CC BY
14
№ 8 (122)
август, 2024 г.
CHEMISTRY SCIENCES
BIOORGANIC CHEMISTRY
DOI -10.32743/UniChem.2024.122.8.18019
INDOLE ACETIC ACID DERIVATIVES WITH FUNGICIDE-BASED HETEROCYCLIC COMPOUNDS
Mukhriddin Khudoynazarov
PhD student of Gulistan State University, Uzbekistan, Syrdarya, Gulistan City E-mail: [email protected]
Khabibjon Kushiev
Doctor of biological sciences, professor Scientific Research Institute of Agrobiotechnologies and Biochemistry,
Professor, Gulistan State University, Uzbekistan, Syrdarya, Gulistan City E-mail: [email protected]
Tulkin Djurayev
Scientific Research Institute of Agrobiotechnologies and Biochemistry
Gulistan State University Doctor of Biological Sciences (PhD), Associate Professor.
Uzbekistan, Syrdarya, Gulistan City E-mail: [email protected]
Alisher Djuraev
Senior teacher of Gulistan State University Uzbekistan, Syrdarya, Gulistan City E-mail: [email protected]
Ozoda Ismoiljonova
4th-year bachelor,
Junior researcher of the Scientific Research Institute ofAgrobiotechnologies and Biochemistry
Gulistan State University, Uzbekistan, Syrdarya, Gulistan City E-mail: Ismailjonovaozoda@gmail. com
ПОЛУЧЕНИЕ ПРОИЗВОДНЫХ ИНДОЛУКСУСНОЙ КИСЛОТЫ С ГЕТЕРОЦИКЛИЧЕСКИМИ СОЕДИНЕНИЯМИ, ЯВЛЯЮЩИМИСЯ ОСНОВОЙ ФУНГИЦИДОВ
Худойназаров Мухриддин Шухрат оглы
докторант
Гулистанского государственного университета, Республика Узбекистан, Сырдарьинская область, г. Гулистан
Кушиев Хабибжон Ходжибобоевич
Научно-исследовательский институт агробиотехнологий и биохимии,
доктор биологических наук, профессор Гулистанского государственного университета Республика Узбекистан, Сырдарьинская область, г. Гулистан
Библиографическое описание: INDOLE ACETIC ACID DERIVATIVES WITH FUNGICIDE-BASED HETEROCYCLIC COMPOUNDS // Universum: химия и биология : электрон. научн. журн. Khudoynazarov M.Sh. [и др.]. 2024. 8(122). URL: https://7universum.com/ru/nature/archive/item/18019
№ 8 (122)
август, 2024 г.
Джураев Тулкин Арзикулович
д-р биол. наук (PhD), доцент, Научно-исследовательский институт агробиотехнологий и биохимии Гулистанского государственного университета, Республика Узбекистан, Сырдарьинская Область, г. Гулистан
Джураев Алишер Жаникулович
ст. преподаватель Гулистанского государственного университета, Республика Узбекистан, Сырдарьинская Область, г. Гулистан
Исмаилжонова Озода Бекмурза кызы
4-ый курс бакалавриата, мл. науч. сотр.
Научно-исследовательского института агробиотехнологий и биохимии Гулистанского государственного университета, Республика Узбекистан, Сырдарьинская Область, г. Гулистан
ABSTRACT
Many biologically active compounds have been found among heterocyclic compounds. Such active substances are currently used for various purposes in medicine, agriculture, and the food industry. In particular, substances with a positive effect against bacteria, viruses, and microbes have been found among heterocyclic compounds. Taking into account the high biological activity of Indole 3-acetic acid in our scientific research, 4 different amides with 4-amino antipyrine, 1H-1,2,4-triazole, were synthesised. Thin-layer chromatography of all synthesised substances, Rf values, melting point temperatures, the yield of each reaction (%), and the necessary conditions for the reaction were studied. The obtained new derivatives of indole 3-acetic acid were analyzed based on the results of infrared spectra and HPLC MS.
АННОТАЦИЯ
Среди гетероциклических соединений обнаружены соединения, обладающие большой биологической активностью. Такие активные вещества в настоящее время используются в медицине, сельском хозяйстве, пищевой промышленности для различных целей. В частности, среди гетероциклических соединений были обнаружены вещества с положительным действием против бактерий, вирусов и микробов. В нашем научном исследовании, учитывая высокую биологическую активность индол-3-уксусной кислоты, были синтезированы 4 различных Амида с ее 4-амино-aнтиприном, Ш-1,2,4-триазолом, тонкослойная хроматография всех синтезируемых веществ, значения Rf, температура плавления, выход каждой реакции (%), а также изучены условия прохождения реакции. Новые производные индола 3-уксусной кислоты были проанализированы на основе инфракрасных спектров и результатов ВЭЖХ МС.
Keywords: Indole-3-acetic acid, imidazole, diazole, triazole, dichloro aniline, HPLC-MS, IR-SPIRIT
Ключевые слова: индол-3-уксусная кислота, имидазол, диазол, триазол, дихлор-анилин, ВЭЖХ-МС, ИК-спирит.
Introduction
Phytohormones are low molecular organic compounds produced by plants. Phytohormones are small chemical messenger compounds commonly found in higher plants and microalgae. They are organic substances synthesized from plants, which play an important regulatory role in the entire process of plant life. Plant hormone levels are very low in plants, but they are involved in almost every process that regulates growth and development, including regulation of growth and metabolism and regulation of adaptation to environmental perturbations [1].
Previous studies have shown that auxin (IAA) greatly influences the physiological and biochemical processes of higher plants; exogenous IAA can accelerate fruit development and induce drought tolerance [2].
Many years of research on phytohormones allowed us to identify several substances that make up the group of auxins. Currently, it is known that in addition to ISK, natural auxins include indole-3-butyric acid (IBA) and 4-chloroindole-3-acetic acid (4-Chl-IAA). The molecule
of these substances has an indole ring [3,4].Compared with IAA (indole-3-acetic acid), IBA (indole-3-butyric acid) is more effective in inducing lateral and secondary roots of the plant [5]. In addition, it stimulates the growth of stem elongation much faster [6]. Auxin in the form of 4- Chl-IAA containing an additional chlorine atom is found only in leguminous plants [7].
The synthesis of derivatives of indole-3-acetic acid with high biological activity is connected with the creation of new-generation drugs. Because they show biological activity in small concentrations and amounts.
In this work, an attempt was made to obtain nitrogenous derivatives based on the reaction of Indole-3-acetic acid with imidazoles. The production of these derivatives is related to the creation of drugs with a low level of toxicity against fungal and bacterial diseases and have stimulating properties. This could open up vast new opportunities in agriculture to protect plants from fungal and bacterial diseases and promote growth and development with low toxicity.
There is considerable evidence that reactive oxygen and nitrogen species (ROS and RNS) are involved in several physiological processes, such as host defence against invading pathogens and signal transduction. Overproduction of these reactive species plays a major role in several pathophysiological conditions, including atherosclerosis, cardiovascular disease, Parkinson's and Alzheimer's diseases, and some types of cancer.[8-12] In recent years, the demand for natural and synthetic antioxidants to enhance endogenous protection has increased.
Antioxidants must react with radicals and other reactive species more rapidly than biological substrates to protect biological targets from oxidative damage [13, 14]. In addition, the generated antioxidant radical must be highly stable, meaning that the antioxidant radical must terminate the chain reaction (instead of propagating) Free radical studies provide theoretical information for drug development and provide in vitro methods for rapid drug optimization; It attracts more scientific attention from bioorganic and medicinal chemists. In addition to traditional OH bond type antioxidants, aromatic amines with NH bond function as antioxidants have attracted much attention because aromatic amines are always the central structure of many currently used drugs. Has been. From the literature, phenolic compounds and some aromatic amines (heterocyclic amines) showed antioxidant properties in vitro and were discussed in terms of chemical kinetics [14].
In recent decades, studies on the synthesis and biological properties of indole-3-acetic acid have been
actively conducted all over the world. Although many biological studies have been conducted on indole-3-acetic acid analogues, the antioxidant effect of the same indole-3-acetic acid analogues containing substituted aniline moieties has not been demonstrated [4].
IAA participates in the control of the growth and development of plants by joining auxins. Diazole and triazole are heterocyclic organic compounds with antibacterial and antifungal activity [15].
The experimental part of the work
IAA, diazole, triazole and imidazoles were used in chemical synthesis reaction processes. IAA of 98% purity and diazole, triazole used in the experimental reactions were produced by Sigma-Aldrich (Germany).
HPLC methods with a mass detector, IR and UV were used to make a reliable conclusion about the synthesized compounds.
Preparation of 1H-indole-3-acetyl chloride.
1.75 g (0.01 mol) of indole acetic acid is taken in a 50 ml round bottom flask and dissolved in 30 ml of absolute ether. 5 ml of thionyl chloride is added drop wise while stirring. The reaction was stirred on a magnetic stirrer under reflux for 2 h at 30°C. The progress of the reaction was monitored by TLC using 2:8 methanol: chloroform. Evaporation of the reaction mixture at 60°C gave a concentrated brown solid[15]. The reaction yields 82%. M.p.=115±2°C IR-spirit (Shimadzu) (KBr, cm-1): 2913-3051 (Ar-H), 3410 (NH), 1790 (C=O).
Preparation of 1-amino-(3-imidazol-1-yl propane)-
2-(1H-indol-3-yl)acetamide
1.25g (0.01mol) in a 50ml round-bottom flask
3-propyl imidazole is added and dissolved in 30 ml of absolute tetrahydrofuran. While stirring, 2.1 g (0.01 mol) of 1H-indole-3-acetic chloride is added drop wise. The reaction is heated with stirring at 70-80°C for 30 minutes. 20 ml of cold water is poured into the resulting mixture, a brown substance precipitates, and the substance is filtered and dried at 70-80°C. The dried residue
is recrystallized from ethyl acetate. Partially soluble in ethanol, DMF and well in DMSO. The reaction yield is 86%. M.p.= 180±1°C.
Some physicochemical properties of amides obtained in this way are presented in Table 1.
The synthesis reactions of amides of IAA with several amines 4-amino antipyrine, 3-amino 1,2,4 triazole, and 2,4-dichloroaniline were carried out based on the following scheme.
ChU
Here R=
N
1 N^ 11
H
N-
III
IV
Table 1.
Some physicochemical values of amides
Substances Mr, g/mol M.p °C Brutto's formula Rf Solubility
I 360 180±1 C21H20N4O2 0.47 DMSO, DMF, chloroform, ethyl acetate
II 241 152±1 C12H11N5O 0.46 DMSO, DMF, THF, chloroform, ethyl acetate
III 282 164±1 C16H18N4O2 0.58 DChM, DMF, THF, chloroform, ethyl acetate
IV 319 178±1 C16H12C12N2O 0.61 DMSO, DMF, THF, chloroform, ethyl acetate
System - hexane: ethyl acetate 3:2
4-Amino-(1,5-dimethyl-2-phenylpyrazol-3-one)-2-(1H-indol-3-yl)acetamide.Yield: 62% brown substance, M.p.=180±1, Rf=0.47.IR spectrum (KBr, cm1): 3058-2923 (Ar-H), 3208 (NH), 1647 (C=O), 3363 (NH).
3-Amino-(1H-1,2,4-Triazol)-2-(1H-indol-3-yl)acetamide.Yield: 55% brown-yellow substance, M.p.=152±1, Rf=0.46.IR spectrum (KBr, cm-1): 3057-2856 (Ar-H), 3261 (NH), 1650 (C=O),
1-Amino-N-[2-(2,4-dichlorophenyl)-2-(1H-indol-3-yl)acetamide.Yield: 75% brown-black substance, M.p.=178±1, Rf=0.61.IR spectrum (KBr, cm -1): 30792853 (Ar-H),3254 (NH), 1678 (C=O), 3353 (NH), 1449 (CN), 1503 (Ar(C6H6)), 600 (C-Cl).
Obtained results and their discussion
The IR spectrum of the synthesized amide was studied in comparison with the spectrum of the starting substances. For this, it is necessary to consider the main characteristic vibration areas in the IR spectrum of IAA: at 3380 cm-1 the NH bond in the indole molecule, and at 1685 cm-1 the valence vibrations related to its carbonyl part are observed. In addition, the wave numbers
corresponding to the OH functional group of the IAA molecule appear at 2730 to 3127 cm-1[Figure 1].
The following vibrational frequencies were observed in the IR spectrum of 3-amino propyl imidazole amide of IAA: wave numbers indicating the NH group of the starting substance IAA at 3380 cm-1 and the band belonging to the amino group at 3360 and 3290 cm-1 in 3-amino propyl imidazole wavenumbers were available. In the IR spectrum of the product, 3360 cm-1 was not visible, from which it can be concluded that an amide bond was formed. It can also be concluded from the IR spectrum that the product obtained by shifting the wave number of 1685 cm-1 to 1635 cm-1 (40 cm-1) is also present in the IR spectrum. NH in the indole molecule initially gave an absorption at 3380 cm-1 but shifted 27 cm-1 forward in the product to give an absorption at 3407 cm-1. It can be concluded that the absorption at 3407 cm-1 belongs to the NH functional group in the indole ring, and the absorptions at 3245 cm-1 belong to the amino group in the 3-amino propyl imidazole molecule[Figure 1].
100
80
60
40
20
4000
3600
3200 IAA
2800 2400 -IAA ChlA
2000 1600 1200 800 IAA 3-amino propyl imidazole amide
400
Figure 1. IR spectra of Indole-3-acetic acid, Indole-3-acetic acid chloride and Indole-3-acetic acid 3-amino propyl
imidazole amide
At the next stage of our work, the chemical structure and purity of IAA amide (3-amino propyl imidazole 1H-indole-3-acetic acid amide) were investigated using the mass spectrometry method. The presence of a molecular
ion ([M+] 283.15 m/z.) (Fig. 2) and its correspondence with the theoretically calculated molecular ion indicate the synthesized compound 1-amino-(3-imidazol-1-yl propane)-2-(indicates that it is 1H-indol-3-yl)acetamide.
xlO B 4.25
+ESI Scan (0.160 min) Frafl=175.0V M01800028.d
100 125 150 175 200 225 250 275
350 375 400 425 450 475 500 525 550 575 600 625 Counts vs. Mass-to-cnaige (m/z)
675 700 725 750 775
875 900 925 950 975 1000
Figure 2. 1-amino-(3-imidazol-1-yl propane)-2-(1H-indol-3-yl) acetamide(m/z)=283
0
Conclusion
4 types of indole acetic acid amides were synthesized. Their physical properties were studied. Infra-red spectra, Ultraviolet and HPLC-MS analyzes of the obtained amides were carried out.
Carbonyl (C=O) in indole acetic acid 1685 cm-1 wave number shifted to 1635 cm-1 state (40 cm-1) and the obtained product was also present in the IR-spectrum. NH in the indole molecule initially gave an absorption at 3380 cm-1 but shifted 27 cm-1 forward in the product to give an absorption at 3407 cm-1. It can be concluded that the absorption at 3407 cm-1 belongs to the NH functional group in the indole ring, and the absorptions
at 3245 cm-1 belong to the amino group in the 3-amino propyl imidazole molecule.
The chemical structure and purity of 1-amino-(3-imidazol-1-yl propane)-2-(1H-indol-3-yl)acetamide were investigated using the mass spectrometry method. The presence of a molecular ion ([M+] 283.15 m/z.) and its correspondence with the theoretically calculated molecular ion indicate the synthesized compound 1-amino-(3-imidazol-1-yl propane)-2-(1H-indol-3 indicates that it is -yl)acetamide.
Such compounds may exhibit various biological activities. The effect of obtained heterocyclic amides on plants and fungi is being studied.
References:
1. Wob U., Bishopp A., Farcot E., Bennett MJ. // Modeling of hormonal response and development. Trends Plant Sci. 2014; 19 :311—319
2. Rotino GL, Perri E, Zottini M, Sommer H, Spena A: // Genetic engineering of parthenocarpic plants. Nature Biotechnol 15: 1398-1401
3. Morris, D.A.; Frimal, J.; Zazímalová, E. // The transport of auxins. In Plant Hormones: Biosynthesis, Signal Transduction, Action; Davies, P.J., Ed.; Kluwer Academic Publishers: Dordrecht, The Netherlands, 2004; pp. 437-470.
4. Márquez, G.; Alarcón, M.V.; Salguero, J. //Differential responses of primary and lateral roots to indole-3-acetic acid, indole-3-butyric acid, and 1-naphthaleneacetic acid in maize seedlings. Biol. Plant 2016,60, 367-375.
5. Bartel, B.; LeClere, S.; Magidion, M.; Zolman, B.K. // Inputs to the active indole-acetic acid pool: De novo synthesis, conjugate hydrolysis and indole-3-butyric acid P-oxidation. J. Plant Growth Regul.2001,20, 198-216.
6. Woodward, A.W.; Bartel, B. // Auxin: Regulation, action, and interaction. Ann. Bot. 2005, 95, 707-735.
7. Jakubowska, A.; Zielinska, E.; Kowalczyk, S. // Metabolism and transport of auxin in plants. Post. Bioch. 2001, 47, 169-182.
8. Gibson, G.E. //Interactions of oxidative stress with cellular calcium dynamics and glucose metabolism in Alzheimer's disease Free Radical Biol. Med.2002,32, 1061-1070.
9. Giasson, B.I.; Ischiropoulos, H.;Lee, V.M.Y.;Trojanowski, J.Q. //The relationship between oxidative/nitrative stress and pathological inclusions in Alzheimer's and Parkinson's diseases Free Radical Biol. Med. 2002,32, 1264-1275.
10. Heinecke, J.W. //Oxidized amino acids: culprits in human atherosclerosis and indicators of oxidative stress Free. Radic. Biol. Med.2002,32, 1090-1101.
11. Hazell, L.J.; Baernthaler, G.; Stocker, R. //Correlation between intima-to-media ratio, apolipoprotein B-100, myeloperoxidase, and hypochlorite-oxidized proteins in human atherosclerosis Free Radical Biol. Med. 2001, 31, 1254-1262.
12. Cuzzocrea, S.; Riley, D.P.; Caputi, A.P.; Salvemini, D. //Antioxidant therapy: A new pharmacological approach in shock, inflammation, and ischemia/reperfusion injury.Pharm. Rev.2001, 53, 135-159.
13. You-Zhi, T.; Zai-Qun, L. //Free-radical-scavenging effect of carbazole derivatives on AAPH-induced hemolysis of human erythrocytes Bioorg. Med. Chem. 2007, 15, 1903-1913.
14. Salopek-sondi, B.; Piljac-Zegarac, J.; Magnus, V.; Kopjar, N.J. // Free radical-scavenging activity and DNA damaging potential of auxins IAA and 2-methyl-IAA evaluated in human neutrophils by the alkaline comet assay Biochem. Mole Toxi. 2010, 24, 165-173.
15. Nagaraja Naik, Honnaiah Vijay Kumar and Salakatte Thammaiah Harini // Synthesis and antioxidant evaluation of novel indole-3-acetic acid analogues European Journal of Chemistry September 2011 DOI: 10.5155/eurjchem.2.3.337-341.363.
