Evaluation of Antiseptic Drug Candidate Pyridosept in Preclinical in Vitro Studies.

Introduction: This work provides preclinical in vitro studies of an innovative antimicrobial agent named pyridosept, belonging to the quaternary bis-ammonium salts and synthesized on the base of pyridoxine. Since the wide spread of pathogens with tolerance to both antibiotics and antiseptics challenges the development of new antimicrobials providing high efficiency against fungi and microorganisms with multiple resistance.

Method: This work presents in vitro studies of pyridosept, such as antibacterial and anti-fungal activities (determination of minimal inhibitory concentration and quantitative suspension test method), as well as antibacterial activity of metal surface test, sporicidal and spermicidal activities, formation of resistance (to bacteria and fungi), Skin-PAMPA (study of membrane transdermal permeability), mutagenicity assays (in Ames test and OS-chromotest), cytotoxicity (MTT-assay) and comet assay in human skin fibroblasts.

Synthesis and biological evaluation of fluoroquinolones containing a pyridoxine derivatives moiety.

We report herein the design, synthesis and biological evaluation of series of 7-substituted fluoroquinolones with pyridoxine derivatives. In vitro screening of antibacterial activity and toxicity of 39 synthesized fluoroquinolones defined compounds 7 and 28 as lead compounds for further investigations. On various clinical isolates lead compounds 7 and 28 exhibited antibacterial activity comparable with reference fluoroqinolones.

Synthesis, antitumor activity and structure-activity studies of novel pyridoxine-based bioisosteric analogs of estradiol.

A new efficient approach to the synthesis of 6-alkenyl substituted pyridoxine derivatives has been developed. A series of 31 novel alkenyl pyridoxine derivatives, stilbene-based bioisosteric analogs of estradiol, were synthesized. In vitro cytotoxicity of the obtained compounds against MCF-7 (ER+) breast cancer tumor cells was studied using the MTT assay.

Novel Bis-Ammonium Salts of Pyridoxine: Synthesis and Antimicrobial Properties.

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.

In-vitro antitumor activity of new quaternary phosphonium salts, derivatives of 3-hydroxypyridine.

This work presents the results of in-vitro biological activity studies of three novel anticancer agents, phosphonium salts based on the 3-hydroxypyridine scaffold, including one derivative of 4-deoxypyridoxine. Proliferation and viability of cells treated with these compounds was assessed by the colony formation and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays. Effects of the compounds on apoptosis and cell cycle were studied by flow cytometry using annexin V-FITC/propidium iodide and propidium iodide staining, respectively.

Author Correction: Pyridoxine dipharmacophore derivatives as potent glucokinase activators for the treatment of type 2 diabetes mellitus.

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Pyridoxine dipharmacophore derivatives as potent glucokinase activators for the treatment of type 2 diabetes mellitus.

Glucokinase is one of the promising targets for glucose-lowering agents, and the development of GK activators are now considered as one of the most promising strategies for the treatment of type 2 diabetes mellitus. In this work, a series of novel symmetric molecular constructs, in which two pyridoxine moieties are connected via sulfur-containing linkers, have been synthesized and tested in vitro for glucokinase activation potential. The enzyme activation rates by two most active compounds at 100 μM (~150% and 130%) were comparable to that of the reference agent PF-04937319 (~154%).

Synthesis and Antibacterial Activity of Novel Quaternary Ammonium Pyridoxine Derivatives.

A series of 26 quaternary ammonium pyridoxine derivatives were synthesized and their cytotoxicity and antibacterial activities against clinically relevant bacterial strains were tested in vitro. The antibacterial activity of mono-ammonium salts increased with the rise of the lipophilicity and compound 3,3,5-trimethyl-8,8-dioctyl-1,7,8,9-tetrahydro-[1,3]dioxino[5,4-d]pyrrolo[3,4-b]pyridin-8-ium chloride (2d) reaches a maximum among them. Bis-ammonium salt of pyridoxine 4 with two dimethyloctylamine groups also demonstrated high antibacterial activity despite lower lipophilicity.

Bis-phosphonium salts of pyridoxine: the relationship between structure and antibacterial activity.

A series of 23 novel bis-phosphonium salts based on pyridoxine were synthesized and their antibacterial activities were evaluated in vitro. All compounds were inactive against gram-negative bacteria and exhibited the structure-dependent activity against gram-positive bacteria. The antibacterial activity enhanced with the increase in chain length at acetal carbon atom in the order n-Pr>Et>Me.

Synthesis and antibacterial activity of novel phosphonium salts on the basis of pyridoxine.

A series of 13 phosphonium salts on the basis of pyridoxine derivatives were synthesized and their antibacterial activity against clinically relevant strains was tested in vitro. All compounds were almost inactive against gram-negative bacteria and exhibited structure-dependent activity against gram-positive bacteria. A crucial role of ketal protection group in phosphonium salts for their antibacterial properties was demonstrated.