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Topics in Current Chemistry (Cham) Sep 2023BODIPY (4-bora-3a,4a-diaza-s-indacene) dyes are regarded as highly useful compounds due to their rich photophysical properties, stability, and ease of functionalization.... (Review)
Review
BODIPY (4-bora-3a,4a-diaza-s-indacene) dyes are regarded as highly useful compounds due to their rich photophysical properties, stability, and ease of functionalization. In recent years, hot topics studied with this class of compounds are targeted photodynamic therapy, photothermal therapy, fluorescent bioimaging agents, structural modification of the BODIPY core, synthesis of BODIPY analogs, and BODIPY-based supramolecular constructs. This review covers the advances in BODIPY structures substituted with additional carbon-nitrogen double bonds, namely imines, hydrazones, oximes, and related derivatives for various applications. Works based on fluorescent indicators of anions, cations, and neutral molecules are included in this review. In addition, the use of such structures for pharmaceutical applications, photodynamic therapy, fluorescent switches, and fluorescent building blocks are also investigated. In addition to covering the major literature within the mentioned subclass, design principles, working mechanisms, and outlooks are also provided to enlighten forthcoming promising efforts. With this work, we aim to provide insights about the synthesis, photophysical properties, contribution of C=N bonds to a class of dye, and possible areas of use and stimulate researchers to present new ideas and overcome the current problems using these derivatives.
Topics: Fluorescent Dyes; Carbon; Hydrazones; Imines
PubMed: 37676540
DOI: 10.1007/s41061-023-00438-5 -
Frontiers in Veterinary Science 2023Milbemycin oxime (MBO) and praziquantel (PZQ) have a broad spectrum of biological activity and are commonly used to treat the parasitic infection in the veterinary...
Development and validation of an LC-MS/MS method for the simultaneous quantification of milbemycin oxime and praziquantel in plasma: application to a pharmacokinetic study in cats.
INTRODUCTION
Milbemycin oxime (MBO) and praziquantel (PZQ) have a broad spectrum of biological activity and are commonly used to treat the parasitic infection in the veterinary clinic. In this study, a fast and efficient LC-MS/MS method was established and validated for the simultaneous determination of MBO, PZQ, cis-4-hydroxylated-PZQ (C-4-OH-PZQ) and trans-4-hydroxylated-PZQ (T-4-OH-PZQ) and in cat plasma.
METHODS
Extraction of analytes and internal standards from cat plasma by acetonitrile protein precipitation, allows rapid processing of large batches of samples. MBO, PZQ, C-4-OH-PZQ, T-4-OH-PZQ, and internal standard (IS) were eluted for 13.5 min on a C column with a 0.1% formic acid water/acetonitrile mixture as the mobile phase.
RESULTS
Results showed that the method had good precision, accuracy, recovery, and linearity. The linearity range was 2.5-250 ng/mL for MBO, and 10-1000 ng/mL for PZQ, C-4-OH-PZQ, and T-4-OH-PZQ. The intra-day and inter-day precision CV values of the tested components were within 15%. The extraction recoveries of the four components ranged from 98.09% to 107.46%. The analytes in plasma remained stable for 6 h at room temperature, 26 h in the autosampler (4 °C), after freeze-thaw (-20°C) cycles, and 60 days in a -20°C freezer. Method sensitivity sufficed for assessing pharmacokinetic parameters of MBO, PZQ, C-4-OH-PZQ, and T-4-OH-PZQ in plasma samples with LLOQ of 2.5 ng/mL for MBO and 10 ng/mL for PZQ, C-4-OH-PZQ, and T-4-OH-PZQ.
CONCLUSION
In this study, a selective and sensitive LC-MS/MS method for the simultaneous quantification of MBO, PZQ, C-4-OH-PZQ, and T-4-OH-PZQ in cat plasma was developed and validated.This method had been successfully applied to evaluate the pharmacokinetics of MBO, PZQ, C-4-OH-PZQ, and T-4-OH-PZQ after a single oral administration of 8 mg MBO and 20 mg PZQ in cats.
PubMed: 37964913
DOI: 10.3389/fvets.2023.1285932 -
Pest Management Science Aug 2023Vegetable viruses are difficult to prevent and control in the field, causing massive economic losses of agricultural production in the world. A new natural product-based...
BACKGROUND
Vegetable viruses are difficult to prevent and control in the field, causing massive economic losses of agricultural production in the world. A new natural product-based antiviral agent would be an effective means to control viral diseases. As a class of natural products, 1-indanones present various pharmacologically actives, while their application in agriculture remains to be found.
RESULTS
A series of novel 1-indanone derivatives were designed and synthesized and the antiviral activities were systematically evaluated. Bioassays showed that most compounds exhibited good protective activities against cucumber mosaic virus (CMV), tomato spotted wilt virus (TSWV), and pepper mild mottle virus (PMMoV). Notably, compound 27 exhibited the best protective effects against PMMoV with EC values of 140.5 mg L , superior to ninanmycin (245.6 mg L ). Compound 27 induced immunity responses through multilayered regulation on mitogen-activated protein kinase, plant hormone signal transduction and phenylpropanoid biosynthesis pathways.
CONCLUSION
These 1-indanone derivatives especially compound 27 can be considered as potential immune activators to resist plant virus. © 2023 Society of Chemical Industry.
Topics: Ether; Plant Viruses; Indans; Ethers; Ethyl Ethers; Antiviral Agents
PubMed: 36883547
DOI: 10.1002/ps.7442 -
European Journal of Pharmaceutical... Mar 2024Parkinson's disease is the second most prevalent age-related neurodegenerative disease and disrupts the lives of people aged >60 years. Meanwhile, single-target drugs...
Parkinson's disease is the second most prevalent age-related neurodegenerative disease and disrupts the lives of people aged >60 years. Meanwhile, single-target drugs becoming inapplicable as PD pathogenesis diversifies. Mitochondrial dysfunction and neurotoxicity have been shown to be relevant to the pathogenesis of PD. The novel synthetic compound J24335 (11-Hydroxy-1-(8-methoxy-5-(trifluoromethyl)quinolin-2-yl)undecan-1-one oxime), which has been researched similarly to J2326, has the potential to be a multi-targeted drug and alleviate these lesions. Therefore, we investigated the mechanism of action and potential neuroprotective function of J24335 against 6-OHDA-induced neurotoxicity in mice, and in PC12 cell models. The key target of action of J24335 was also screened. MTT assay, LDH assay, flow cytometry, RT-PCR, LC-MS, OCR and ECAR detection, and Western Blot analysis were performed to characterize the neuroprotective effects of J24335 on PC12 cells and its potential mechanism. Behavioral tests and immunohistochemistry were used to evaluate behavioral changes and brain lesions in mice. Moreover, bioinformatics was employed to assess the drug-likeness of J24335 and screen its potential targets. J24335 attenuated the degradation of mitochondrial membrane potential and enhanced glucose metabolism and mitochondrial biosynthesis to ameliorate 6-OHDA-induced mitochondrial dysfunction. Animal behavioral tests demonstrated that J24335 markedly improved motor function and loss of TH-positive neurons and dopaminergic nerve fibers, and contributed to an increase in the levels of dopamine and its metabolites in brain tissue. The activation of both the CREB/PGC-1α/NRF-1/TFAM and PKA/Akt/GSK-3β pathways was a major contributor to the neuroprotective effects of J24335. Furthermore, bioinformatics predictions revealed that J24335 is a low toxicity and highly BBB permeable compound targeting 8 key genes (SRC, EGFR, ERBB2, SYK, MAPK14, LYN, NTRK1 and PTPN1). Molecular docking suggested a strong and stable binding between J24335 and the 8 core targets. Taken together, our results indicated that J24335, as a multi-targeted neuroprotective agent with promising therapeutic potential for PD, could protect against 6-OHDA-induced neurotoxicity via two potential pathways in mice and PC12 cells.
Topics: Humans; Rats; Mice; Animals; Oxidopamine; Neuroprotective Agents; PC12 Cells; Neurodegenerative Diseases; Glycogen Synthase Kinase 3 beta; Molecular Docking Simulation; Dopamine; Mitochondrial Diseases; Dopaminergic Neurons
PubMed: 38199443
DOI: 10.1016/j.ejps.2024.106696 -
Organic Letters Sep 2023In this study, we developed a strategy using commercially available alkyl iodides and -benzoyl oxime to efficiently introduce alkyl and iminyl groups via energy transfer...
In this study, we developed a strategy using commercially available alkyl iodides and -benzoyl oxime to efficiently introduce alkyl and iminyl groups via energy transfer and halogen-atom transfer processes. We performed three-component 1,2-carboimination of olefins and four-component 1,4-carboimination across olefins and alkynes, resulting in the synthesis of over 60 nitrogen-containing molecules. Moreover, this transformation enables the synthesis of molecules with sensitive groups that were previously difficult to achieve.
PubMed: 37607051
DOI: 10.1021/acs.orglett.3c02440 -
Reviews in Medical Virology Jan 2024This systematic review and meta-analysis of randomised controlled trials (RCTs) aimed to evaluate the efficacy, safety, and tolerability of fluvoxamine for the... (Meta-Analysis)
Meta-Analysis Review
This systematic review and meta-analysis of randomised controlled trials (RCTs) aimed to evaluate the efficacy, safety, and tolerability of fluvoxamine for the outpatient management of COVID-19. We conducted this review in accordance with the PRISMA 2020 guidelines. Literature searches were conducted in MEDLINE, EMBASE, International Pharmaceutical Abstracts, CINAHL, Web of Science, and CENTRAL up to 14 September 2023. Outcomes included incidence of hospitalisation, healthcare utilization (emergency room visits and/or hospitalisation), mortality, supplemental oxygen and mechanical ventilation requirements, serious adverse events (SAEs) and non-adherence. Fluvoxamine 100 mg twice a day was associated with reductions in the risk of hospitalisation (risk ratio [RR] 0.75, 95% confidence interval [CI] 0.58-0.97; I = 0%) and reductions in the risk of healthcare utilization (RR 0.68, 95% CI 0.53-0.86; I = 0%). While no increased SAEs were observed, fluvoxamine 100 mg twice a day was associated with higher treatment non-adherence compared to placebo (RR 1.61, 95% CI 1.22-2.14; I = 53%). In subgroup analyses, fluvoxamine reduced healthcare utilization in outpatients with BMI ≥30 kg/m , but not in those with lower BMIs. While fluvoxamine offers potential benefits in reducing healthcare utilization, its efficacy may be most pronounced in high-risk patient populations. The observed non-adherence rates highlight the need for better patient education and counselling. Future investigations should reassess trial endpoints to include outcomes relating to post-COVID sequelaes. Registration: This review was prospectively registered on PROSPERO (CRD42023463829).
Topics: Humans; COVID-19; Outpatients; Fluvoxamine; COVID-19 Drug Treatment
PubMed: 38148036
DOI: 10.1002/rmv.2501 -
Reviews in Medical Virology Jul 2024
Topics: Humans; COVID-19 Drug Treatment; Fluvoxamine; COVID-19; SARS-CoV-2; Post-Acute COVID-19 Syndrome; Selective Serotonin Reuptake Inhibitors
PubMed: 38825753
DOI: 10.1002/rmv.2557 -
Malaria Journal Aug 2023The objective of this study was to determine the susceptibility of wild Anopheles gambiae sensu lato (s.l.) from southern Benin to the new insecticides (chlorfenapyr...
Assessing the susceptibility and efficacy of traditional neurotoxic (pyrethroid) and new-generation insecticides (chlorfenapyr, clothianidin, and pyriproxyfen), on wild pyrethroid-resistant populations of Anopheles gambiae from southern Benin.
BACKGROUND
The objective of this study was to determine the susceptibility of wild Anopheles gambiae sensu lato (s.l.) from southern Benin to the new insecticides (chlorfenapyr (CFP), pyriproxyfen (PPF), and clothianidin (CTD)) and assess the efficacy of insecticide-treated bed nets (ITNs) that contain these new products.
METHODS
Wild An. gambiae from the Benin communes of Allada, Ifangni, Akpro-Missérété, and Porto-Novo were tested for their susceptibility to CFP and PPF using the WHO bottle tests, and pyrethroids (alpha-cypermethrin, deltamethrin, and permethrin) and CTD using WHO tube tests. WHO cone tests were used to evaluate the efficacy of Interceptor (which contains alpha-cypermethrin (ACM) only), Interceptor G2, (CFP + ACM), and Royal Guard nets (PPF + ACM). The ovaries of blood-fed An. gambiae from Ifangni exposed to a new PPF net were dissected, and egg development status was examined using Christopher's stages to determine the fertility status of the mosquitoes. Using a standardized protocol, the oviposition rate and oviposition inhibition rate were calculated from live blood-fed An. gambiae placed in oviposition chambers after exposure to PPF.
RESULTS
In all four mosquito populations, pyrethroid mortality ranged from 5 to 80%, while chlorfenapyr and clothianidin mortality ranged from 98 to 100%. At Ifangni, all mosquitoes exposed to Royal Guard® nets were infertile (100%) while the majority (74.9%) of mosquitoes exposed to Interceptor® nets had fully developed their eggs to Christopher's stage V. The oviposition inhibition rate after exposure of the mosquitoes to the PPF was 99% for the wild population of An. gambiae s.l. and the susceptible laboratory strain, An. gambiae sensu stricto (Kisumu).
CONCLUSIONS
The results of this study suggest that pyrethroid-resistant An. gambiae from the selected communes in southern Benin are susceptible to chlorfenapyr, clothianidin, and pyriproxyfen. In addition, based on bioassay results, new and unused Interceptor® G2 and Royal Guard® nets were effective on Ifangni's mosquito populations. Despite the availability of new effective insecticides, continued vigilance is needed in Benin. Therefore, monitoring of resistance to these insecticides will continue to periodically update the Benin national insecticide resistance database and management plan.
Topics: Animals; Female; Insecticides; Anopheles; Benin; Permethrin
PubMed: 37626366
DOI: 10.1186/s12936-023-04664-6 -
Polymers Dec 2023Several cobalt(II) complexes - bearing pyridine-oxime ligands ( = pyridine-2-aldoxime for ; = 6-methylpyridine-2-aldoxime for ; = phenyl-2-pyridylketoxime for ) and...
Several cobalt(II) complexes - bearing pyridine-oxime ligands ( = pyridine-2-aldoxime for ; = 6-methylpyridine-2-aldoxime for ; = phenyl-2-pyridylketoxime for ) and picolinaldehyde O-methyl oxime ()-supported were synthesized and well characterized by FT-IR, mass spectrum and elemental analysis. The single-crystal X-ray diffraction of complex reveals that the cobalt center of CoCl is coordinated with two 6-methylpyridine-2-aldoxime ligands binding with and atoms, which feature a distorted octahedral structure. These Co complexes - displayed extremely high activity toward isoprene polymerization upon activation with small amount of AlClEt in toluene, giving polyisoprene with high activity up to 16.3 × 10 (mol of Co)(h). And, the generated polyisoprene displayed high molecular weights and narrow molecular distribution with a -1,4-enriched selectivity. The type of cobalt complexes, cocatalyst and reaction temperature all have effects on the polymerization activity but not on the microstructure of polymer.
PubMed: 38139912
DOI: 10.3390/polym15244660 -
Neurology May 2024Clinical heterogeneity of patients with Parkinson disease (PD) is well recognized. PD with REM sleep behavior disorder (RBD) is a more malignant phenotype with faster...
BACKGROUND AND OBJECTIVES
Clinical heterogeneity of patients with Parkinson disease (PD) is well recognized. PD with REM sleep behavior disorder (RBD) is a more malignant phenotype with faster motor progression and higher nonmotor symptom burden. However, the neural mechanisms underlying this clinical divergence concerning imbalances in neurotransmitter systems remain elusive.
METHODS
Combining magnetic resonance (MR) spectroscopy and [C]ABP688 PET on a PET/MR hybrid system, we simultaneously investigated two different mechanisms of glutamate signaling in patients with PD. Patients were grouped according to their RBD status in overnight video-polysomnography and compared with age-matched and sex-matched healthy control (HC) participants. Total volumes of distribution (V) of [C]ABP688 were estimated with metabolite-corrected plasma concentrations during steady-state conditions between 45 and 60 minutes of the scan following a bolus-infusion protocol. Glutamate, glutamine, and glutathione levels were investigated with single-voxel stimulated echo acquisition mode MR spectroscopy of the left basal ganglia.
RESULTS
We measured globally elevated V of [C]ABP688 in 16 patients with PD and RBD compared with 17 patients without RBD and 15 HC participants ((2,45) = 5.579, = 0.007). Conversely, glutamatergic metabolites did not differ between groups and did not correlate with the regional V of [C]ABP688. V of [C]ABP688 correlated with the amount of REM sleep without atonia ((1,42) = 5.600, = 0.023) and with dopaminergic treatment response in patients with PD ((1,30) = 5.823, = 0.022).
DISCUSSION
Our results suggest that patients with PD and RBD exhibit altered glutamatergic signaling indicated by higher V of [C]ABP688 despite unaffected glutamate levels. The imbalance of glutamate receptors and MR spectroscopy glutamate metabolite levels indicates a novel mechanism contributing to the heterogeneity of PD and warrants further investigation of drugs targeting mGluR5.
Topics: Humans; Parkinson Disease; REM Sleep Behavior Disorder; Oximes; Glutamates; Pyridines
PubMed: 38630966
DOI: 10.1212/WNL.0000000000209271