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As part of our search for bioactive compounds from plant biodiversity, 29 withanolides were recently isolated from three members of the Solanaceae: Physalis longifolia, Vassobia breviflora, and Withania somnifera. Six derivatives were prepared from these naturally occurring withanolides. All compounds were evaluated for in vitro antiproliferative activity against an array of cell lines [melanoma cell lines (B16F10, SKMEL28); human head and neck squamous cell carcinomas (HNSCC) cell lines (JMAR, MDA1986, DR081-1); breast cancer cell line (Hs578T), and non-malignant human cell line (MRC5)]. This led to the discovery of 15 withanolides, with IC 50 values in the range of 0.067−17.4 μM, including withaferin A, withaferin A 4,27-diacetate, 27-O-glucopyranosylwithaferin A, withalongolide H, withalongolide C, withalongolide A, withalongolide A 4,27-diacetate, withalongolide A 4,19,27-triacetate, withalongolide B, withalongolide B 4-acetate, withalongolide B 4,19-diacetate, withalongolide D, withalongolide E, withalongolide G, and 2,3-dihydrowithaferin A 3-O-sulfate. In order to update the growing literature on withanolides and their activities, we summarized the distribution, structural types, and antiproliferative activities for all published withanolides to date. The structure-activity relationship analysis (SARA) confirmed the importance of the presence of a Δ 2 -1-oxo-functionality in ring A, a 5β,6β-epoxy or 5α-chloro-6β-hydroxy grouping in ring B, and nine-carbon side chain with a lactone moiety for cytotoxic activity. Conversely, the SARA indicated that the -OH or -OR groups at C-4, 7, 11, 12, 14, 15, 16, 17, 18, 19, 20, 23, 24, 27, and 28 were not contributors to the observed antiproliferative activity within the systems analyzed.

Acarbose is a bacterial-derived α-glucosidase inhibitor clinically used to treat patients with type 2 diabetes. As type 2 diabetes is on the rise worldwide, the market demand for acarbose has also increased. Despite its significant therapeutic importance, how it is made in nature is not completely understood. Here, we report the complete biosynthetic pathway to acarbose and its structural components, GDP-valienol and O-4-amino-(4,6-dideoxy-α-D-glucopyranosyl)-(1→4)-O-α-D-glucopyranosyl-(1→4)-D-glucopyranose. GDP-valienol is derived from valienol 7-phosphate, catalyzed by three cyclitol modifying enzymes, whereas O-4-amino-(4,6-dideoxy-α-D-glucopyranosyl)-(1→4)-O-α-D-glucopyranosyl-(1→4)-D-glucopyranose is produced from dTDP-4-amino-4,6-dideoxy-D-glucose and maltose by the glycosyltransferase AcbI. The final assembly process is catalyzed by a pseudoglycosyltransferase enzyme, AcbS, which is a homologue of AcbI but catalyzes the formation of a non-glycosidic C-N bond. This study clarifies all previously unknown steps in acarbose biosynthesis and establishes a complete pathway to this high value pharmaceutical.

An inadequate response from macrophages, key orchestrators of the wound healing process, has been implicated in the pathophysiology of impaired healing in diabetes. This study explored the utility of nanoparticles presenting the α‐gal (Galα1‐3Galβ1‐4GlcNAc‐R) epitope to induce anti‐Gal antibody‐mediated local transient recruitment of macrophages to accelerate wound closure and healing in a diabetic murine model. α1,3galactosyltrasferase knockout mice were stimulated to produce anti‐Gal antibodies and subsequently diabetes was induced by streptozotocin‐induced β‐cell destruction. Six mm full‐thickness skin wounds were made and α‐gal nanoparticles (AGN) were topically applied on postwounding days 0 and 1. Wounds were analysed histologically for macrophage invasion and markers of wound healing, including epithelialization, vascularization and granulation tissue deposition through postoperative day 12. We found that application of AGN transiently but significantly increased macrophage recruitment into the wounds of diabetic mice. Treated wounds demonstrated more rapid closure and enhanced wound healing as demonstrated by significantly accelerated rates of epithelialization, vascularization and granulation tissue deposition. Thus, topical treatment of full‐thickness wounds in diabetic mice with α‐gal nanoparticles induced a transient but significant increase in macrophage recruitment resulting in an accelerated rate of wound healing. Using α‐gal nanoparticles as a topical wound healing adjunct is a simple, safe and effective means of augmenting dysregulated macrophage recruitment present in the diabetic state.

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In this study, we have employed dithiooxamide, a solid, odorless, and commercially available compound, as a sulfur surrogate for the preparation of dialkyl sulfides from available alkyl halides in high yields. This sulfur transfer agent was also used for a copper‐catalyzed high‐yielding preparation of diaryl sulfides from their available aryl halides and for the preparation of thia‐Michael adducts in high yields. All the reactions were performed under odorless conditions in wet PEG200 (PEG = polyethylene glycol), which is an eco‐friendly, safe, and recoverable solvent. The protocols were easily applicable to large‐scale operation.

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A new 2-arylbenzofuran, sesbagrandiflorain C (1), together with four known compounds, 2-(3,4dihydroxy-2-methoxyphenyl)-4-hydroxy-6-methoxybenzofuran-3-carbaldehyde (2), 2-(4hydroxy-2-methoxyphenyl)-5,6-dimethoxybenzofuran-3-carboxaldehyde (3), sesbagrandiflorain A (4) and sesbagrandiflorain B (5), have been isolated from the stem bark of an Indonesian plant, Sesbania grandiflora (L.) Pers. The chemical structure of compound 1 was elucidated by UV, IR, MS, and NMR spectroscopic techniques. The proton and carbon NMR resonances of 1 were also compared with the predicted chemical shifts obtained from DFT quantum mechanical calculations with Gaussian. None of the compounds showed antibacterial activity against Bacillus subtilis, Escherichia coli, Mycobacterium smegmatis, Pseudomonas aeruginosa, and Staphylococcus aureus in an agar diffusion assay. However, sesbagrandiflorains A (4) and B (5) exhibited moderate activity against Mycobacterium tuberculosis H37Rv. In addition, compounds 1 -5 have moderate cytotoxicity against HeLa, HepG2, and MCF-7 cancer cell lines.