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.

 

References

Karpenko, O. V., & Kovalenko, S. I. (2005). Syntez 2-R-triazolo[1,5-c]hinazoliniv. Povidomlennia 1 [Synthesis of 2-R-triazolo[1,5-c]quinazolines. Message 1]. Zhurnal orhanichnoi ta pharmatsevtychnoi khimii, 3, 2(10), 47–54. [in Ukrainian].

Karpenko, O. V., & Kovalenko, S. I. (2005). Sintez 2-R-triazolo[1,5-c]hinazoliniv. Povidomlennia 2 [Synthesis of 2-R-triazolo[1,5-c]quinazolines. Message 2]. Zhurnal orhanichnoi ta pharmatsevtychnoi khimii, 3, 4(12), 61–69. [in Ukrainian].

Karpenko, O. V., & Kovalenko, S. I. (2006). Sintez 2-R-triazolo[1,5-c]hinazoliniv. Povidomlennia 3 [Synthesis of 2-R-triazolo[1,5-c]quinazolines. Message 3]. Zhurnal orhanichnoi ta pharmatsevtychnoi khimii, 4, 2(14), 65–70. [in Ukrainian].

Kovalenko, S. I., Antypenko, L. M., Bilyi, A. K., Kholodnyak, O. V., Antypenko, O. M., Mykhaylova, N. S., et al. (2013). Synthesis and anticancer activity of 2-аlkyl(alkaryl-,aryl-,heteryl-)-[1,2,4]triazolo[1,5-c]quinazolines. SciPharm, 81(2), 359–391. doi: 10.3797/scipharm.1211-08.

Karpenko, O. V., Belenichev, I. F., Kovalenko, S. I., & Sidorova, I. V. (2006). Antyoksydantna ta antyradykalna aktyvnist N`-(khinazolin-4-il)hidrazydiv (get)arylkarbonovykh kyslot i 2-(get)aryl-[1,2,4]triazolo[1,5-c]khinazoliniv [Antioxidant and antiradical activity of N'-(quinazoline-4-yl)hydrazides (get)arylcarboxylic acids and 2-(get)aryl-[1,2,4]triazolo[1,5-c] quinazolines]. Pharmatsevtychnyi zhurnal, 4, 49–54. [in Ukrainian].

Karpenko, O. V., Sidorova, I. V., & Belenichev, I. F. (2005). Doslidzhennia antyoksydantnoi ta antyradykalnoi aktyvnosti 4-(N-akyl)hidrazinohinazoliniv ta ikh kondensovanykh analohiv [Investigation of antioxidant and antiradical activity of 4-(N-acyl)hydrazinoquinazolines and their condensed analogues]. Pharmakom, 4, 61–67. [in Ukrainian].

Martynenko, Yu. V., Kazunin, M. S., Selivanova, E. A., & Kovalenko, S. I. (2016). 2-([1,2,4]triazolo[1,5-c]quinazolin-2-yl-)alkyl-(alkaryl-, aryl-)-amines and their derivatives. Message 1. (3Н-quinazoline-4-yliden)hydrazides (1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)alkyl-(alkaryl-, aryl-)carboxylic acids: features of synthesis, modification and antibacterial activity of synthesized compounds. Zaporozhye medical journal, 4(97), 89–96. doi: 10.14739/2310-1210.2016.4.79709.

Isidro-Llobet, A., Ivarez, M. A., & Albericio, F. (2009). Amino Acid-Protecting Groups. Chem. Rev., 109(6), 2455–2504. doi: 10.1021/cr800323s.

Hudhes, A. B. (2011). Amino acids, peptides and proteins in organic chemistry. Protection reactions, medicinal chemistry, combinatorial synthesis.

Kedare, S. B., & Singh, R. P. (2011). Genesis and development of DPPH method of antioxidant assay. J Food Sci Technol., 48, 412–422. doi: 10.1007/s13197-011-0251-1.

Szabo, M. R., Iditoiu, C., Chambre, D., & Lupea, A. X. (2007). Improved DPPH Determination for Antioxidant Activity Spectrophotometric Assay. Chem. Pap., 61, 214–216. doi: 10.2478/s11696-007-0022-7.

Nakaz Ministerstva okhorony zdorovia Ukrainy «Pro zatverdzhennia metodychnykh vkazivok «Vyznachennia chutlyvosti microorhanismiv do antybacterialnykh preparativ» vid 05.04.2007 roku №167 [Order of the Ministry of Health of Ukraine On approval of guidance Methodological Instructions «Determination of the sensitivity of microorganisms to fntibiotics» from April, 05, 2007 №167]. [in Ukrainian].

Laxmikanth, C., Surenda, B., & Onoka, I. (2016). Thtoretical study of the electronic spectra, static first hyperpolarizability fnd antiradical capacity of 2-pyridone tautomers by density funcional theory (DFT). Anveshana International Journalof Research in Pharmacy and Life Sciences, 1(1).

Ilkevich, N. S., Ribachenko, V. I., Shreder, G., Dmitruk, A. F., & Chotiy, K. Yu. (2010). Izuchenie reactsii gossipola i ego imino-proizvodnih s 2,2-difenyl-1-picrilhydrazilom [Study of the reaction of gossypol and its imino- derivatives with 2,2-diphenyl-1-picrylhydrazyl]. Zhurnal obshchej khimii, 80(2), 276–282. [in Russian].

Kulakov, I. V., Talipov, S. A., Shulga, Z. T., & Seilkhanov, T. M. (2014). Sintez, stroenie i antiradikal'naya aktivnost' novykh proizvodnykh metano[1,3]tiazolo[2,3-d][1,3,5]benzoksadiazokina [Synthesis, structure and antiradical activity of new methano[1,3]thiazolo[2,3-d][1,3,5]benzoxadiazocine derivatives]. Khimiya geterociklicheskikh soedinenij, 10, 1604–1613. [in Russian].

Dautova, I. F., & Khursan, S. L. (2009). Energii dissociacii N-H svyazej 5,6-dizameshchennykh proizvodnykh uracila [The dissociation energy of N-H bonds of 5,6-disubstituted uracil derivatives]. Vestnik Bashkirskogo universiteta, 14(12), 57–63. [in Russian

Downloads

How to Cite

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 2024Nov.2];(3). Available from: http://zmj.zsmu.edu.ua/article/view/130544

Issue

Section

Problems of pharmacy