Six potential AChE reactivators were synthesized using modification of currently known synthetic pathways. Their potency to reactivate AChE inhibited by insecticide chlorpyrifos was tested in vitro. According to the results, (E)-1-(2-hydroxyiminomethylpyridinium)-4-(4-hydroxyiminomethylpyridinium)-but-2-ene dibromide seems to be the most potent AChE reactivator. The reactivation potency of these compounds depends on structural factors such as constitution of the linking chain between both pyridinium rings, position of the oxime moiety at the pyridinium ring and presence of quaternary nitrogens.

• MeSH
• acetylcholinesterasa metabolismus   MeSH
• bromované uhlovodíky chemická syntéza   farmakologie   MeSH
• cholinesterasové inhibitory farmakologie   MeSH
• dursban farmakologie   MeSH
• dusík chemie   MeSH
• krysa rodu Rattus MeSH
• oximy chemie   MeSH
• pyridinové sloučeniny chemická syntéza   farmakologie   MeSH
• reaktivátory cholinesterasy farmakologie   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• hodnotící studie MeSH
• práce podpořená grantem MeSH
• Názvy látek
• (E)-1-(2-hydroxyiminomethylpyridinium)-4-(4-hydroxyiminomethylpyridinium)-but-2-ene dibromide MeSH Prohlížeč
• acetylcholinesterasa MeSH
• bromované uhlovodíky MeSH
• cholinesterasové inhibitory MeSH
• dursban MeSH
• dusík MeSH
• oximy MeSH
• pyridinové sloučeniny MeSH
• reaktivátory cholinesterasy MeSH

In the present paper, we describe the synthesis of a new group of 5-hydroxyisoquinolinium salts with different lengths of alkyl side-chain (C10-C18), and their chromatographic analysis and biological assay for in vitro activity against bacterial and fungal strains. We compare the lipophilicity and efficacy of hydroxylated isoquinolinium salts with the previously published (non-hydroxylated) isoquinolinium salts from the point of view of antibacterial and antifungal versatility and cytotoxic safety. Compound 11 (C18) had to be excluded from the testing due to its low solubility. Compounds 9 and 10 (C14, C16) showed only moderate efficacy against G+ bacteria, notably with excellent potency against Staphyloccocus aureus, but no effect against G- bacteria. In contrast, non-hydroxylated isoquinolinium salts showed excellent antimicrobial efficacy within the whole series, particularly 14 (C14) against G+ strains and 15 (C16) against fungi. The electronic properties and desolvation energies of 5-hydroxyisoquinolinium and isoquinolinium salts were studied by quantum-chemistry calculations employing B3LYP/6-311++G(d,p) method and an implicit water-solvent simulation model (SCRF). Despite the positive mesomeric effect of the hydroxyl moiety reducing the electron density of the quaternary nitrogen, it is probably the higher lipophilicity and lower desolvation energy of isoquinolinium salts, which is responsible for enhanced antimicrobial versatility and efficacy.

• Klíčová slova
• 5-Hydroxyisoquinolinium salts, Antimicrobial activity, Isoquinolinium salts, Lipophilicity, Synthesis,
• MeSH
• antibakteriální látky chemická syntéza   farmakologie   MeSH
• antifungální látky chemická syntéza   farmakologie   MeSH
• gramnegativní bakterie účinky léků   růst a vývoj   MeSH
• grampozitivní bakterie účinky léků   růst a vývoj   MeSH
• houby účinky léků   růst a vývoj   MeSH
• isochinoliny chemická syntéza   farmakologie   MeSH
• kvantová teorie MeSH
• mikrobiální testy citlivosti MeSH
• molekulární modely MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antibakteriální látky MeSH
• antifungální látky MeSH
• isochinoliny MeSH

In this study, we report the synthesis, antibacterial and anticancer evaluation of 38 novel phenanthridines that were designed as analogs of the benzo[c]phenanthridine alkaloids. The prepared phenanthridines differ from the benzo[c]phenanthridines in the absence of a benzene A-ring. All novel compounds were prepared from 6-bromo-2-hydroxy-3-methoxybenzaldehyde in several synthetic steps through reduction of Schiff bases and accomplished by radical cyclization. Twelve derivatives showed high antibacterial activity against Bacillussubtilis, Micrococcusluteus and/or Mycobacteriumvaccae at single digit micromolar concentrations. Some compounds also displayed cytotoxicity against the K-562 and MCF-7 cancer cell lines at as low as single digit micromolar concentrations and were more potent than chelerythrine and sanguinarine. The active compounds caused cell-cycle arrest in cancer cells, increased levels of p53 protein and caused apoptosis-specific fragmentation of PARP-1. Biological activity was connected especially with the presence of the N-methyl quaternary nitrogen and 7-benzyloxy substitution (compounds 7i, 7j, 7k, and 7l) of phenanthridine.

• Klíčová slova
• antibacterial activity, antiproliferative, benzo[c]phenanthridines, phenanthridines, radical cyclization,
• MeSH
• antibakteriální látky chemická syntéza   chemie   farmakologie   MeSH
• Bacteria účinky léků   MeSH
• fenantridiny chemická syntéza   chemie   farmakologie   MeSH
• kontrolní body buněčného cyklu účinky léků   MeSH
• lidé MeSH
• mikrobiální testy citlivosti MeSH
• molekulární struktura MeSH
• nádorové buněčné linie MeSH
• proliferace buněk účinky léků   MeSH
• protinádorové látky chemická syntéza   chemie   farmakologie   MeSH
• techniky syntetické chemie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antibakteriální látky MeSH
• fenantridiny MeSH
• protinádorové látky MeSH