2-([1,2,4]triazolo[1,5-c]quinazolin-2-yl-)alkyl-(alkaryl-, aryl-)-amines and their derivatives. (3Н-quinazolin-4-yliden)hydrazides (1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)alkyl-(alkaryl-, aryl-)carboxylic acids: features of synthesis, modification and ant

Authors

  • Yu. V. Martynenko Zaporizhzhia State Medical University,
  • M. S. Kazunin Zaporizhzhia State Medical University,
  • E. А. Selivanova Zaporizhzhia State Medical University,
  • S. I. Kovalenko Zaporizhzhia State Medical University,

DOI:

https://doi.org/10.14739/2310-1210.2016.4.79709

Keywords:

Aminoacіds, (1, 3-dioxo-1, 3-dihydro-2H-isoindol-2-yl)alkyl-(alkaryl-, aryl-)carboxylic acids, (3Н-quinazolin-4-yliden)hydrazides, 2-substituted [1, 2, 4]triazolo[1, 5-c]quinazolines, Antimicrobial And Antifungal Activity

Abstract

The combination of different «pharmacophore» components in one structure connected via «linker» functional groups is one of the major and justified approaches for the synthesis of new biologically active substances. In this area (3Н-quinazoline-4-yliden)hydrazides (1,3-dioxo-1,3-dihydro-2H-іsoindol-2-yl-)alkyl-(aralkyl-, aryl-)carboxylic acids are the most interesting compounds. They contain quinazoline and іsoindole fragments united through аlkyl, аlkaryl and аryl groups and furthermore can be used for the synthesis of new heterocycles.


Aim: The purpose of this work is to find antimicrobial and antifungal agents among (3H-quinazolin-4-ylidene)hydrazides (1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl-)alkyl-(alkaryl-, aryl-)carboxylic acids and their fused derivatives and to establish physical-chemical properties of these compounds and to correlate «structure – activity relationship» for structure optimization.


Methods and results. The study of microbiological activity was conducted by disco-diffusion method on Mueller-Hinton agar on the following strains of microorganisms: gram-positive cocci (Staphylococcus aureus ATCC 25923, Enterococcus aeruginosa, E. faecalis ATCC 29212), gram-negative bacteria (Pseudomonas aeruginosa PSS27853, Escherichia coli ATCC 25922), facultative anaerobic gram-negative bacteria (Klebsiella pneumoniaе) and fungi (Candida albicans ATCC 885653).


Conclusion. The protected aminoacids were used to synthesize unknown (3H-quinazolin-4-ylidene)hydrazides (1,3-dioxo-1,3-dihydroisoindolo-2-yl-)alkyl-(alkaryl-, aryl-)carboxylic acids in the reactions of nucleophilic substitution for the first time. While new [1,2,4]triazolo[1,5-c]quinazolin-2-yl-alkyl-(alkaryl-, aryl-)- isoindol-1,3(2H)-diones were received by heterocyclization of the last. Structure and identity have been confirmed by elemental analysis, physical and chemical methods (1H NMR spectroscopy, mass-spectrometry). Analysis of the results of microbiological study shows, that the synthesized compounds have never been active against St. aureus, E. aerogenes, P. aeruginosa, E. coli, K. pneumoniaе (growth inhibition zone 6 mm). However, compounds 2.1, 2.2 are found among the (3H-quinazoline-4-ylidene)hydrazides (1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl-)alkyl-(aralkyl-, aryl-)carboxylic acids (2.1–2.9) and inhibit the growth of E. faecalis zone 7 mm. Conducted cyclocondensation of 2.1–2.9 compounds does not lead to increase of antibacterial activity of corresponding [1,2,4]triazolo[1,5-c]quinazoline-2-yl-alkyl-(alkaryl-, aryl-)-isoindol-1,3(2H)-diones (3.1–3.9) against E. faecalis. Thus, the antibacterial effect against E. faecalis is characteristic only for compounds 3.2, 3.3 and 3.4 (growth inhibition zone 7 mm) and is slightly lower than the corresponding activity of ampicillin.

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Martynenko YV, Kazunin MS, Selivanova EА, Kovalenko SI. 2-([1,2,4]triazolo[1,5-c]quinazolin-2-yl-)alkyl-(alkaryl-, aryl-)-amines and their derivatives. (3Н-quinazolin-4-yliden)hydrazides (1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)alkyl-(alkaryl-, aryl-)carboxylic acids: features of synthesis, modification and ant. Zaporozhye Medical Journal [Internet]. 2016Oct.13 [cited 2024Nov.2];18(4). Available from: http://zmj.zsmu.edu.ua/article/view/79709

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Problems of pharmacy