Ischemic stroke (IS) is a prevalent neurological disorder often resulting in significant disability or mortality. Resveratrol, extracted from Polygonum cuspidatum Sieb. et Zucc. (commonly known as Japanese knotweed), has been recognized for its potent neuroprotective properties. However, the neuroprotective efficacy of its derivative, (E)-4-(3,5-dimethoxystyryl) quinoline (RV02), against ischemic stroke remains inadequately explored. This study aimed to evaluate the protective effects of RV02 on neuronal ischemia-reperfusion injury both in vitro and in vivo. The research utilized an animal model of middle cerebral artery occlusion/reperfusion and SH-SY5Y cells subjected to oxygen-glucose deprivation and reperfusion to simulate ischemic conditions. The findings demonstrate that RV02 attenuates neuronal mitochondrial damage and scavenges reactive oxygen species (ROS) through mitophagy activation. Furthermore, Parkin knockdown was found to abolish RV02's ability to activate mitophagy and neuroprotection in vitro. These results suggest that RV02 shows promise as a neuroprotective agent, with the activation of Parkin-mediated mitophagy potentially serving as the primary mechanism underlying its neuroprotective effects.
Animals ; Ubiquitin-Protein Ligases/genetics* ; Mitophagy/drug effects* ; Resveratrol/analogs & derivatives* ; Neuroprotective Agents/pharmacology* ; Humans ; Neurons/metabolism* ; Reactive Oxygen Species/metabolism* ; Ischemic Stroke/genetics* ; Male ; Quinolines/pharmacology* ; Mice ; Fallopia japonica/chemistry* ; Mitochondria/metabolism* ; Reperfusion Injury/metabolism* ; Rats ; Mice, Inbred C57BL ; Disease Models, Animal

2-substituted quinolines are the building blocks for the synthesis of natural products and pharmaceuticals. In comparison with classical methods, dehydroaromatization of 2-substituted-1,2,3,4-tetrahydroquinolines has emerged in recent years as an efficient and straightforward method to synthesize quinolines due to its high atom economy and sustainability. However, existing chemical methods need transition metal catalysts and harsh reaction conditions. Biocatalysis with high efficiency, high selectivity, and mild reaction conditions has become an important method of organic synthesis. We mined a strain Pseudomonas monteilii ZMU-T06 capable of producing monoamine oxidase for the dehydroaromatization of 2-substituted-1,2,3,4-tetrahydroquinolines to synthesize 2-substituted quinolines (8 substrates, yields of 45.7%-48.4%) and then hypothesized the catalytic mechanism, providing a new method for green synthesis of 2-substituted quinolines.
Quinolines/chemistry* ; Pseudomonas/classification* ; Oxidation-Reduction ; Monoamine Oxidase/biosynthesis* ; Biocatalysis

The root bark of Dictamnus dasycarpus is one of common traditional Chinese medicines (TCMs). Quinoline alkaloids are one of the main active substances in this TCM and possess many biological activities including anti-titumor, anti-inflammation, anti-bacteria, anti-oxidation, and anti-platelet aggregation activities. In this study, eight quinoline alkaloids 1-8 were firstly separated from the root barks of D. dasycarpus. It was difficult to isolate more quinoline alkaloids from the remaining fraction 8 in D. dasycarpus by this conventional chemical separation, so the target analysis method combined LC-MS guided-separation of quinoline alkaloids from fraction 8 was established. MS/MS fragmentation patterns of eight quinoline alkaloids reference standard compounds 1-8 were studied by ultra-performance liquid chromatography-electrospary ionization-mass spectrometry (UPLC-ESI-MS/MS). Based on the feature fragment ion 200, the parent ion scan mode was established for the target analysis of quinoline alkaloids in fraction 8. Finally, 8-methoxyflindersine (9) and N-metilatanina (10) were discovered and isolated quickly from fraction 8 guided by LC-MS, and their structures were identified by NMR and MS. Among them, compound 10 was isolated from the genus Dictamnus for the first time. These results indicated that this method is not only quick and sensitive for analyzing the quinoline alkaloids, but also to effectively guided-separate this kind of alkaloids in the root barks of D. dasycarpus.
Alkaloids ; isolation & purification ; Chromatography, High Pressure Liquid ; Dictamnus ; chemistry ; Ions ; Phytochemicals ; isolation & purification ; Plant Roots ; chemistry ; Quinolines ; isolation & purification ; Spectrometry, Mass, Electrospray Ionization ; Tandem Mass Spectrometry

The ocean continues to provide a plethora of unique scaffolds capable of remarkable biological applications. A large number of pyrroloiminoquinone alkaloids, including discorhabdins, epinardins, batzellines, makaluvamines, and veiutamine, have been isolated from various marine organisms. A class of pyrroloiminoquinone-related alkaloids, known as bispyrroloquinones, is the focus of this review article. This family of marine alkaloids, which contain an aryl substituted bispyrroloquinone ring system, includes three subclasses of alkaloids namely, wakayin, tsitsikammamines A-B, and zyzzyanones A-D. Both wakayin and the tsitsikammamines contain a tetracyclic fused bispyrroloiminoquinone ring system, while zyzzyanones contain a fused tricyclic bispyrroloquinone ring system. The unique chemical structures of these marine natural products and their diverse biological properties, including antifungal and antimicrobial activity, as well as the potent, albeit generally nonspecific and universal cytotoxicities, have attracted great interest of synthetic chemists over the past three decades. Tsitsikammamines, wakayin, and several of their analogs show inhibition of topoisomerases. One additional possible mechanism of anticancer activity of tsitsikammamines analogs that has been discovered recently is through the inhibition of indoleamine 2, 3-dioxygenase, an enzyme involved in tumoral immune resistance. This review discusses the isolation, synthesis, and evaluation of bioactivities of bispyrroloquinone alkaloids and their analogs.
Alkaloids ; chemistry ; pharmacology ; Animals ; Anti-Infective Agents ; chemistry ; pharmacology ; Antineoplastic Agents ; chemistry ; pharmacology ; Biological Products ; chemistry ; pharmacology ; Humans ; Indole Alkaloids ; chemistry ; pharmacology ; Indoles ; chemistry ; pharmacology ; Pyrroles ; chemistry ; pharmacology ; Quinolines ; chemistry ; pharmacology ; Quinones ; chemistry ; pharmacology

AIM: To investigate the quinoline alkaloids from the roots of Dictamnus angustifolius G.Don ex Sweet (Rutaceae). METHOD: The quinoline alkaloids were isolated by various column chromatographic methods and their structures were elucidated on the basis of spectral analysis. RESULTS: A new quinoline alkaloid, 5-methoxylrobustine (1), along with five known quinoline alkaloids were obtained, and their structures were identified as dictamnine (2), robustine (3), isopteleine (4), γ-fagarine (5), and skimmianine (6). Cytotoxicity testing of these alkaloids showed that all of them had weak cytotoxic activities against human breast cancer cells (MCF7). CONCLUSION Compound 1 is a new quinoline alkaloid. Alkaloid 3 showed stronger anti-proliferation effect than the other alkaloids.
Antineoplastic Agents, Phytogenic ; isolation & purification ; pharmacology ; therapeutic use ; Breast Neoplasms ; drug therapy ; Cell Line, Tumor ; Dictamnus ; chemistry ; Humans ; Hydroxyquinolines ; chemistry ; isolation & purification ; pharmacology ; therapeutic use ; Molecular Structure ; Phytotherapy ; Plant Extracts ; chemistry ; pharmacology ; therapeutic use ; Plant Roots ; chemistry ; Quinolines ; chemistry ; isolation & purification ; pharmacology ; therapeutic use

A series of quinoline-polyamine conjugates (8a-8n) were designed, synthesized and evaluated as inhibitors of cholinesterases (ChEs). Some of these compounds had potent ChEs inhibitory activity with IC50 values at micromolar range. Compound 8n exhibited the strongest inhibition on acetylcholinesterase (AChE) with an IC50 value of 8.78 micromol x L(-1), and compound 8i showed the most potent inhibition on butyrylcholinesterase (BChE) with IC50 value of 1.60 micromol x L(-1) which was slightly better than rivastigmine. The structure-activity relationship revealed that the chain length of polyamine and linker played important roles for inhibitory activity. Molecular modeling studies showed that 8i targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of cholinesterases.
Acetylcholinesterase ; metabolism ; Butyrylcholinesterase ; metabolism ; Cholinesterase Inhibitors ; chemical synthesis ; chemistry ; pharmacology ; Drug Design ; Inhibitory Concentration 50 ; Polyamines ; chemical synthesis ; chemistry ; pharmacology ; Quinolines ; chemical synthesis ; chemistry ; pharmacology ; Structure-Activity Relationship

Liver X receptor (LXR), a member of the superfamily of nuclear receptors, plays an important role in the activation of transcription factors involved in cholesterol metabolism, glucose homeostasis inflammation and lipogenesis. It is shown that LXR agnoists have the potentiality to be used as drugs for the prevention and treatment of atherosclerosis, which is its best investigated therapeutic indication. There are many compounds being studied in preclinical evaluation and biological assay. This paper will review briefly the LXR agonists in recent years.
ATP-Binding Cassette Transporters ; metabolism ; Amines ; chemical synthesis ; chemistry ; pharmacology ; Animals ; Atherosclerosis ; drug therapy ; metabolism ; Benzimidazoles ; chemical synthesis ; chemistry ; pharmacology ; Cholesterol ; analogs & derivatives ; pharmacology ; Glucose ; analogs & derivatives ; pharmacology ; Humans ; Lipid Metabolism ; Lipogenesis ; Liver X Receptors ; Orphan Nuclear Receptors ; agonists ; physiology ; Quinolines ; chemical synthesis ; chemistry ; pharmacology ; Sterol Regulatory Element Binding Protein 1 ; metabolism

This study is designed to investigate the effects of chinfloxacin hydrochloride (CFX) on the kinetics of HERG K+ channel. Whole cell patch clamp technique was used to record HERG K+ currents from HEK293 cells transiently transfected with cgi-HERG-GFP plasmids and channel kinetics were assessed in the absence and presence of CFX and moxifloxacin hydrochloride (MOX). Results demonstrated that the open state of HERG K+ channel was inhibited by CFX in a concentration- and time-dependent manner, with an IC50 of 162.1 +/- 14.2 micromol x L(-1), two folds higher than its positive control MOX. But there were no significant effects on channel kinetics. In addition, the inhibitory effect of CFX on HERG was enhanced when cells were subjected to altered extracellular K+ concentration.
Anti-Bacterial Agents ; administration & dosage ; chemistry ; pharmacology ; Aza Compounds ; pharmacology ; Dose-Response Relationship, Drug ; Ether-A-Go-Go Potassium Channels ; antagonists & inhibitors ; physiology ; Fluoroquinolones ; administration & dosage ; chemistry ; pharmacology ; HEK293 Cells ; Humans ; Inhibitory Concentration 50 ; Kinetics ; Molecular Structure ; Patch-Clamp Techniques ; Potassium ; pharmacology ; Quinolines ; pharmacology ; Time Factors ; Transfection

OBJECTIVETo investigate effects of Akt and ERK1/2 signaling pathways on waltonitone (WT) induced cell growth inhibition in human hepatocellular carcinoma BEL-7402 cells.

METHODCell viability of BEL-7402 cells was examined using MTT assay. Phosphorylation of E Akt and RK1/2 were detected by Western blot analysis, while cell cycle distribution of BEL7402 cells was analyzed by flow cytometry.

RESULTWT could inhibit the BEL-7402 cells growth, induce the S-phase cell cycle arrest, activate Akt and ERK1/2 phosporylation. Moreover, the cell growth inhibition and S-phase cell cycle arrest induction of WT on BEL-7402 cells could be blocked by Akt and ERK1/2 inhibitors.

CONCLUSIONWT induce the cell cycle arrest and inhibit the cell growth on BEL-7402 cells by modulating Akt and ERK1/2 phosphorylation.

Blotting, Western ; Carcinoma, Hepatocellular ; drug therapy ; metabolism ; Cell Line, Tumor ; Drugs, Chinese Herbal ; chemistry ; therapeutic use ; Flow Cytometry ; Humans ; Liver Neoplasms ; drug therapy ; metabolism ; Mitogen-Activated Protein Kinase 1 ; metabolism ; Mitogen-Activated Protein Kinase 3 ; metabolism ; Molecular Structure ; Phosphorylation ; drug effects ; Proto-Oncogene Proteins c-akt ; metabolism ; Quinolines ; chemistry ; therapeutic use

A series of N-(3-cyano-6-methyl-4-anilinoquinoline-7-yl) amide derivatives 13a-13n have been synthesized, their structures were confirmed with 1H NMR, EI-MS, IR and elemental analysis. Antitumor activities of all the synthesized compounds in vitro were tested with MTT. Compound 13j showed better than or equal antitumor activity on Bosutinib and EKB-569.
Aniline Compounds ; chemical synthesis ; chemistry ; pharmacology ; Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; Cell Line, Tumor ; Humans ; Quinolines ; chemical synthesis ; chemistry ; pharmacology