NP04634 prevents cell damage caused by calcium overload and mitochondrial disruption in bovine chromaffin cells

Valero, Teresa; Barrio, Laura; Egea, Javier; Cañas, Noelia; Martı́nez, Ana; Garcı́a, Antonio G.; Villarroya, Mércedes; López, Manuela G.

doi:10.1016/j.ejphar.2009.02.021

Cited by 12 publications

(9 citation statements)

References 33 publications

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“…Specifically, 180 protects neurons from toxicity induced by 30K + /5Ca 2+ /FPL at a concentration of 10 μM, reduces voltage dependent Ca 2+ levels and protects mitochondrial disruption by preventing depolarization. 395 …”

Section: Modulators Of Ion Channelsmentioning

confidence: 99%

Natural products as a source of Alzheimer's drug leads

2011

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Section: Modulators Of Ion Channelsmentioning

confidence: 99%

Natural products as a source of Alzheimer's drug leads

2011

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“…In the pre-incubation experiment, it could be assessed whether the compounds have cytoprotective properties due to the activation of endogenous antioxidant pathways. In the co-incubation could be shown whether compounds are free-radical scavengers [42,[80][81][82]. MTT assay was a test of choice, because in this assay mitochondrial activity is measured.…”

Section: Cytoprotection Against Oxidative Stressmentioning

confidence: 99%

Novel tetrahydroacridine derivatives with iodobenzoic moieties induce G0/G1 cell cycle arrest and apoptosis in A549 non-small lung cancer and HT-29 colorectal cancer cells

et al. 2019

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A series of nine tetrahydroacridine derivatives with iodobenzoic moiety were synthesized and evaluated for their cytotoxic activity against cancer cell lines-A549 (human lung adenocarcinoma), HT-29 (human colorectal adenocarcinoma) and somatic cell line-EA.hy926 (human umbilical vein cell line). All compounds displayed high cytotoxicity activity against A549 (IC 50 59.12-14.87 µM) and HT-29 (IC 50 17.32-5.90 µM) cell lines, higher than control agents-etoposide and 5-fluorouracil. Structure-activity relationship showed that the position of iodine in the substituent in the para position and longer linker most strongly enhanced the cytotoxic effect. Among derivatives, 1i turned out to be the most cytotoxic and displayed IC 50 values of 14.87 µM against A549 and 5.90 µM against HT-29 cell lines. In hyaluronidase inhibition assay, all compounds presented anti-inflammatory activity, however, slightly lower than reference compound. ADMET prediction showed that almost all compounds had good pharmacokinetic profiles. 1b, 1c and 1f compounds turned out to act against chemoresistance in cisplatin-resistant 253J B-V cells. Compounds intercalated into DNA and inhibited cell cycle in G0/G1 phase-the strongest inhibition was observed for 1i in A549 and 1c in HT-29. Among compounds, the highest apoptotic effect in both cell lines was observed after treatment with 1i. Compounds caused DNA damage and H2AX phosphorylation, which was detected in A549 and HT-29 cells. All research confirmed anticancer properties of novel tetrahydroacridine derivatives and explained a few pathways of their mechanism of cytotoxic action.

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“…The development of many drugs interacting with ion channels was terminated (in alphabetical order): DMP- 543 [138] and an increase of parietal regional cerebral blood flow in AD patients [139], the clinical results were disappointing [140]), MEM-1003 (BAY-Z-4406, Memory Pharmaceuticals under license from Bayer; a L-type voltage-gated calcium channel [141]), nerispirdine (HP-184, Hoechst, now sanofi; an inhibitor of Mtype K + channels), nicardipine (YC-93, Yamanouchi [142]), nifedipine (BAY-A-1040, Adalat, Bayer [143]), nimodipine (BAY-E-9736, Nimotop, Bayer [144][145][146][147][148][149][150][151][152]), nitrendipine (BAY-E-5009; Bayotensin, Bayer; all L-type voltage-gated calcium channels [153,154]), NP-34 (NP-04634; Noscira, formerly Neuropharma; a dual calcium channel blocker and acetylcholinesterase inhibitor [155]), NS-649 (Neu-roSearch; a neuron-specific calcium channel blocker [156]), NSD-761 (NeuroSearch; a selective ion channel modulator); RGH-2716 (TDN-345; a nootropic neuroselective ion channel blocker; Takeda in collaboration with Gedeon Richter [157][158][159]), SNX-482 (R-type calcium channel blocker of Neurex, now Elan Pharmaceuticals [160][161][162]), SPI-017 (Sucampo; selective type-2 chloride channel activator), tamolarizine (NC-1100, calcium channel blocker, Nippon Chemiphar [163][164][165]), VRX-698 (Valeant Pharmaceuticals International; a potassium channel opener), and XE-991 (Bristol-Myers Squibb; a KCNQ potassium channel blocker [166,167]).…”

Section: Drugs Interacting With Ion Channels (Non-receptors)mentioning

confidence: 99%

Cognitive Enhancers (Nootropics). Part 3: Drugs Interacting with Targets other than Receptors or Enzymes. Disease-modifying Drugs

Froestl

Pfeifer

Muhs

2013

JAD

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Cognitive enhancers (nootropics) are drugs to treat cognition deficits in patients suffering from Alzheimer's disease, schizophrenia, stroke, attention deficit hyperactivity disorder, or aging. Cognition refers to a capacity for information processing, applying knowledge, and changing preferences. It involves memory, attention, executive functions, perception, language, and psychomotor functions. The term nootropics was coined in 1972 when memory enhancing properties of piracetam were observed in clinical trials. In the meantime, hundreds of drugs have been evaluated in clinical trials or in preclinical experiments. To classify the compounds, a concept is proposed assigning drugs to 19 categories according to their mechanism(s) of action, in particular drugs interacting with receptors, enzymes, ion channels, nerve growth factors, re-uptake transporters, antioxidants, metal chelators, and disease modifying drugs, meaning small molecules, vaccines, and monoclonal antibodies interacting with amyloid-β and tau. For drugs, whose mechanism of action is not known, they are either classified according to structure, e.g., peptides, or their origin, e.g., natural products. The review covers the evolution of research in this field over the last 25 years.

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NP04634 prevents cell damage caused by calcium overload and mitochondrial disruption in bovine chromaffin cells

Cited by 12 publications

References 33 publications

Natural products as a source of Alzheimer's drug leads

Natural products as a source of Alzheimer's drug leads

Novel tetrahydroacridine derivatives with iodobenzoic moieties induce G0/G1 cell cycle arrest and apoptosis in A549 non-small lung cancer and HT-29 colorectal cancer cells

Cognitive Enhancers (Nootropics). Part 3: Drugs Interacting with Targets other than Receptors or Enzymes. Disease-modifying Drugs

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