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Molecules (Basel, Switzerland) Sep 2020A series of 108 novel quaternary bis-ammonium pyridoxine derivatives carrying various substituents at the quaternary nitrogen's and acetal carbon was synthesized....
A series of 108 novel quaternary bis-ammonium pyridoxine derivatives carrying various substituents at the quaternary nitrogen's and acetal carbon was synthesized. Thirteen compounds exhibited antibacterial and antifungal activity (minimum inhibitory concentration (MIC) 0.25-16 µg/mL) comparable or superior than miramistin, benzalkonium chloride, and chlorhexidine. A strong correlation between the lipophilicity and antibacterial activity was found. The most active compounds had logP values in the range of 1-3, while compounds with logP > 6 and logP < 0 were almost inactive. All active compounds demonstrated cytotoxicity comparable with miramistin and chlorhexidine on HEK-293 cells and were three-fold less toxic when compared to benzalkonium chloride. The antibacterial activity of leading compound on biofilm-embedded , , or was comparable or even higher than that of the benzalkonium chloride. In vivo was considerably less toxic (LD 1705 mg/kg) than benzalkonium chloride, miramistine, and chlorhexidine at oral administration on CD-1 mice. An aqueous solution of (0.2%) was shown to be comparable to reference drugs efficiency on the rat's skin model. The molecular target of seems to be a cellular membrane as other quaternary ammonium salts. The obtained results make the described quaternary bis-ammonium pyridoxine derivatives promising and lead molecules in the development of the new antiseptics with a broad spectrum of antimicrobial activity.
Topics: Ammonium Compounds; Anti-Infective Agents; Biofilms; Chemistry Techniques, Synthetic; HEK293 Cells; Humans; Microbial Sensitivity Tests; Pyridoxine; Salts; Structure-Activity Relationship
PubMed: 32971844
DOI: 10.3390/molecules25184341 -
The American Journal of Clinical... Dec 2022
Topics: Adult; Humans; Riboflavin Deficiency; Vitamin B 6; Riboflavin; Pyridoxine; Genotype; Vitamins; Methylenetetrahydrofolate Reductase (NADPH2)
PubMed: 36264295
DOI: 10.1093/ajcn/nqac269 -
British Medical Journal (Clinical... Oct 1985
Topics: Abnormalities, Drug-Induced; Antiemetics; Dicyclomine; Doxylamine; Drug Combinations; Female; Humans; Infant, Newborn; Pregnancy; Pyridines; Pyridoxine; Risk; United Kingdom
PubMed: 3929963
DOI: 10.1136/bmj.291.6500.918 -
Neurology India 2018
Topics: Aldehyde Dehydrogenase; Humans; Infant; Mutation; Pyridoxine; Spasms, Infantile; Vitamin B Complex
PubMed: 29547149
DOI: 10.4103/0028-3886.227278 -
International Journal of Molecular... Aug 2020We investigated the effects of pyridoxine deficiency on ischemic neuronal death in the hippocampus of gerbil ( = 5 per group). Serum pyridoxal 5'-phosphate levels were...
We investigated the effects of pyridoxine deficiency on ischemic neuronal death in the hippocampus of gerbil ( = 5 per group). Serum pyridoxal 5'-phosphate levels were significantly decreased in Pyridoxine-deficient diet (PDD)-fed gerbils, while homocysteine levels were significantly increased in sham- and ischemia-operated gerbils. PDD-fed gerbil showed a reduction in neuronal nuclei (NeuN)-immunoreactive neurons in the medial part of the hippocampal CA1 region three days after. Reactive astrocytosis and microgliosis were found in PDD-fed gerbils, and transient ischemia caused the aggregation of activated microglia in the stratum pyramidale three days after ischemia. Lipid peroxidation was prominently increased in the hippocampus and was significantly higher in PDD-fed gerbils than in Control diet (CD)-fed gerbils after ischemia. In contrast, pyridoxine deficiency decreased the proliferating cells and neuroblasts in the dentate gyrus in sham- and ischemia-operated gerbils. Nuclear factor erythroid-2-related factor 2 (Nrf2) and brain-derived neurotrophic factor (BDNF) levels also significantly decreased in PDD-fed gerbils sham 24 h after ischemia. These results suggest that pyridoxine deficiency accelerates neuronal death by increasing serum homocysteine levels and lipid peroxidation, and by decreasing Nrf2 levels in the hippocampus. Additionally, it reduces the regenerated potentials in hippocampus by decreasing BDNF levels. Collectively, pyridoxine is an essential element in modulating cell death and hippocampal neurogenesis after ischemia.
Topics: Animals; Brain Ischemia; Brain-Derived Neurotrophic Factor; Cell Proliferation; Diet; Gerbillinae; Hippocampus; NF-E2-Related Factor 2; Neural Stem Cells; Neurons; Oxidative Stress; Pyridoxine
PubMed: 32759679
DOI: 10.3390/ijms21155551 -
Developmental Medicine and Child... Nov 2003A case report of neonatal onset pyridoxine-dependent seizures in a male patient with early diagnosis and treatment is presented. The patient's epilepsy was recognized... (Review)
Review
A case report of neonatal onset pyridoxine-dependent seizures in a male patient with early diagnosis and treatment is presented. The patient's epilepsy was recognized and treated with pyridoxine (vitamin B6) within 8 hours of birth. Treatment has been nearly continuous since that time. This paper reports the results of a full neuropsychological evaluation at age 37 years and MRI completed at age 31 years. Consistent with other case reports in the literature, there was a significant Performance IQ (PIQ) advantage with decreased Verbal IQ (VIQ) and expressive language skills (Full-Scale IQ 71, VIQ 64, PIQ 85). MRI demonstrated characteristic thinning of the posterior corpus callosum. This report provides an example of early treatment that nonetheless results in a mild mental retardation. The similarity of the structural changes on MRI and the cognitive profile of this patient to those of others reported in the literature suggest that the underlying mechanism for both may be the same.
Topics: Adult; Agenesis of Corpus Callosum; Anticonvulsants; Cognition Disorders; Electroencephalography; Epilepsy; Humans; Intellectual Disability; Magnetic Resonance Imaging; Male; Neuropsychological Tests; Pyridoxine; Severity of Illness Index
PubMed: 14580135
DOI: 10.1017/s0012162203001440 -
British Medical Journal Oct 1973
Topics: Dihydroxyphenylalanine; Humans; Nausea; Parkinson Disease; Pyridoxine
PubMed: 4758412
DOI: 10.1136/bmj.4.5886.236-b -
The Journal of Biological Chemistry Jan 1947
Topics: Amino Acids; Pyridoxine; Transaminases; Vitamin B 6 Deficiency
PubMed: 20281632
DOI: No ID Found -
European Review For Medical and... Jun 2022Nausea and vomiting of pregnancy is a common disease that affects many women suffering from mild to severe symptoms. Amongst the different treatments, a fixed dose...
OBJECTIVE
Nausea and vomiting of pregnancy is a common disease that affects many women suffering from mild to severe symptoms. Amongst the different treatments, a fixed dose combination of doxylamine and pyridoxine has been proven safe and effective although the mechanism of action is not well established. There are different pharmaceutical dosage forms in the European market. The objective of this study was to compare the characteristics of a capsule formulation, Cariban® and a tablet formulation, Xonvea® to evaluate the potential impact of their release profiles on their onset of action.
MATERIALS AND METHODS
10 mg/10 mg of doxylamine succinate/pyridoxine hydrochloride capsules (Cariban®) and tablets (Xonvea®) were used as reference materials. Appearance, mass, composition, and in vitro dissolution profiles were compared. Bibliographic data from 4 pharmacokinetic studies of Xonvea® and 1 pharmacokinetic study of Cariban® was reviewed.
RESULTS
In vitro dissolution studies showed significant differences in dissolution profiles of tablets and capsules. The later exhibiting some release of both drug substances in acid conditions followed by a non-complete release after a total of 3 hours while the tablets demonstrated gastro-resistant properties and rapid API release in about 20-30 minutes after the acid stage. Comparison of PK data showed greater Cmax for pyridoxine.
CONCLUSIONS
At pH 6.8, complete and faster release of the fixed dose combination for Xonvea® gastro-resistant tablets compared to Cariban® capsules could possibly explain the greater Cmax observed in vivo for the tablet's formulation. This could translate into faster onset of action and relief of nausea for pregnant women taking the tablets vs. the capsules.
Topics: Antiemetics; Doxylamine; Female; Gastrointestinal Agents; Humans; Nausea; Pregnancy; Pyridoxine; Solubility; Tablets
PubMed: 35776043
DOI: 10.26355/eurrev_202206_29081 -
Scientific Reports May 2022High concentration pyridoxal 5'-phosphate, the cofactor of vitamin B6, potentiates cytotoxicity in cancer cells exposed to 5-fluorouracil (FUra) and folinic acid (FA)....
High concentration pyridoxal 5'-phosphate, the cofactor of vitamin B6, potentiates cytotoxicity in cancer cells exposed to 5-fluorouracil (FUra) and folinic acid (FA). We studied the effect of high-dose pyridoxine on antitumor activity of regimens comprising FUra and FA in 27 advanced breast carcinoma patients. Of 18 previously untreated patients, 12 had tumors that did not overexpress HER2 (Group I), and 6 that overexpressed HER2 (Group II). Nine patients (Group III) had prior chemotherapy. Group I received AVCF (doxorubicin, vinorelbine, cyclophosphamide, FUra, FA) or FAC (doxorubicin, cyclophosphamide, FUra, FA) followed by TCbF (paclitaxel carboplatin, FUra, FA). Groups II, and III received TCbF. Pyridoxine iv (1000-3000 mg/day) preceded each FA and FUra. Group II also received trastuzumab and pertuzumab. 26 patients responded. Three patients in Group I had CRs and 9 had PRs with 62-98% reduction rates; 4 patients in Group II had CRs and 2 had PRs with 98% reduction. Of 7 measurable patients in Group III, 2 attained CRs, and 5 had PRs with 81-94% reduction rates. Median time to response was 3.4 months. Unexpected toxicity did not occur. This pilot study suggests that high-dose vitamin B6 enhances antitumor potency of regimens comprising FUra and FA.
Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Doxorubicin; Female; Fluorouracil; Humans; Leucovorin; Pilot Projects; Pyridoxine
PubMed: 35641554
DOI: 10.1038/s41598-022-12998-5