Lipoxygenases (LOXs) are a class of enzymes that catalyze the production of pro-inflammatory mediators, such as leukotrienes and lipoxins, via an arachidonic acid cascade as soon as they are released from the membrane phospholipids after tissue injury. In continuation of our efforts in search for new LOX inhibitors, a series of chlorophenyl-furfuryl-based 1,2,4-triazole derivatives were prepared and evaluated for their 15-LOX inhibitory activities. A simple precursor, 4-chlorobenzoic acid ( a ), was consecutively transformed into benzoate ( 1 ), hydrazide ( 2 ), semicarbazide ( 3 ), and N -furfuryl 5-(4-chlorobenzyl)-4 H -1,2,4-triazole ( 4 ), which when further merged with electrophiles ( 6a–o ) resulted in end products ( 7a–o ). The structural elucidations of the newly synthesized compounds ( 7a–o ) were carried out by Fourier transform infrared, 1 H-, 13 C NMR spectroscopy, EI-MS, and HR-EI-MS spectrometry. The inhibitive capability of compounds ( 7a–o ) on soybean 15-LOX was performed in vitro using the chemiluminescence method. The compounds 7k , 7o , 7m , 7b, and 7i demonstrated potent activities (IC 50 17.43 ± 0.38, 19.35 ± 0.71, 23.59 ± 0.68, 26.35 ± 0.62, and 27.53 ± 0.82 μM, respectively). These compounds revealed 79.5 to 98.8% cellular viability as measured by the MTT assay at 0.25 mM concentration. The structure-activity relationship (SAR) studies showed that the positions and the nature of substituents bonded to the phenyl ring are important in the determination of 15-LOX inhibitory activities. ADME, in silico, and density functional theory studies supported the evidence as yet another class of triazoles with potential lead properties in search for anti-LOX compounds with a safe gastrointestinal safety profile for various inflammatory diseases. Further work is in progress on the synthesis of more derivatives in search for anti-inflammatory agents.

The title compound, ircinianin, C25H32O4, belongs to the sesterterpene tetronic acid compound family and was isolated from the marine sponge Ircinia wistarii. These chemical scaffolds are pharmacologically relevant, since they represent a new class of glycine receptor modulators. The furan ring makes a dihedral angle of 35.14 (12)° to the 4-hydroxy-3-methylfuran-2(5H)-one ring. The crystal packing is characterized by intermolecular O—H...O hydrogen bonds, which generate [010] chains.

Lasso peptides are a class of ribosomally synthesized and post-translationally modified peptides (RiPPs) that feature an isopeptide bond and a distinct lariat fold. A growing number of secondary modifications have been described that further decorate lasso peptide scaffolds. Using genome mining, we have discovered a pair of lasso peptide biosynthetic gene clusters (BGCs) that include cytochrome P450 genes. Here, we report the structural characterization of two unique examples of (C-N) biaryl-containing lasso peptides. Nocapeptin A, from Nocardia terpenica, is tailored with Trp-Tyr crosslink while longipepetin A, from Longimycelium tulufanense, features Trp-Trp linkage. Besides the unusual bicyclic frame, longipepetin A receives an S-methylation by a new Met methyltransferase resulting in unprecedented sulfonium-bearing RiPP. Our bioinformatic survey revealed P450(s) and further maturating enzyme(s)-containing lasso BGCs awaiting future characterization.

Two new ircinianin-type sesterterpenoids, ircinianin lactone B and ircinianin lactone C (7 and 8), together with five known entities from the ircinianin compound family (1, 3–6) were isolated from the marine sponge Ircinia wistarii. Ircinianin lactones B and C (7 and 8) represent new ircinianin terpenoids with a modified oxidation pattern. Despite their labile nature, the structures could be established using a combination of spectroscopic data, including HRESIMS and 1D/2D NMR techniques, as well as computational chemistry and quantum-mechanical calculations. In a broad screening approach for biological activity, the class-defining compound ircinianin (1) showed moderate antiprotozoal activity against Plasmodium falciparum (IC50 25.4 μM) and Leishmania donovani (IC50 16.6 μM).