Synthesis of novel naphthalene-chimonanthine scaffolds hybrids with potent antibacterial or antifungal activity.

In this work, a total of 19 novel naphthalene hybrids with chimonanthine scaffolds were efficiently synthesised from indole-3-acetonitrile in good yields. The prepared compounds were evaluated for biological activity against Cryptococcus neoformans, Escherichia coli, Shigella spp, Candida albicans, Salmonella spp, and Staphylococcus aureus. The preliminary bioassays showed that most of the synthesised compounds exhibited significant antibacterial or antifungal activity. Notably, compound 8 showed potent activity against Cryptococcus neofonmans, Escherichia coli, Shigella spp, and Candida albicans than the positive control, all with the same MIC value of 3.53 µM. Compound 8 had a broad spectrum of antibacterial or antifungal activity, and will be studied further.

Synthesis and antifungal activity of novel chiral indole analogues.

Starting from L-tryptophan, 19 new N-substituted chiral indole analogs were synthesized. The prepared compounds were evaluated for biological activity against Sclerotinia sclerotiorum, Alternaria solani, Verticillium dahliae, Colletotrichum orbiculare, Cytospora juglandis and Curvularia lunata. The preliminary bioassays showed that most of the synthesized compounds exhibited fungicidal activity. Compound b13 in particular exhibited significant antifungal activity against Verticillium dahliae and Sclerotinia sclerotiorum, with the MIC value of 1.95 µg mL-1. Compound b13 also showed excellent activity against six plant pathogen fungi, and was identified as the most active on the biological assays, and will be studied further.

Sevoflurane Ameliorates Schizophrenia in a Mouse Model and Patients: A Pre-Clinical and Clinical Feasibility Study.

BACKGROUND: GABAergic deficits have been considered to be associated with the pathophysiology of schizophrenia, and hence, GABA receptors subtype A (GABAARs) modulators, such as commonly used volatile anesthetic sevoflurane, may have therapeutic values for schizophrenia. The present study investigates the therapeutic effectiveness of low-concentration sevoflurane in MK801-induced schizophrenia-like mice and schizophrenia patients. METHODS: Three weeks after MK801 administration (0.5 mg kg-1, i.p. twice a day for 5 days), mice were exposed to 1% sevoflurane 1hr/day for 5 days. Behavioral tests, immunohistochemical analysis, western blot assay, and electrophysiology assessments were performed 1-week post-exposure. Ten schizophrenia patients received 1% sevoflurane 5 hrs per day for 6 days and were assessed with the Positive and Negative Syndrome Scale (PANSS) and the 18-item Brief Psychiatric Rating Scale (BPRS-18) at week 1 and week 2. RESULTS: MK801 induced hypolocomotion and social deficits, downregulated expression of NMDARs subunits and postsynaptic density protein 95 (PSD95), reduced parvalbumin - and GAD67-positive neurons, altered amplitude and frequency of mEPSCs and mIPSCs, and increased the excitation/inhibition ratio. All these changes induced by MK-801 were attenuated by sevoflurane administration. Six and eight patients achieved a response defined as a reduction of at least 30% in the PANSS total score at 1st and 2nd week after treatments. The BPRS-18 total score was found to be significantly decreased by 38% at the 2nd week (p < 0.01). CONCLUSION: Low-concentration sevoflurane effectively reversed MK801-induced schizophrenialike disease in mice and alleviated schizophrenia patients' symptoms. Our work suggests sevoflurane to be a valuable therapeutic strategy for treating schizophrenia patients.