SYNTHESIS, ANTIRADICAL AND ANTIMICROBIAL ACTIVITY OF 6-[(AZAHETEROCYCLIL(ARYLAMINO)ETHYL]-3-R-2H-[1,2,4]TRIAZINO[2,3-C]QUINAZOLINE-2-ONES
DOI:
https://doi.org/10.11603/1811-2471.2024.v.i4.14980Keywords:
[1,2,4]triazino[2,3-c]quinazolines, azaheterocycles, anilines, linker group, antimicrobial and antifungal activity, antiradical activityAbstract
SUMMARY. The aim – to focus on the search for biologically active compounds among 6-substituted 3-R1-2H-[1,2,4]triazino[2,3-c]quinazoline-2-ones, which combine in their structure a condensed heterocyclic system and "pharmacophoric" saturated azaheterocycles (piperidine, piperazine, azepine) or substituted anilines connected via an ethyl linker group.
Material and Methods. Conventional methods of preparative organic chemistry were used to obtain the target compounds. Their purity and structure were confirmed by elemental analysis, HPLC-MS, and 1H NMR spectroscopy. To evaluate the antimicrobial and antifungal potential of 6-[(azaheterocyclil-(arylamino)-ethyl]-3-R1-2H-[1,2,4]triazino[2,3-c]quinazolin-2-ones, test cultures of bacteria Escherichia coli, Staphylococcus aureus, Mycobacterium luteum, and fungi Candida tenuis, Aspergillus niger were used. The minimum inhibitory concentration (MIC), bactericidal concentration (MBC), and fungicidal concentration (MFC) were determined using the serial dilution method. The antiradical activity was studied using a DPPH radical scavenging model.
Results. The reaction of 6-(1-chloroethyl)-3-R1-2H-[1,2,4]triazino[2,3-c]quinazolin-2-ones with saturated azacycles or anilines yielded a series of 6-[(azacyclic-(arylamino)-ethyl]-3-R1-2H-[1,2,4]triazino[2,3-c]quinazolin-2-ones, which demonstrated satisfactory predicted toxicity, pharmacokinetic parameters, and compliance with major drug-likeness criteria. Antimicrobial screening revealed that the synthesized compounds were practically inactive against Escherichia coli, Staphylococcus aureus, Candida tenuis, and Aspergillus niger. However, compounds 2.3 and 3.1 exhibited moderate antibacterial activity against Mycobacterium luteum. Among the synthesized compounds, only 6-(1-((4-fluorophenyl)amino)ethyl)-3-methyl-2H-[1,2,4]triazino[2,3-c]quinazoline-2-one revealed significant DPPH-radical scavenging activity.
Conclusions. Alkylation products of saturated azaheterocycles and anilines with 6-(1-chloroethyl)-3-R1-2H-[1,2,4]triazino[2,3-c]quinazolin-2-ones exhibit satisfactory predicted toxicity values and pharmacokinetic parameters. Some of the synthesized compounds show moderate antibacterial activity against Mycobacterium luteum and antiradical activity.
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