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[Display omitted] Five-membered heterocycles containing nitrogen, oxygen atoms, especially isoxazoles, are widely present in many natural products and drugs and have relevant medical and pharmaceutical applications. Due to their rich biological activity, the development of novel isoxazole derivatives has been the focus of researchers and scientists. It is worth noting that a large number of isoxazoles have been used frequently as clinical drugs to treat various diseases, showing great development value and wide medicinal potential. In this review, the research progress of isoxazole natural products in anti-bacterial, anti-tuberculosis, anti-virus, anti-tumor, anti-inflammation, anti-diabetes, anti-parasite, anti-psychosis and other biological activities was reviewed. Finally, the research and development prospects of isoxazole natural products were prospected. This review will provide reference for the design of natural isoxazole products with stronger activity and less toxicity. [ABSTRACT FROM AUTHOR]

In this study, a novel series of isoxazole-naphthalene derivatives as tubulin polymerization inhibitors were designed, synthesized and evaluated for their anti-proliferative activities against human breast cancer cell line MCF-7. Most of the synthesized compounds exhibited moderate to potent antiproliferative activity (IC 50 < 10.0 μM), as compared to cisplatin (15.24 ± 1.27 μM). Among them, compound 5j containing 4-ethoxy substitution at phenyl ring was found to be the most active compound with IC 50 value of 1.23 ± 0.16 μM. Mechanistic studies revealed that compound 5j arrested cell cycle at G2/M phase and induces apoptosis. Furthermore, in vitro tubulin polymerization assay showed that compound 5j displayed better inhibition activity on tubulin polymerization (IC 50 = 3.4 μM) than colchicine (IC 50 = 7.5 μM). Molecular docking study also revealed that compound 5j binds to the colchicine binding site of tubulin. [ABSTRACT FROM AUTHOR]

Enteroendocrine cells (EECs) survey the gut luminal environment and coordinate hormonal, immune and neuronal responses to it. They exhibit well-characterised physiological roles ranging from the control of local gut function to whole body metabolism, but little is known regarding the regulatory networks controlling their differentiation, especially in the human gut. The small molecule isoxazole-9 (ISX-9) has been shown to stimulate neuronal and pancreatic beta-cell differentiation, both closely related to EEC differentiation. Our aim was to use ISX-9 as a tool to explore EEC differentiation. We investigated the effects of ISX-9 on EEC differentiation in mouse and human intestinal organoids, using real-time quantitative polymerase chain reaction (RT-qPCR), fluorescent-activated cell sorting, immunostaining and single-cell RNA sequencing. ISX-9 increased the number of neurogenin3-RFP (Ngn3)-positive endocrine progenitor cells and upregulated NeuroD1 and Pax4, transcription factors that play roles in mouse EEC specification. Single-cell analysis showed induction of Pax4 expression in a developmentally late Ngn3+ population of cells and potentiation of genes associated with progenitors biased toward serotonin-producing enterochromaffin (EC) cells. Further, we observed enrichment of organoids with functional EC cells that was partly dependent on stimulation of calcium signalling in a population of cells residing outside the crypt base. Inducible Pax4 overexpression, in ileal organoids, uncovered its importance as a component of early human endocrine specification and highlighted the potential existence of two major endocrine lineages, the early appearing enterochromaffin lineage and the later developing peptidergic lineage which contains classical gut hormone cell types. Our data provide proof-of-concept for the controlled manipulation of specific endocrine lineages with small molecules, whilst also shedding new light on human EEC differentiation and its similarity to the mouse. Given their diverse roles, understanding endocrine lineage plasticity and its control could have multiple therapeutic implications. Image 1 • ISX-9 promotes flux through the Ngn3 lineage and enriches it with enterochromaffin cells. • ISX-9 engages an enterochromaffin biased transcriptional programme in endocrine fated cells. • Enterochromaffin bias is partly dependent on calcium signalling in progenitor cells. • ISX-9 reveals conserved gut endocrine specification between mouse and human. • Pax4 overexpression in human ileum organoids mimics the effects of ISX-9 on EC bias. [ABSTRACT FROM AUTHOR]

[Display omitted] • 3,5-disubstituted isoxazole exhibits excellent antitrypanosomal activity compared to drug reference, pentamidine. • Molecular docking shows seven hydrogen interactions and low binding energy for 3,5-disubstituted isoxazole. • 3,5-disubstituted isoxazole shows considerable stability during MD simulation compared to drug reference, pentamidine. • Quantum Theory of Atoms in Molecules (AIM) and Non-Covalent Interaction (NCI) analysis corroborate molecular docking and MD simulation findings revealing the strength of H-bonds found. • Cycloaddition [3 + 2] follows reverse electron demand, and dechloromethane has a significant impact on the regioselectivity. The antitrypanosomal activity of 3,5-disubstituted isoxazole has been investigated through molecular docking, revealing its binding to Plasmodium falciparum through seven hydrogen interactions demonstrating high affinity, supported by Molecular Dynamics Simulations. Followed by the Quantum Theory of Atoms in Molecules (AIM) studies, confirming the strength of hydrogen bonds and an acceptable ADMET profile has been found. The chemical reactivity of the cycloaddition [3 + 2] has been explored using Density Functional Theory (DFT). Results revealed a reverse electron demand, which was confirmed by global reactivity indices. Electron displacement was investigated based on Fukui functions, Methyl Cation Affinity (MCA), Methyl Anion Affinity (MAA), and Molecular Electrostatic Potential (MEP). The regioselectivity of the reaction was explored in the gas phase first and in dichloromethane secondarily to assess their impact on the reaction using the Integral Equation Formalism Polarizable Continuum (IEFPCM) model. Finally, additional bioactive compounds with 3,5-disubstituted isoxazole properties have been found using screening methods. [ABSTRACT FROM AUTHOR]

A new series of pyrazole, isoxazole, benzoxazepine, benzothiazepine and benzodiazepine derivatives were prepared by the multi-component cyclo-condensation reaction of 1-phenyl-3-(2-(tosyloxy)phenyl)propane-1,3-dione, N , N -dimethylformamide dimethyl acetal and hydrazine or hydroxylamine hydrochloride or 2-aminothiophenol or 2-aminophenol or benzene-1,2-diamine using μwave technique in aqueous media. All the synthesized compounds were evaluated for their anti-bacterial and antifungal activities. Some of the selected compounds were also screened for their anti-inflammatory activity. [ABSTRACT FROM AUTHOR]

A new regioselective method for the synthesis of 2-aryl-5-benzoylpyridine derivatives has been developed. The reaction proceeds via ring opening and closing cascade mechanism (ROCC) of isoxazole to synthesize various functionalized pyridine derivatives. This is the first report for the preparation of 2,5-di-substituted pyridines using Fe/NH 4 Cl as a reducing reagent. [ABSTRACT FROM AUTHOR]

Because of the highly therapeutic nature of 1,2,4-triazoles, a new class of fused pyrazolo [3′,4′:4,5] thiazolo [3,2-b] [1,2,4]-triazole, isoxazolo [3′,4′:4,5] thiazolo [3,2-b] [1,2,4]-triazole moieties were prepared from the novel conventional methods via the reaction of 4-methyl benzoyl thiosemicarbazide with the appropriate chemical reagents. These compounds were screened for their antimicrobial activity against various bacterial and fungal strains. With the reference of antimicrobial activity data the synthesized compounds were further screened for their antimycobacterial activity against Mycobacterium tuberculosis H 37 Rv by the conventional methods. Among the synthesized compounds 4b, 4d, 4h, 5d and 5h have shown more activity compared to the standard drugs. [ABSTRACT FROM AUTHOR]

A variety of novel isatin derivatives 5a-5j and 6a-6j were synthesized and characterized by spectroscopic means and elemental analysis. The title compounds were investigated for antiepileptic activity using MES and scPTZ seizures tests. Neurotoxicity study was performed by the rotorod test. The relationship between the functional group variation and the biological activity of the evaluated compounds was discussed. Among the synthesized analogs, the most active one was 6f that revealed protection in MES at a dose of 30mg/kg (i.p.) after 0.5h and 4h. This molecule also provided protection in the scPTZ at a dose of 100mg/kg (0.5h) and 300mg/kg (4h). [ABSTRACT FROM AUTHOR]

Abstract: Triphenylphosphine and dialkyl acethylenedicarboxylates in the presence of 3,4-dihydro-3-hydroxy-4-oxo-1,2,3-benzotriazine react in one-pot to afford novel highly functionalized Isoxazoles in fairly good yields at room temperature. When 3,4-dihydro-3-hydroxy-4-oxo-1,2,3-triazine were employed in these reactions, related isoxazole rings were obtained in good yields. [Copyright &y& Elsevier]