was characterized as a Nocardiopsis alba species on the basis of its 16S rRNA gene sequence. Seven diketopiperazines (DKPs), including two new DKPs nocazines D (2a) and E (2b), and five known DKPs (1, 3-6), were isolated from N. alba SCSIO 03039, along with two known compounds 2-methoxy-1,4-naphthoquinone (7) and 1-hydroxy-4-methoxy-2-naphthoic acid (8). Their structures were elucidated by mass and NMR spectroscopic analyses. The structure of methoxyneihumicin (1), previously proposed in a conference poster lacking publicly available experimental data, was validated for the first time by detailed NMR analyses and X-ray diffraction study. The two enantiomers nocazines D (2a) and E (2b) were isolated as a mixture. Compounds 3 and 4 were only known as synthetic compounds before. Methoxyneihumicin (1) exhibited in vitro cytotoxicities against MCF-7 and SF-268 with IC₅₀ values of 4.6 and 12.7 μM, respectively, better than those of 6 (22.0 and 20.6 μM). The other compounds showed less pronounced cytotoxities against three tested human cancer cell lines and no compounds displayed antibacterial activities toward four indicator strains.

The tRNA-Dependent Biosynthesis of Modified Cyclic Dipeptides

“…In two recent studies, four formerly unknown highly modified CDPs, together with three known and highly similar compounds, could be isolated from Nocardiopsis dassonvillei and Nocardiopsis alba [56,57]. The authors were focused on their isolation and structure elucidation and were not concerned about their biosynthetic origins.…”

Antibacterial and Cytotoxic New Napyradiomycins from the Marine-Derived Streptomyces sp. SCSIO 10428

“…A number of structurally unique natural products with antitumor [3,4], antiinfective [5], and antimalarial bioactivities [6], have been discovered from marine-derived actinomycetes. Our recent efforts on marine-derived actinomycetes also led to the isolation of structurally diverse novel natural products with antibacterial, antitumor, and antimalarial bioactivities [7,8,9,10,11,12,13,14,15,16,17]. …”

Isomethoxyneihumicin, a new cytotoxic agent produced by marine Nocardiopsis alba KM6-1

“…nov 18 and methoxyneihumicin (3) produced by deep-sea-derived N. alba SCSIO 03039. 7 These diketopiperazinesrelated compounds exhibited cytotoxicity against KB (HeLa-derived cells), 19 MCF-7 (human breast adenocarcinoma cells), NCI-H460 (human non-small cell lung cancer cells) and SF-268 (human glioma cells). 7 In the present study, isomethoxyneihumicin was found to arrest Jurkat cells at the G2/M phase without cytotoxic effects until 12 h, and then exhibited cytotoxicity against Jurkat cells.…”

“…7 Biological properties Effects of isomethoxyneihumicin and methoxyneihumicin on the Jurkat cell cycle. The effects of isomethoxyneihumicin (1 and 2) and 3 on the cell cycle of Jurkat cells at 3,12 and 20 h were investigated using flow cytometry (Figure 3).…”

“…A new compound designated isomethoxyneihumicin (1 and 2) was isolated along with known methoxyneihumicin (3) 7 from the culture broth of strain KM6-1 under natural seawater-containing conditions ( Figure 1). Isomethoxyneihumicin was found to be a mixture of lactam-lactim tautomers 1 and 2.…”