Antifungal Activity of N-Arylbenzoquinaldinium Derivatives against a Clinical Strain of M. canis.

Background: Microsporum canis (Bodin, 1902) is a dermatophyte, which is widely represented in the developing and the developed world alike. Commonly transmitted from domestic animals it is particularly dangerous for immunosuppressed patients due to AIDS, cancer or transplant surgery. Search for new perspective antimycotic derivatives becomes an urgent task in the disease containment. Previously, several quinolinium analogs were screened for their antibacterial activity (E. coli, St. aurous) by our research team. Furthermore, some N-phenylbenzoquinaldinium derivatives have shown antifungal activity against Candida albicans and Candida krusei. Aims: In this study, we sought to investigate fungicidal properties of N-arylbenzoquinaldinium derivatives against a clinical strain of Microsporum canis for future medicinal applications. Materials and Methods: N-phenyl-[f]-benzoquinaldinium salts were prepared by a variation of the previously described technique and tested against a clinical strain of the fungus of Microsporum canis 114 harvested from pathogenic material of a patient (Perm, Russia, 2014). Results: N-phenyl-[f]-benzoquinaldinium tetrafluoroborate has shown antifungal activity par to (or exceeding) that of commercially available medication. Moreover, this benzoquinaldinium analog can be potentially labelled with tritium by our nuclear-chemical method, making it amenable for the sensitive pharmacokinetic studies. Conclusions: N-phenyl-[f]-benzoquinaldinium tetrafluoroborate has been shown as a promising compound for the further development of potent antifungal agents as well as radiotracers for further elucidation of biological pathways of antifungal activity.

Pathways of ion-molecular interactions of nucleogenic phenyl cations with the nucleophilic centers of picolines.

BACKGROUND: The nuclear-chemical method brought unique opportunity for synthesis of unknown and hardly available organic compounds. Presence of tritium labeling allows one-step preparation of radioactive markers for the investigation of chemical and biological processes. METHODS: The ion-molecular reactions of nucleogenic phenyl cations with 4-picoline have been carried out. The phenyl cations were generated by spontaneous tritium ß-decay within the tritium-labeled benzene. Both additions to the nitrogen and substitutions about the aromatic ring were able to be studied simultaneously. RESULTS: Unusual substitutions on both the α- and ß-positions of the ring system have been revealed. CONCLUSION: By unknown direct phenylation of nitrogen atom tritium-labeled N-phenylpicolinium derivatives, perspective biological markers have been synthesized.

New way of direct nitrogen atom phenylation in quinoline derivatives.

Comparison of ion-molecular reactions of free-phenyl cations generated by tritium ß -decay with 2-methyl- and 2-phenylquinolines has been investigated. The reaction of direct nitrogen atom phenylation with the help of nucleogenic phenyl cations has been fulfilled for the first time and a new one-step synthesis of tritium-labeled N-phenyl-2-phenylquinolinium salt-lipophilic radioactive biological marker has been elaborated.