Organotin(IV) carboxylates are a class of compounds explored as alternatives to platinum-containing chemotherapeutics due to propitious in vitro and in vivo results, and distinct mechanisms of action. In this study, triphenyltin(IV) derivatives of non-steroidal anti-inflammatory drugs (indomethacin (HIND) and flurbiprofen (HFBP)) are synthesized and characterized, namely [Ph3Sn(IND)] and [Ph3Sn(FBP)]. The crystal structure of [Ph3Sn(IND)] reveals penta-coordination of the central tin atom with almost perfect trigonal bipyramidal geometry with phenyl groups in the equatorial positions and two axially located oxygen atoms belonging to two distinct carboxylato (IND) ligands leading to formation of a coordination polymer with bridging carboxylato ligands. Employing MTT and CV probes, the antiproliferative effects of both organotin(IV) complexes, indomethacin, and flurbiprofen were evaluated on different breast carcinoma cells (BT-474, MDA-MB-468, MCF-7 and HCC1937). [Ph3Sn(IND)] and [Ph3Sn(FBP)], unlike the inactive ligand precursors, were found extremely active towards all examined cell lines, demonstrating IC50 concentrations in the range of 0.076–0.200 µM. Flow cytometry was employed to examine the mode of action showing that neither apoptotic nor autophagic mechanisms were triggered within the first 48 h of treatment. However, both tin(IV) complexes inhibited cell proliferation potentially related to the dramatic reduction in NO production, resulting from downregulation of nitric oxide synthase (iNOS) enzyme expression.

In light of recent climate change, with its rising temperatures and precipitation changes, we are facing the need to increase the valuable crop’s tolerance against unfavorable environmental conditions. Emmer wheat is a cereal crop with high nutritional value. We investigated the possibility of improving the stress tolerance of emmer wheat by activating the synthesis of the stress hormone jasmonate by overexpressing two genes of the jasmonate biosynthetic pathway from Arabidopsis thaliana, ALLENE OXIDE SYNTHASE (AtAOS) and OXOPHYTODIENOATE REDUCTASE 3 (AtOPR3). Analyses of jasmonates in intact and mechanically wounded leaves of non-transgenic and transgenic plants showed that the overexpression of each of the two genes resulted in increased wounding-induced levels of jasmonic acid and jasmonate-isoleucine. Against all expectations, the overexpression of AtAOS, encoding a chloroplast-localized enzyme, does not lead to an increased level of the chloroplast-formed 12-oxo-phytodienoic acid (OPDA), suggesting an effective conversion of OPDA to downstream products in wounded emmer wheat leaves. Transgenic plants overexpressing AtAOS or AtOPR3 with increased jasmonate levels show a similar phenotype, manifested by shortening of the first and second leaves and elongation of the fourth leaf, as well as increased tolerance to osmotic stress induced by the presence of the polyethylene glycol (PEG) 6000.

The molecule (2S)-naringenin is a scaffold molecule with several nutraceutical properties. Currently, (2S)-naringenin is obtained through chemical synthesis and plant isolation. However, these methods have several drawbacks. Thus, heterologous biosynthesis has emerged as a viable alternative to its production. Recently, (2S)-naringenin production studies in Escherichia coli have used different tools to increase its yield up to 588 mg/L. In this study, we designed and assembled a bio-factory for (2S)-naringenin production. Firstly, we used several parametrized algorithms to identify the shortest pathway for producing (2S)-naringenin in E. coli, selecting the genes phenylalanine ammonia lipase (pal), 4-coumarate: CoA ligase (4cl), chalcone synthase (chs), and chalcone isomerase (chi) for the biosynthetic pathway. Then, we evaluated the effect of oxygen transfer on the production of (2S)-naringenin at flask (50 mL) and bench (4 L culture) scales. At the flask scale, the agitation rate varied between 50 rpm and 250 rpm. At the bench scale, the dissolved oxygen was kept constant at 5% DO (dissolved oxygen) and 40% DO, obtaining the highest (2S)-naringenin titer (3.11 ± 0.14 g/L). Using genome-scale modeling, gene expression analysis (RT-qPCR) of oxygen-sensitive genes was obtained.

’Candidatus Phytoplasma mali’, is a bacterial pathogen associated with the so-called apple proliferation disease in Malus × domestica. The pathogen manipulates its host with a set of effector proteins, among them SAP11CaPm, which shares similarity to SAP11AYWB from ’Candidatus Phytoplasma asteris’. SAP11AYWB interacts and destabilizes the class II CIN transcription factors of Arabidopsis thaliana, namely AtTCP4 and AtTCP13 as well as the class II CYC/TB1 transcription factor AtTCP18, also known as BRANCHED1 being an important factor for shoot branching. It has been shown that SAP11CaPm interacts with the Malus × domestica orthologues of AtTCP4 (MdTCP25) and AtTCP13 (MdTCP24), but an interaction with MdTCP16, the orthologue of AtTCP18, has never been proven. The aim of this study was to investigate this potential interaction and close a knowledge gap regarding the function of SAP11CaPm. A Yeast two-hybrid test and Bimolecular Fluorescence Complementation in planta revealed that SAP11CaPm interacts with MdTCP16. MdTCP16 is known to play a role in the control of the seasonal growth of perennial plants and an increase of MdTCP16 gene expression has been detected in apple leaves in autumn. In addition to this, MdTCP16 is highly expressed during phytoplasma infection. Binding of MdTCP16 by SAP11CaPm might lead to the induction of shoot proliferation and early bud break, both of which are characteristic symptoms of apple proliferation disease.

Meroterpenoids are secondary metabolites formed due to mixed biosynthetic pathways which are produced in part from a terpenoid co-substrate. These mixed biosynthetically hybrid compounds are widely produced by bacteria, algae, plants, and animals. Notably amazing chemical diversity is generated among meroterpenoids via a combination of terpenoid scaffolds with polyketides, alkaloids, phenols, and amino acids. This review deals with the isolation, chemical diversity, and biological effects of 452 new meroterpenoids reported from natural sources from January 2016 to December 2020. Most of the meroterpenoids possess antimicrobial, cytotoxic, antioxidant, anti-inflammatory, antiviral, enzyme inhibitory, and immunosupressive effects.

Ozoroa insignis Del. is an ethnobotanical plant widely used in traditional medicine for various ailments, including schistosomiasis, tapeworm, and hookworm infections. From the so far not investigated fruits of Ozoroa insignis, the anthelmintic principles could be isolated through bioassay-guided isolation using Caenorhabditis elegans and identified by NMR spectroscopic analysis and mass spectrometric studies. Isolated 6-[8(Z)-pentadecenyl] anacardic (1), 6-[10(Z)-heptadecenyl] anacardic acid (2), and 3-[7(Z)-pentadecenyl] phenol (3) were evaluated against the 5 parasitic organisms Schistosoma mansoni (adult and newly transformed schistosomula), Strongyloides ratti, Heligmosomoides polygyrus, Necator americanus, and Ancylostoma ceylanicum, which mainly infect humans and other mammals. Compounds 1–3 showed good activity against Schistosoma mansoni, with compound 1 showing the best activity against newly transformed schistosomula with 50% activity at 1µM. The isolated compounds were also evaluated for their cytotoxic properties against PC-3 (human prostate adenocarcinoma) and HT-29 (human colorectal adenocarcinoma) cell lines, whereby compounds 2 and 3 showed antiproliferative activity in both cancer cell lines, while compound 1 exhibited antiproliferative activity only on PC-3 cells. With an IC50 value of 43.2 µM, compound 3 was found to be the most active of the 3 investigated compounds.

Ranunculus muricatus L. is a spiny fruit buttercup that is used in various traditional medicinal systems. In the current investigation of R. muricatus, the new chalcone 4-benzyloxylonchocarpin (1), the new anthraquinone muracatanes A (2), the new-to-nature anthraquinone muracatanes B (3), and the new naphthalene analog muracatanes C (4) were isolated, in addition to the three previously reported compounds, 4-methoxylonchocarpin (5), β-sitosterol (6), and β-sitosterol β-D-glucopyranoside (7). Their structures were elucidated using 1D (1H and 13C) and 2D (COSY, HSQC, and HMBC) NMR spectroscopy and HR-ESI-MS. Chalcone 1 showed potent acetylcholinesterase inhibitory effects with Ki of 5.39 µM and Ki′ of 3.54 µM, but none of the isolated compounds showed inhibitory activity towards butyrylcholinesterase. Anthraquinone 3 illustrated α-glucosidase inhibitory effects with IC50-values of 164.46 ± 83.04 µM. Compound 5 displayed moderate cytotoxic activity towards ovarian carcinoma (A2780, IC50 = 25.4 µM), colorectal adenocarcinoma (HT29, IC50 = 20.2 µM), breast cancer (MCF7, IC50 = 23.7 µM), and thyroid carcinoma (SW1736, IC50 = 26.2 µM) while it was inactive towards pharynx carcinoma (FaDu: IC50 > 30 µM).

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Atypical myopathy (AM) in horses is caused by ingestion of seeds of the Acer species (Sapindaceae family). Methylenecyclopropylacetyl-CoA (MCPA-CoA), derived from hypoglycin A (HGA), is currently the only active toxin in Acer pseudoplatanus or Acer negundo seeds related to AM outbreaks. However, seeds or arils of various Sapindaceae (e.g., ackee, lychee, mamoncillo, longan fruit) also contain methylenecyclopropylglycine (MCPG), which is a structural analogue of HGA that can cause hypoglycaemic encephalopathy in humans. The active poison formed from MCPG is methylenecyclopropylformyl-CoA (MCPF-CoA). MCPF-CoA and MCPA-CoA strongly inhibit enzymes that participate in β-oxidation and energy production from fat. The aim of our study was to investigate if MCPG is involved in Acer seed poisoning in horses. MCPG, as well as glycine and carnitine conjugates (MCPF-glycine, MCPF-carnitine), were quantified using high-performance liquid chromatography-tandem mass spectrometry of serum and urine from horses that had ingested Acer pseudoplatanus seeds and developed typical AM symptoms. The results were compared to those of healthy control horses. For comparison, HGA and its glycine and carnitine derivatives were also measured. Additionally, to assess the degree of enzyme inhibition of β-oxidation, several acyl glycines and acyl carnitines were included in the analysis. In addition to HGA and the specific toxic metabolites (MCPA-carnitine and MCPA-glycine), MCPG, MCPF-glycine and MCPF-carnitine were detected in the serum and urine of affected horses. Strong inhibition of β-oxidation was demonstrated by elevated concentrations of all acyl glycines and carnitines, but the highest correlations were observed between MCPF-carnitine and isobutyryl-carnitine (r = 0.93) as well as between MCPA- (and MCPF-) glycine and valeryl-glycine with r = 0.96 (and r = 0.87). As shown here, for biochemical analysis of atypical myopathy of horses, it is necessary to take MCPG and the corresponding metabolites into consideration.

Primary and secondary metabolites exuded by plant roots have mainly been studied under laboratory conditions, while knowledge of root exudate patterns of plants growing in natural communities is very limited. Focusing on ten common European grassland plant species, we asked to which degree exuded metabolite compositions are specific to species or growth forms (forbs and grasses), depend on environments and local neighbourhoods, and reflect traditional plant functional traits. Root exudates were collected under field conditions and analysed using a non-targeted gas chromatography coupled mass spectrometry (GC-MS) approach. In total, we annotated 153 compounds of which 36 were identified by structure and name as metabolites mainly derived from the primary metabolism. Here we show by using variance partitioning, that the composition of exuded polar metabolites was mostly explained by plot identity, followed by plant species identity while plant species composition of the local neighbourhood played no role. Total and root dry biomass explained the largest proportion of variance in exudate composition, with additional variance explained by traditional plant traits. Although the exudate composition was quite similar between the two growth forms, we found some metabolites that occurred only in one of the two growth forms. Our study demonstrated the feasibility of measuring polar exudates under non-sterile field conditions by mass spectrometry, which opens new avenues of research for functional plant ecology.