194737-10-5

Upstream product

• 338-69-2 D-Alanine 
• 1531602-01-3 xenoamicin A 
• 98873-83-7 (+)-trienomycin A 
• 1394140-15-8 luminmycin C 

Relevant academic research and scientific papers

Ansamycins with Antiproliferative and Antineuroinflammatory Activity from Moss-Soil-Derived Streptomyces cacaoi subsp. asoensis H2S5

Three new 21-membered macrocyclic benzenoid ansamycins, trienomycins J-L (1-3), together with seven known analogues, trienomycins A-G (4-10), were isolated from liquid culture of the moss soil-derived actinomycete Streptomyces cacaoi subsp. asoensis H2S5. The structures of the new compounds were elucidated by extensive NMR spectroscopic analysis and HRESIMS data. The absolute configurations of trienomycins were established by Marfey's method. Antiproliferative assays showed that compound 1 had the greatest activity against HepG2 cells, with an IC50 value of 0.1 μM. The induction of apoptosis of HepG2 cells by 1 was investigated by flow cytometry and evaluation of nuclear morphology. In addition, all of the compounds inhibited nitric oxide production with IC50 values of 0.02 to 8.3 μM, and compounds 1, 4, and 7 were the most potent inhibitors. These findings will facilitate the development of new antineuroinflammatory agents.

Anti-MRSA actinomycins D1-D4 from the marine sponge-associated Streptomyces sp. LHW52447

Actinomycins D1?D4 (1–4), four new D-type actinomycin analogues, were isolated from the fermentation broth of a strain of marine sponge-associated Streptomyces sp. LHW52447, together with actinomycin D (5). The structures of 1?4 were

Coculture of a Pathogenic Actinomycete and Animal Cells to Produce Nocarjamide, a Cyclic Nonapeptide with Wnt Signal-Activating Effect

A coculture method with a pathogenic actinomycete of the genus Nocardia and an animal cell line was designed to reconstruct and emulate the initial infection state, and a new cyclic nonapeptide, named nocarjamide (1), was obtained by coculture of Nocardia tenerifensis IFM 10554T and the mouse macrophage-like cell line J774.1 in a modified Czapek-Dox medium. Nocarjamide (1) exhibited Wnt signal-activating effects.

Chemical constituents isolated from Antarctic marine-derived Aspergillus sp. SF-5976 and their anti-inflammatory effects in LPS-stimulated RAW 264.7 and BV2 cells

Three new benzaldehydes (1–3) and two new dioxopiperazine alkaloids (4 and 5), along with 23 known constituents, were isolated from Antarctic marine-derived Aspergillus sp. SF-5976. Their structures were determined by spectroscopic and chemical methods. Among them, 20 compounds showed inhibitory effects toward lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7 macrophages with IC50 values of 7.3–77.4 μM, while 22 compounds did in BV2 microglia with those of 4.6–72.3 μM. Furthermore, the effects of the newly isolated compounds on LPS-stimulated inducible NO synthase (iNOS) expression were investigated, and 1–3, and 5 inhibited iNOS in RAW 264.7 cells, while 1–5 did in BV2 cells. Also, 1–3 and 5 inhibited LPS-induced prostaglandin E2 production with IC50 values of 9.1–66.8 μM in RAW 264.7 macrophages by suppressing cyclooxygenase-2 (COX-2), while in BV2 microglia, 1–5 showed activities with those of 2.8–49.4 μM.

Neopeapyran, an unusual furo[2,3b]pyran analogue and turnagainolide C from a soil Streptomyces sp. S2236

Neopeapyran (1), an unusual furo[2,3b]pyran analogue, together with a new cyclopeptide, turnagainolide C (2), were isolated from Streptomyces sp. S2236 associated with the rhizosphere soil of Panax notoginseng. The planar structure and relative configuration of neopeapyran (1) were elucidated on the basis of spectroscopic techniques, while the absolute configuration was determined by TDDFT calculation. The absolute configuration of turnagainolide C (2) was determined by partial hydrolysis, together with the advanced Marfey's method and spectroscopic analysis. The antimicrobial activities of these two compounds were also investigated.

New cytotoxic callipeltins from the Solomon Island marine sponge Asteropus sp.

Four new callipeltin A derivatives (N–Q) have been isolated from the Solomon Island marine sponge Asteropus sp. Their structures were established by spectroscopic techniques followed by acid hydrolysis and derivatisation of the free amino acids, and subsequent LCMS analysis of the derivatives. The compounds were evaluated for their activity against cancer cell lines A2058 (melanoma), HT-29 (colorectal adenocarcinoma) and MCF-7 (breast adenocarcinoma) and non-malignant MRC-5 fibroblast cells. While the acyclic callipeltins P and Q were inactive the cyclic callipeltins N and O showed significant cytotoxicity against all exposed cell lines with IC50values as low as 0.16?μM confirming the role of cyclic configuration in biological activity.

Application of 3D NMR for Structure Determination of Peptide Natural Products

Despite the advances in NMR, structure determination is often slow and constitutes a bottleneck in natural products discovery. Removal of this bottleneck would greatly improve the throughput for antibiotic discovery as well as other therapeutic areas. Overall, faster structure methods for structure determination will serve the natural products community in a broad manner. This report describes the first application of 3D NMR for elucidation of two microbially produced peptide natural products with novel structures. The methods are cost-effective and greatly improve the confidence in a proposed structure.

Structure and biosynthesis of xenoamicins from entomopathogenic xenorhabdus

During the search for novel natural products from entomopathogenic Xenorhabdus doucetiae DSM17909 and X. mauleonii DSM17908 novel peptides named xenoamicins were identified in addition to the already known antibiotics xenocoumacin and xenorhabdin. Xenoamicins are acylated tridecadepsipeptides consisting of mainly hydrophobic amino acids. The main derivative xenoamicin A (1) was isolated from X. mauleonii DSM17908, and its structure elucidated by detailed 1 D and 2 D NMR experiments. Detailed MS experiments, also in combination with labeling experiments, confirmed the determined structure and allowed structure elucidation of additional derivatives. Moreover, the xenoamicin biosynthesis gene cluster was identified and analyzed in X. doucetiae DSM17909, and its participation in xenoamicin biosynthesis was confirmed by mutagenesis. Advanced Marfey's analysis of 1 showed that the absolute configuration of the amino acids is in agreement with the predicted stereochemistry deduced from the nonribosomal peptide synthetase XabABCD. Biological testing revealed activity of 1 against Plasmodium falciparum and other neglected tropical diseases but no antibacterial activity.

Luminmycins A-C, cryptic natural products from Photorhabdus luminescens identified by heterologous expression in Escherichia coli

The 18 kb silent luminmycin biosynthetic pathway from Photorhabdus luminescens was cloned into a vector by using the newly established linear-linear homologous recombination and successfully expressed in Escherichia coli. Luminmycins A-C (1-3) were isolated from the heterologous host, and their structures were elucidated using 2D NMR spectroscopy and HRESIMS. Luminmycin A is a deoxy derivative of the previously reported glidobactin A, while luminmycins B and C most likely represent its acyclic biosynthetic intermediates. Compound 1 showed cytotoxicity against the human colon carcinoma HCT-116 cell line with an IC50 value of 91.8 nM, while acyclic 2 was inactive at concentrations as high as 100 μg/mL.

Callyaerins A-F and H, new cytotoxic cyclic peptides from the Indonesian marine sponge Callyspongia aerizusa

Bioassay guided fractionation of the EtOAc fraction of the sponge Callyspongia aerizusa yielded seven new cytotoxic cyclic peptides callyaerins A-F (1-6) and H (8). Their structures were determined using extensive 1D ( 1H, 13C and DEPT) and 2D (COSY, HMQC, HMBC, TOCSY, and ROESY) NMR and mass spectral (ESI and HRESI-TOF) data. All compounds were cyclic peptides containing ring systems of 5-9 amino acids and side chains of 2-5 amino acids in length. An unusual (Z)-2,3-diaminoacrylic acid unit provided the template for ring closure and afforded the linkage to the peptidic side chain which was always initiated with a proline moiety. All peptides contained three or more proline residues and the remaining residues were predominantly hydrophobic residues with all amino acids present in the l form. Callyaerins A-F (1-6) and H (8) showed biological activity in antibacterial assays and in various cytotoxicity assays employing different tumour cell-lines (L5178Y, HeLa, and PC12). Callyaerins E (5) and H (8) exhibited strong activity against the L5178Y cell line with ED50 values of 0.39 and 0.48 μM, respectively. On the other hand, callyaerin A (1) showed strong inhibitory properties towards C. albicans.