Abstract Five new abyssomicin monomers (1−5), three new abyssomicin dimers (6−8), as well as the known abyssomicin analogues (9−13), were obtained from the endophytic Streptomyces sp. ns5-4 isolated from the medicinal herb Polygonatum sibiricum. The chemical structures of these compounds were identified by the analysis of the NMR, MS, and ECD spectra. The neuroprotective activities of the isolates were evaluated by the MTT assay. Abyssomicin 7 (3) and 9-O-methylabyssomicin 7 (4) showed significant neuroprotective activities against glutamate-induced excitotoxicity in HT22 cells, with EC50 values of 2.98 and 0.49 μM, respectively. Furthermore, compounds 3 and 4 exhibited negligible cytotoxicities toward normal HT22 cells at a concentration of 200 μM.
Abstract Feeding m-phenylenediamine to Myrothecium verrucaria HPU-ZMN produced eight new phenylpyrrole derivatives, myrodiamines A−H (1−8). Compounds 2 and 5 were likely purification artifacts. In contrast to the monofunctional aniline precursors used previously, the bifunctional diamine is processed along two routes: both amino groups engage in pyrrole formation to give dipyrrole dimers 1−5 or one is cyclized while the other is acylated, affording monopyrrole amides 6−8. Structures were elucidated by 1D/2D NMR and HRESIMS. Compound 3 showed potent cytotoxicity against K562 cells (IC50 = 0.073 μM) and promising activity against NCI-H446, NCI-H446/EP, and MDA-MB-231 cells (IC50 = 0.26−0.51 μM).
Abstract Four new lipopeptides, erysiopeptides A−D, were isolated from the marine bacterium Vibrio sp. AFB22-4MB1. Their planar structures were elucidated on the basis of comprehensive spectroscopic analyses. A candidate biosynthetic gene cluster (BGC) for their production, encoding a non-ribosomal peptide synthetase, was identified in the genome sequence, and a corresponding biosynthetic proposal was developed. The absolute configurations of the component amino acids were established by advanced Marfey’s analysis and corroborated by bioinformatic predictions from the BGC. The stereochemistry of the β-hydroxyl group in the fatty chain was determined by derivatization of the hydrogenated product. Erysiopeptides exhibited moderate iron chelating as well as antibacterial activity against the Gram-positive bacterium Bacillus subtilis.
Abstract The NLRP3 inflammasome plays a central role in the innate immune response of inflammatory bowel disease (IBD), and its excessive activation drives the release of pro-inflammatory cytokines and compromises intestinal mucosal barrier integrity. In this study, the natural cycloheptapeptide unguisin E (1) was identified through anti-inflammatory screening of a marine-derived molecule library. To improve its anti-inflammatory potency, 1 was employed as a lead compound for structural modification at the C-2 position of the indole moiety via Suzuki coupling, affording a series of cycloheptapeptide derivatives (2−40). Among them, CHNQD-01024 (12) significantly inhibited IL-1β release from the NLRP3 inflammasome in THP-1 and J774A.1 cell lines at 0.4 μM, exhibiting inhibition potency comparable to the positive control MCC950 at 2 μM. In the DSS-induced colitis mouse model, CHNQD-01024 significantly ameliorated systemic inflammation, mitigated colonic tissue damage, and restored intestinal barrier function at doses of 5−15 mg/kg, with efficacy comparable to the first-line clinical drug 5-ASA at 50 mg/kg. Mechanistic studies showed that CHNQD-01024 suppressed NLRP3 inflammasome-associated inflammatory signaling, accompanied by the inhibition of NF-κB signaling and ROS production, reduced NLRP3 expression, and impaired ASC oligomerization. Taken together, these findings identify CHNQD-01024 as a promising marine fungal-derived anti-inflammatory lead suppressing NLRP3 inflammasome-associated signaling.
Abstract Four previously unreported glycosylated linear polyene polyketides, kofumicins A−D (1−4), were isolated from Kutzneria kofuensisNRRL 24061 and were found to inhibit Staphylococcus aureus growth. The kofumicins were identified from the crude extract using a bacterial activity metabolomics-guided approach, which employs split-flow HPLC-UV/MS to generate microtiter plate arrays enabling dereplication and bioactivity assessment prior to isolation. The structures were determined using NMR data, HR-ESI-MS, and biosynthetic gene cluster inference, establishing the kofumicins as new members of a family of glycosylated amphoteric linear polyene polyketides. Kofumicins A−C (1−3) share a conserved polyketide chain but differ in disaccharide composition and glycosidic regiochemistry, while kofumicin D (4) exhibits a truncated polyketide chain with a monosaccharide. Distance-constrained molecular dynamics calculations suggest that the kofumicins adopt a bent bolaamphiphilic conformation. Kofumicin C (3), bearing 6-deoxyglucose as the polyketide-linked sugar, was the most potent glycovariant tested, with MICs of 2−4 μg/mL against S. aureus strains including MRSA, while kofumicin B (2), bearing a glucose at the same position, exhibited MICs of 16−32 μg/mL. These results identify the C-6 substituent of the polyketide-linked sugar as an important determinant of antibacterial potency in this compound class.
