Based on the marine natural products piperafizine B, X334 and our previously reported compound 4m, fourteen novel 3,6-diunsaturated 2,5-diketopiperazine (2,5-DPK) derivatives (1-2, 4-6, 8-16), together with two known ones (3 and 7), were designed and synthesized as anticancer agents against cell lines A549 and Hela. The MTT assay results showed that the derivatives 6, 8-12 and 15 had moderate to good anticancer capacities with the IC50 values ranging from 0.7 to 8.9 μM. Among them, compound 11 with naphthalen-1-ylmethylene and 2-methoxybenzylidene functions at the 3- and 6-positions of 2,5-DPK ring, respectively, displayed good inhibitory activities to both cancer cells A549 (IC50 = 1.2 μM) and Hela (IC50 = 0.7 μM). It could also induce apoptosis and obviously block the cell cycle progression at G2/M phase in both cells at 1.0 μM. The electron withdrawing functions might not be favorable for the derivatives with high anticancer activities. Additionally, compared to piperafizine B and X334, these semi-N-alkylated derivatives have high liposolubilities (> 1.0 mg•mL-1). Compound 11 can be further developed aiming to the discovery of novel anticancer candidate.

2,5-Dihydroxyacetophenone (DHAP) is an active compound obtained from Radix Rehmanniae Preparata, which is widely used as a herbal medicine in many Asian countries. DHAP has been found to possess anti-inflammatory, anti-anxiety, and neuroprotective qualities. For the present study, we evaluated the anti-cancer effects of DHAP on multiple myeloma cells. It was discovered that DHAP downregulated the expression of oncogenic gene products like Bcl-xl, Bcl-2, Mcl-1, Survivin, Cyclin D1, IAP-1, Cyclin E, COX-2, and MMP-9, and upregulated the expression of Bax and p21 proteins, consistent with the induction of G2/M phase cell cycle arrest and apoptosis in U266 cells. DHAP inhibited cell proliferation and induced apoptosis, as characterized by the cleavage of PARP and the activation of caspase-3, caspase-8, and caspase-9. Mitogen-activated protein kinase (MAPK) pathways have been linked to the modulation of the angiogenesis, proliferation, metastasis, and invasion of tumors. We therefore attempted to determine the effect of DHAP on MAPK signaling pathways, and discovered that DHAP treatment induced a sustained activation of JNK, ERK1/2, and p38 MAPKs. DHAP also potentiated the pro-apoptotic and anti-proliferative effects of bortezomib in U266 cells. Our results suggest that DHAP can be an effective therapeutic agent to target multiple myeloma.

Hexane is a solvent used extensively in the food industry for the extraction of various products such as vegetable oils, fats, flavours, fragrances, colour additives or other bioactive ingredients. As it is classified as a "processing aid", it does not have to be declared on the label under current legislation. Therefore, although traces of hexane may be found in final products, especially in processed products, its presence is not known to consumers. However, hexane, and in particular the n-hexane isomer, has been shown to be neurotoxic to humans and has even been listed as a cause of occupational diseases in several European countries since the 1970s. In order to support the European strategy for a toxic-free environment (and toxic-free food), it seemed important to collect scientific information on this substance by reviewing the available literature. This review contains valuable information on the nature and origin of the solvent hexane, its applications in the food industry, its toxicological evaluation and possible alternatives for the extraction of natural products. Numerous publications have investigated the toxicity of hexane, and several studies have demonstrated the presence of its toxic metabolite 2,5-hexanedione (2,5-HD) in the urine of the general, non-occupationally exposed population. Surprisingly, a tolerable daily intake (TDI) has apparently never been established by any food safety authority. Since hexane residues are undoubtedly found in various foods, it seems more than necessary to clearly assess the risks associated with this hidden exposure. A clear indication on food packaging and better information on the toxicity of hexane could encourage industry to switch towards one of the numerous other alternative extraction methods already developed.

2,5-Di(hydroxymethyl)furan (DHMF) is a high-value chemical block than can be synthesized from 5-hydroxymethylfurfural (HMF), a platform chemical that results from the dehydration of biomass-derived carbohydrates. In this work, the HMF biotransformation capability of different Fusarium species was evaluated and F. striatum was selected to produce DHMF. The effects of the inoculum size, glucose concentration and pH of the media over DHMF production were evalu-ated by a 23 factorial design. A substrate feeding approach was found suitable to overcome the toxicity effect of HMF towards the cells when added at high concentrations (>75 mM). The pro-cess was successfully scaled-up at bioreactor scale (1.3 L) with excellent DHMF production yields (95%) and selectivities (98%). DHMF was purified from the reaction media with high recovery and purity by organic solvent extraction with ethyl acetate.

Leishmaniasis remains a significant global health concern, with current treatments relying on outdated drugs associated with high toxicity, lengthy administration, elevated costs, and drug resistance. Consequently, the urgent need for safer and more effective therapeutic options in leishmaniasis treatment persists. Previous research has highlighted selenium compounds as promising candidates for innovative leishmaniasis therapy. In light of this, a library of 10 selenium-containing diverse compounds was designed and evaluated in this study. The compounds were subjected to screening against L. amazonensis promastigotes, and their cytotoxicity was assessed in NIH/3T3 cells. Among the tested compounds, MRK-106 and MRK-108 displayed the highest potency against L. amazonensis promastigotes while demonstrating reduced cytotoxicity. Notably, MRK-106 and MRK-108 exhibited IC50 values of 3.97 µM, 4.23 µM, respectively, and most of the tested compounds showed low cytotoxicity in NIH/3T3 cells (CC50 > 200 µM). Although these results are promising, additional investigations focusing on intracellular amastigotes are required to determine the antileishmanial activity of the compounds. In conclusion, the identified selenium-containing compounds hold considerable potential as antileishmanial drug candidates and warrant further exploration in subsequent studies. These findings represent a significant step towards the development of safer and more effective therapies for leishmaniasis, addressing the pressing need for novel and improved treatments.

Two novel core-shell composites SiO2@PMDA-Si-Tb, SiO2@PMDA-Si-Tb-phen with SiO2 as the core and terbium organic complex as the shell, were successfully synthesized. The terbium ion was coordinated with organic ligand forming terbium organic complex in the shell layer. The bi-functional organosilane ((HOOC)2C6H2(CONH(CH2)3Si(OCH2CH3)3)2 (abbreviated as PMDA-Si) was used as the first ligand and phen as the second ligand. Furthermore, the silica-modified SiO2@PMDA-Si-Tb@SiO2, SiO2@PMDA-Si-Tb-phen@SiO2 core-shell-shell composites were also synthesized by sol–gel chemical route. An amorphous silica shell was coated around the SiO2@PMDA-Si-Tb and SiO2@PMDA-Si-Tb-phen core-shell composites. The core-shell and core-shell-shell composites both exhibited excellent luminescence in solid state. The luminescence of core-shell-shell composites was stronger than that of core-shell composites. Meanwhile, an improved luminescence stability property for the core-shell-shell composites was found in the aqueous solution. The core-shell-shell composites exhibited bright luminescence, high stability, long lifetime, and good solubility, which may present potential applications in the field of bio-medical.

Streptomyces, being one of the most promising genera due to its ability to synthesize a variety of bioactive secondary metabolites of pharmaceutical interest, here studied in relation to its genomic and metabolomic potential. Coinciding with the increase in sequenced data, mining of bacterial genomes for biosynthetic gene clusters (BGCs) has become a routine component of natural product discovery. Herein, we describe the isolation and characterization of a Streptomyces tendae VITAKN with quorum sensing inhibitory activity (QSI) that was isolated from southern coastal parts of India. The nearly complete genome consists of 8,621,231bp with a GC content of 72.2%. Utilizing the BiG-SCAPE-CORASON platform, a sequence similarity network predicted from this strain was evaluated through sequence similarity analysis with the MIBiG database and existing 3,365 BGCs predicted by antiSMASH analysis of publicly available complete Streptomyces genomes. Crude extract analyzed on LC-HRMS/MS and Global Natural Product Social Molecular Networking (GNPS) online workflow using dereplication resulted in the identification of cyclic dipeptides (2,5-diketopiperazines, DKPs) in the extract, which are known to possess QSI activity. Our results highlight the potential use of genomic mining coupled with LC-HRMS/MS and bionformatic tools (GNPS) as a potent approach for metabolome studies in discovering novel QSI lead compounds. This study also provides the biosynthetic diversity of these BGCs and an assessment of the predicted chemical space yet to be discovered.

a Special Issue of Microorganisms devoted to ‘Microbial Biocatalysis and Biodegradation’ would be incomplete without some form of acknowledgement of the many important roles that dioxygen-dependent enzymes (principally mono- and dioxygenases) play in relevant aspects of biooxygenation. This is reflected by the multiple strategic roles that dioxygen -dependent microbial enzymes play both in generating valuable synthons for chemoenzymatic synthesis, and in facilitating key reactions that drive the global geochemical Carbon Cycle. A useful insight into this relationship can be gained by reviewing the evolution of the current status of 2,5-diketocamphane 1,2-monooxygenase (EC 1.14.14.108) from camphor-grown Pseudomonas putida ATCC 17453. Over the last sixty years, the perceived nature of this monooxygenase has transmogrified significantly. Commencing in the 1960s, extensive initial studies consistently reported that the enzyme was a monomeric true flavoprotein dependent on both FMNH₂ and nonheme iron as bound cofactors. However, over the last decade all those criteria have changed absolutely, and the enzyme is currently acknowledged to be a metal ion-independent homodimeric flavin-dependent two-component monooxygenase deploying FMNH₂ as a cosubstrate. That transition is a paradigm of the ever evolving nature of scientific knowledge.