2-([1,2,4]triazolo[1,5-c]quinazoline-2-yl-)alkyl-(alkaryl-,aryl-)-amines and their derivatives. Message 2. The synthesis of (3Н-quinazoline-4-ylidene)hydrazides N-protected aminoacids, using a variety of amine-protecting approaches. Physical-chemical prop

Authors

  • Yu. V. Martynenko Zaporizhzhia State Medical University, Ukraine,
  • M. S. Kazunin Zaporizhzhia State Medical University, Ukraine,
  • I. S. Nosulenko Zaporizhzhia State Medical University, Ukraine,
  • G. G. Berest Zaporizhzhia State Medical University, Ukraine,
  • S. І. Kоvalenko Zaporizhzhia State Medical University, Ukraine,
  • O. M. Kamyshnyi Zaporizhzhia State Medical University, Ukraine,
  • N. M. Polishchuk Zaporizhzhia State Medical University, Ukraine,

DOI:

https://doi.org/10.14739/2310-1210.2018.3.130544

Keywords:

N-protected aminoacids, carbonyldiimidazoles synthesis, (3Н-quinazoline-4-ylidene)hydrazides, physical-chemical properties, spectral features, biological activity

Abstract

The synthetic potential of (3H-quinazoline-4-ylidene)hydrazides of carboxylic acids is significant in the context of new s-triazoloquinazolines creation and the obtained data of biological activity is a valid reason for the development of new methods of their synthesis, using a variety of reagents. The introduction of N-protected aminoacids moieties into 4-hydrazinoquinazoline molecule is an important aspect, which solves this problem and extends the limits of hydrazides usage. The above would allow to change physical-chemical and biological properties of the corresponding hydrazides and it opens new perspectives of their practical application and further chemical transformations.

The aim of the work is synthesis of unknown (3H-quinazoline-4-ylidene)hydrazides of N-protected aminoacids, using various approaches of the amino group protection, research of structure features and finding effective biologically active substances with antimicrobial and antiradical activities among them.

Materials and methods. The individuality and structure of synthesized compounds was proved by elemental analysis, chromatomass- and 1H NMR spectra. In vitro research of antiradical activity was based on the interaction of synthesized compounds with 2,2-diphenyl-1-picrylhydrazyl (DPPH). The study of microbiological activity was conducted by serial dilution method on Mueller–Hinton broth on following strains of microorganisms and fungi: St. aureus ATCC 25923, E. coli ATCC 25922, P. aeruginosa ATCC 27853, C. albicans ATCC 885653.

Conclusions. A synthetic method for (3H-quinazoline-4-ylidene)hydrazides N-protected aminoacids, which was based on interaction of 4-hydrazinoquinazoline with “activated” N-protected aminoacids was elaborated. It was found, that benzoyl- and Boc-aminoacids were the most reliable substrates for the synthesis of the corresponding hydrazides. A detailed analysis of 1H NMR spectra allowed the unambiguous establishing of peculiar to (3H-quinazoline-4-ylidene)hydrazides N-protected aminoacids amid-imide tautomerism in DMSO solutions, due to the presence of hydrazide and amide groups. The microbiological screenings showed that hydrazides exhibited moderate antimicrobial activity against P. aeruginosa (MIC 50–100 µg/ml and MBC 100 µg/ml) and fungal activity against C. albicans (MIC 50 µg/ml, MBC 50–100 µg/ml). In addition, the synthesized compounds exhibited high antiradical activity, which indicated their prospects for further researches on other types of biological activity.

 

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1.
Martynenko YV, Kazunin MS, Nosulenko IS, Berest GG, Kоvalenko SІ, Kamyshnyi OM, Polishchuk NM. 2-([1,2,4]triazolo[1,5-c]quinazoline-2-yl-)alkyl-(alkaryl-,aryl-)-amines and their derivatives. Message 2. The synthesis of (3Н-quinazoline-4-ylidene)hydrazides N-protected aminoacids, using a variety of amine-protecting approaches. Physical-chemical prop. Zaporozhye medical journal [Internet]. 2018May30 [cited 2024Apr.24];(3). Available from: http://zmj.zsmu.edu.ua/article/view/130544

Issue

No. 3 (2018)

Section

Problems of pharmacy

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