CC BY
0
272
CHEMICAL PROBLEMS 2025 no. 2 (23) ISSN 2221-8688
PREPARATION, IDENTIFICATION AND STUDY THE BIOLOGICAL ACTIVITY OF NOVEL HETEROCYCLIC COMPOUNDS DERIVED FROM AZO-CHALCONE
Ruwa M. Mauf Neam H. Saleem2
1 Department of Chemistry, College of Education for Girls, University ofMosul, Mosul, Iraq.
2Department of Chemistry, College of Education for Pure Science, University of Mosul, Mosul, Iraq.
*e-mail: [email protected]
Received 14.06.2024 Accepted 05.08.2024
Abstract: This work describes the preparation and spectroscopic investigation of new heterocyclic compounds derived from the 4-aminoantipyrene moiety. The compound (R1)3-((1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)diaz-enyl)-4-hydroxybenzaldehyde was prepared by reacting 4-aminoantipyrene with 4-Hydroxybenzaldehyde according to the cold condition at (0-5) Celsius. This represents the starting point to create novel azo-chalcone compounds with a new nucleus as the alpha-beta unsaturated group, and the formation of compound (R2-6) via acetophenone derivatives using ethanol as a solvent under a basic medium, and for synthesis of various compounds of 4-((5-((Z)-3-argio-3-oxoprop-1-en-1-yl)-2-hydroxyphenyl)diazenyl)-1,5-dimethyl-2-phenyl-1,2-dihydro-3H-pyrazol-3-one, using the cyclization of these compounds via (urea and hydrazine hydrate) to forming five and six novel heterocyclic rings of 4-((5-(2-amino)-4-Argyo-6H-1,3-oxazine-6-yl)-2-hydroxyphenyl(diazenyl)-1,5-dimethyl-2-phenyl-1,2-dihydro-3H-pyrazole-3-one [R7, 11], and 4-((5-(5-(4-argiophenyl)-4,5-dihydro-1H-pyrazol-4-yl)-2-hydroxyphenyl)diazenyl)-1,5-dimethyl-2-phenyl-1,2-dihydro-3H-pyrazole-3-one [Rn.16], respectively. Some diagnostic measurements have been used to characterize these molecules, such as melting point, thin-layer chromatography, measuring Nuclear Magnetic Resonance, Spectroscopy in the Infrared, and Mass Spectrometry, and determining the effectiveness of some of these compounds by diagnosing their effectiveness against types of pathogenic bacteria.
Keywords: Chalcone, Azo-Chalcone, 4-Amino Antipyrene, Biological Activity DOI: 10.32737/2221-8688-2025-2-272-285
1. Introduction
Chalcone is one of the carbonyl compounds and among the most widespread organic compounds in biological and organic chemistry [1, 2] and it is a source for building important compounds in the industrial and medical fields [3]. a-P unsaturated compounds contain a carbonyl group that exists in a replaced state with an unsaturated group (C=C) [4]. The double bond (C-C) and the bond (COO) are separated by a single bond [5], and the two bonds are in an alternating state. The coupling between the two groups represents the possibility of spreading charges across the four atoms, which gives stability to the chain system due to the presence of resonance [6].
Because of the presence of the keto ethylenic moiety, CO-CH=CH-, chalcones and their derivatives are regarded valuable. Moieties
in the domain of synthetic and heterocyclic organic chemistry [7] were created via Claisen-Schmidt synthesis [8] by condensation acetophenones together with benzaldehyde substitutes [9].
Chalcones consider a-P unsaturated compounds that dissolve in organic solvents but not in water. Kastanek first used chalcone terminology in 1899, when he conducted preliminary experiments in preparing natural colored compounds [10]. Chalcone is a basic chemical scaffold found in many plant products such as fruits, tea, and vegetables [8]. Chalcone has an extrinsic spectrum of biological activity [11] and occupies an important place in biochemistry and medicine because it is antiinflammatory [12, 13]. It is antibacterial, antiviral [14], anti-tuberculous [15], antitumor
CHEMICAL PROBLEMS 2025 no. 2 (23)
www .chemprob.org
[16, 17], anti-HIV [18], anti-fungal, antioxidant [19] and anti-ulcer agents [20].
Azo-chalcone dyes, common in vegetables, plants, and fruits, are compounds with systems linked to heterocyclic or
degradable aromatic rings [21]. These a major source for the synthesis of new organic compounds, such as heterocyclic compounds, which may have promising biological activity [22].
2. Experimental part
2.1. Material and methods.
The Smp.30 device, produced by the British company STURART, was employed to measure melting temperatures to the prepared compounds. The chemicals used were purchased from BHD and Fluka and Sigma Aldrich. The infrared spectra were measured using IR Affinity-S 1, a Shimadzu type device at a wavenumber of (4000-600 cm-1).
1H-NMR using America Bruker 400MHz, TMS was used internal standard; DMSO-d6 was used as the solvent. The mass spectrums were also observed via (GCMS-QP 2010 plus), Japanese origin, a Shimadzu type device. The reaction was followed using thin -layer chromatography (TLC) was carried out in silica gel (120 mash) coated plates (1*10). The media for microorganisms was sterilized using an autoclave device equipped from a Spanish company, the dishes were developed in an incubator device, and testing was done in the laboratories of the Microbiology Division in the College of Science.
2.2. General procedure for synthesis of 3-((1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)diazenyl)-4-
hydroxybenzaldehyde (R1) [23].
A (0.01 mol, 2.03 g) of 4-amino antipyrin was dissolved in mixture of 7 ml concentrated hydrochloric acid (37%) with (7 ml) of (H2O) in an ice bath while constant stirring until the temperature reacted (0-5 °C). In another bowl, 1.6 g of sodium nitrite was dissolved in 8 ml H2O. The sodium nitrate solution was added in batches to the first solution with continuous stirring (1-2ml) for each batch. In this case, it is necessary to maintain the temperature of the ice bath so that the temperature does not rise above 5 °C. The solution formed diazonium salt in the ice bath solution- was prepared (0.1g) from 4-hydroxy benzaldehyde and dissolved it in 2 ml of diluted (10% NaOH) by adding 5 ml of H2O. The last solution was stirred and then added to 2 ml of diazonium salt.
Observing the formation of dye, the solution leaves for 15 min in an ice bath to settle. The crystals of the dye thickly separated, filtered and recrystallized with ethanol: water at ratio 1:2 orang needle crystals separated at melting point (168-169 °C), (monitored via TLC). The solvent system (4:1) benzene:MeOH. RF was 6.5.
4-aminoantipyrin
2.3. Preparation of 4-((5-((Z)-3-argio-3-oxoprop-1-en-1-yl)-2-hydroxyphenyl)-diazenyl)-1,5-dimethyl-2-phenyl-1,2-dihydro-3H-pyrazol-3-one (R2-6) [24]
In a 100 ml round-bottomed flask (0.004 mol) of the aldehyde derivative (R1) was placed and 10 ml of ethanol with (0.004 mol) of acetophenone derivatives dissolved in 10 ml of ethanol were added to it. The reaction mixture
(R1)
was stirred with a magnetic stirrer for 2 hours and the reaction was noted (TLC), the solvent system was benzene:methanol (4:1). After heating was completed, the mixture was cooled and 15 ml of chilled water was poured in. Then it was filtered and recrystallized with ethanol. The azo-chalcone compound (R2-6) was recognized. The physical data of these compounds are listed in Table 1.
(Ri) (R2-6)
Table 1. Physical data of compounds (R2-6)
Co mp No. Ar Molecular formula and m.wt g/mol M.P. (°C) Yield % Rf Colour
R2 C25H19N5O5 469 222223 85 0.6 25 Brown powder
R3 n02 <> C25H19N5O5 469 178180 82 0.5 42 Brown powder
R4 C25H19N4O3CL 458 -229 228 73.5 0.4 3 Brown powder
R5 ci,_^ C25H19N4O3CL 458 -110 108 74 0.6 6 White powder
R6 -K> C26H22N4O3CL 473 -228 227 90 0.7 1 White powder
2.4. Preparation of 4-((5-(2-amino-4-argio-6H-1,3-oxazin-6-yl)-2-hydroxy-phenyl)diazenyl)-1,5-dimethyl-2-phenyl-1,2-dihydro-3H-pyrazol-3-one(R7-11) [25].
A mixture of 0.02 mol of chalcone derivatives (R2-6) with (0.02 mol, 1.2 g) of urea in (10%) NaOH was dissolved, the mixture was stirred with a magnetic stirrer for (3-4 hours), 20
ml of cold water was poured into the reaction mixture and stirring was continued for another hour. Then the reaction mixture was left in the refrigerator for (24 hours). Then drops of hydrochloric acid were added to the equation, the resulting precipitate was filtered and recrystallized from methanol. Physical data of compounds (R7-11) are given in Table 2.
(R2-6) (R7-11)
Table 2. Physical data of compound ^ (R7-11)
Comp. No Ar Molecular formula and m.wt, g/mol M.P. (°C) Yield % Rf Colour
R7 C26H22N5O5 512 180182 81 0.45 Orange powder
R8 no2 -K3 C26H22N5O5 512 72-73 85 0.55 White powder
R9 C26H22N6O3CL 501 -164 163 75 0.6 Yellow powder
R10 ci,_v -0 C26H22N6O3CL 501 86-88 88 0.44 Yellow powder
R11 40 C27H25N6O3 481 212213 90 0.62 White powder
2.5. Preparation of 4-((5-(3-argio-1H-pyrazol-5-yl)-2-hydroxyphenyl)diazenyl)-1,5-dimethyl-2-phenyl-1,2-dihydro-3H-pyrazol-3-one (R12-16) [26] .
In a solution prepared from (0.0015 mole) chalcone derivatives (R2-6) dissolved in 30 ml absolute ethanol and added (0.0015 mol, 0.048 g) hydrazine hydrate with few drops from
2.6. Mass spectra study [27]
(0.01) g of the sample was dissolved in (5 ml) of ethanol, the device injector was set (2) microliters of sample by using a capillary column of the type (inert cap 1) is a non-polar column bonded 100% dimethylpoly siloxane (DMSO) with a length (30) meters, the carrier gas was helium at a flow rate of (30 ml / min).
At 50°, the oven temperature program was initiated with split ratio of 1:2, this temperature was continued for 2 minutes, after which the temperature was raised at a rate of 25°C per minute until reaching a temperature of 200°C, and then held for 1 minute with a total holding
glacial acetic acid, the reaction of mixture was refluxed for (15 hour), the resultant precipitate is filtered and washed by water then recrystallized via ethanol monitored by (TLC) the solvent system 4:1 benzen:MeOH. Physical properties of compounds (R12-16) are listed in Table 3.
time of 7 minute. The mass spectra were recorded with a range of m / z 900 -30 with an energy of 27 ev.
2.7. The Biological study [28, 29]
Preparation of the agar-Mueller-Hinton medium used in bacterial growth: agar-weld fusion method was used action biological effectiveness of some synthesized chemical compounds (Ri, R2, R5, R8, R9, R14, R16) , where (38g) molar "Hinton Agar" was dissolved via distilled boiled water, the acid function of a culture medium was neutralized to (pH = 7). The resulting solution was placed in an autoclave under pressure (150 Pounds/inj) at
(R2-6) (R12-16)
Table (3) Physical data of compound (R12-16)
Comp No. Ar Molecular formula and m.wt; g/mol M.P(0 c) Yield % Rf Colour
R12 C26H22N6O4S 512 220221 72 0.6 3 Yellow powder
R13 no2 C26H22N5O5S 512 76-77 74.5 0.6 5 Wight powder
R14 ü- C26H22N6O3SC L 501 -167 165 65 0.4 5 Yellow powder
R15 ci._, -0 C26H22N6O3SC L 501 96-97 55 0.3 5 Brawn powder
R16 C27H25N6O3S 481 175177 80 0.6 2 White powder
(121°C) after the temperature decreased to about (50°C), then the resulting solution was poured into a glass dish with a thickness of (10.5 cm) for each. After that, the solution is left in the incubator for 24 hours until it solidifies.
Preparation of selected compounds. These compounds (R1, R2, R5, Rs, R9, R14, R16) are prepared by dissolving them using a solvent other than water, which is dimethyl sulfoxide, at a concentration of 200 mg/1ml and 500 mg/1ml.
The bacterial isolates used. In the
current research, four kinds of bacteria were identified: Gram-positive bacteria called Staphylococcus aurous and Gram-negative bacteria (Proteus mirabilis, Ecoli, Morganella morgani) and the uses of these types in applying the effectiveness through the metric cylinder method with a cork borer. The process of making holes and spreading certain bacteria on the surface of the dish was performed using sterile cotton. Leave the dishes at a temperature of (37) for (20 minutes) dishes are inserted at (372) for (20min).
3. Result and discussion
The research included the preparation of azo-chalcone derivatives by reacting the Diaz onium salt with 4-hydroxybenzaldehyde to form the aromatic aldehyde derivative, which reacts via Claisen-Schmidt condensation with
acetophenone derivatives. The other step involved cyclizing the azo-chalcone derivatives with cyclizing agents such as urea and hydrazine [30] according to the Scheme 1.
NnN02/HCL
(0-5)C
10%NaOH
ho
■i
J HO
Ar-CCHj
4-((3-((>f)-3 -arglo-3-oxoprop-l -en-1 -yl)-f»-hy droxy cyclohexa-1,5-dIen-l-yl)diazenyl)-l,S-dimethyl-2-phenyl-1,2-dihydro-3//-pyrazol-3-one (R^g)
NH2NH2.
H.
.Ar
Or
-yiJ HO_
rs>N=NHq,
öO /-h2n
Ar
-NH (R 12-16)
4((2hydroxy5^5raethyl4,5dihydrol//pyrazoi4yl)phenyl)dlazcnyl)l,5dInicthyl2phenyl
1 ,2-diIi.y dro-3/Z-pyr azol-3-one compound with argon (1:1) 4-((5-<2-»inJno-4-argio-Äff-l,3-oxaziii-6-
yl)-2-hydroxyphenyl)diazenyl)-l,5-dimethyl-2-p henyl-1 ¿2-diliydro-3/r-N02 m pyrazol-3-one
Ar: -Q-NOi ■ -Qci • -€>'
ch.
Scheme 1. Synthesis of compounds (R1-16)
The aromatic aldehyde derivatives (Ri) for the N=N azo group and aldehyde carbonyl was identified by FTIR, where it gave,1436 cm-1 group an absorption band appeared at 1681 cm-
1, an absorption band for OH- group of phenol appeared a peak 3236 cm-1 for aldehyde stretch [31] (Fig. 1). However, the H1-NMR spectra for (R1) compounds as shown up: 2.44ppm(s,CH3,3H at CH3) 3.15ppm(s,CHs,3H-
As for the compounds (R 2-6), their infrared spectrum showed a clear band at (15091421) cm-1 for N=N azo-group, and carbonyl
N-CH3), 7.35 ppm (s,1H,phenyl ring), 7.37ppm (m,5H,for phenyl ring), 7.71ppm(d.2H.phenyl ring),9.44ppm(s,1H,C=O).9.82ppm(s,1H.OH phenol), as displayed in Fig. 2.
group at (1689-1618) cm-1. C-H aromatic at (3050-3010) cm-1 and strong bands related at C=C Alkene at (1608-1601) cm-1.
Fig. 2. 1H-NMR spectra of (Ri)
Table 4. FTIR spectra of compounds (R2-6)
Comp No Ar IR.KBr, v( cm-1)
N=N C=C OH C-H aromatic C=O C==C Others
R2 tO"^ 1452 1608 3048 1654 14131579 N-O 1308 Sym 1509 Assy
R3 no2 -K3 1421 1601 3580 3012 1689 14211577 N-O 1136 Sym 1499Assy
R4 0 1509 1601 3580 3010 1650 14551576 C-Cl 746
R5 ci_ 1449 1601 3567 3050 1677 14211576 C-Cl 700
R6 i-OcH3 1454 1605 3582 3049 1618 14161579
Table 5. The 1H-NMR spectra data were indicated
Comp. No R 1H-NMR (ppm) DMSA-d6
R2 "KD"^ 2.42 (5,3H, for CH3), 3.14 (S, 3H, for N-CH3) 6.82- 6.85 (m, CH, 1H for aromatic ring), 7.38-7.52( m, CH,1H for aromatic ring), 7.67-(d, CH,2H for methylene group), 9.95 (S, 1H,OH - phenol).
r5 ci,_, 0 2.43(s,3H, for CH3),3.13 ( s, 3H, for N-CHa),6.8 (s,1H,1H for 1-ethylene),7.31-7.75( m,9H,1H for aromatic ring),9.44 (s, 1H, OH-phenol).
Then, all spectroscopic information about respectively, and Fig. 3 and 4. FTIR and 1H-NMR as shown in Tables 4 and 5,
Fig. 3. 1H-NMR spectra of (R2)
Fig. 4. 1H-NMR spectra of (R5)
w- 11J
Comp. No Ar IRN cm-1
N=N C=C C=N C-H NH2 Others
R7 1436 1611 1596 3033 3209 N-O 1341 Sym 1491 Assy.
R8 no, <5 1429 1602 1576 3088 3256 N-O 1335 Sym 1470 Assy.
R9 1458 1616 1597 3033 3216 C-Cl 746
Rl0 CI,_, -O 1456 1595 1576 2163 3566 C-Cl 763
Rl1 1457 1602 1577 -- 3546
Urea was used to convert chalcone group in compound (R2-6) to 1,3-oxazine compounds (R7-11) in 10% NaOH via cyclization chalcone group with stir the mixture magnetically for 3-4 hours. These compounds were characterized by FTIR and showed the following main
absorption bands (1429 -1458) cm-1 for N=N, (2163-3088) cm-1 for C=C, and Clear bands appear for the amine group (NH2) at (32093566) cm-1. All spectroscopic information is shown in Tables 6 and 7.
rable 7. The 'H-NMR spectra data.
Comp. No R H1-NMR(PPM)-DMSO-d6
R11 2.51ppm (s, 3H, forCHs), 3.13 (S,3H, for N-CH3), 6.83 (S, 2H , 2H for NH2), 6.86-7.67 (m,8H , CH for benzene ring), 9.47 (S, ,1H ,OH- phenol)
Fig. 5. 1H-NMR spectra to sample (R11)
>-12-16
Comp No Ar N=N C=C C-H Aliphatic C=N N-H Other
R12 1456 1591 2617 1631 3400 N-O 1373 Sym 1456 Assy
R13 no2 1514 1598 2858 1643 3325 N-O 1377 Sym 1475 Assy
R14 1454 1577 2922 1602 3398 C-Cl/750
R15 -Kw> 1444 1593 2400 1593 3375 C-Cl/750
R16 1498 1579 2953 1600 3325
Hydrazine hydrate was used to convert chalcone group in compounds (R2-6) to pyrazole compounds (R12-16) in absolute ethanol and
reflexed the mixture for (15 hour) with few drops Glacial acetic acid. These compounds characterized by FTIR and showed the
following main absorption bands (1444-1556) for C=N, and (3325-3400) cm-1 for N-H. All cm"1 for N=N, (1577-1598) for C=C, (2400- spectroscopic data appeared in Tables 8 and 9. 2617) cm-1 for C-H Aliphatic, (1593-1643) cm-1
Table 9. The 'H-NMR spectra data were indicated
Comp No R H1-NMR (ppm)-DMSO-d6
R13 no2 -K3 2.07 (s,3H , for CH3), 3.86 (s, 3H for N-CH3), 6.80 -7.63 (m, 11H, CH for aromatic ring), 8.07 (s,NH,1H for pyrazole ring), 8.41 (s,1H,OH - phenol).
R16 2.43(s,3H , for CH3),3.17 s, 3H for N-CH3),6.83(s,1H,CH for pyrazole ring),7.19-7.46(m,12H,CH for aromatic ring),9.8(s,1H,OH for phenol
Fig. 6. 'H-NMR spectra to sample (R13)
Fig. 7. GCMS of (Ri)
Results of mass spectrometry study:
Using mass spectrometry is considered an important analytical tool [32] as a measure the mass-to-charge ratio involving one or more molecules present in the sample. The use of
mass spectrometry to calculate the exact molecular weight and identify unknown compounds by determining their molecular weight, and for the purpose of proving the structural formula [33] of the prepared
compounds, the compounds (Ri, R4, R5, R10) were chosen and a gas-mass chromatography was measured for them, where the fractionation showed their exact molecular weights, which are equal to the molecular weights calculated theoretically. Where the compound (R1) gave the mass/charge ratio (M/Z) at (336) with a main fragmentation bund base peak (60) and the compound (R13) gave (M/Z)=(495) with a base peak (45) at abundance 100%, the compound (R6) also gave the mass ratio (M/Z)
at (452) with a base peak at (107) abandunce 100%, while the compound (Rs) gave a ratio (M/Z) at (524) a main or base peak at (44). So, these ratios are considered identical to the molecular weights calculated theoretically, in addition to the other broken units whose masses are listed in Table 10, and the spectral shapes (Fig. 7, 8, and 9) they describe the mass spectrometry of the compounds (Ri) (R13) and (R6), respectively.
Fig. 8. GCMS of (R13)
Fig. 9. GCMS of (R6)
Comp. No Structure m/z value Base peak
Some of the breakdowns of compounds can be following Scheme 2: example the compound interpreted hypothetically and as in the (R6).
Ri j ho ûNT=N^o 336 60
R13 h 495 45
R6 a \ h —' 452 107
R8 n02 (J 0 nh2 524 44
H3CHN-
1
-NH
Ph'
N Ph'
/ H
HO.
O
II /=\
M
CH3
H2C-
II /=\
CH3
m/z=122(70%) m/z—205(30%) m/z=107(100%) m/z=133(46%)
M.W-452 (22%) for total compound
Scheme 2. Proposed fragmentation pattern of compound (R6)
Antimicrobial activity outcome:
The bacterial activity of some laboratory-prepared compounds (Ri, R2, R5, Rs, R9, R14, Ri6) was evaluated Each compound is prepared against one type of bacteria isolated and identified, namely gram-Negative bacteria, there are three types howeve isolated Including (Proteus Mirabili, Morganella Morgani, Ecoli) and staphylococcus aurousis gram positive bacteria The tested compounds showed high inactivation activity, and some of them were moderate, at a concentration of 500 mg/1ml, while the 200 mg/1ml concentration of the
prepared compounds did not give any significant activity. Note that a pilot study was conducted at concentrations less than 200 mg/1ml as mentioned in the literature, and it did not give any significant effectiveness.
The highest effectiveness was observed for the two compounds (R14, Ri6), as they gave an inhibition diameter of (35) (31) and respectively with Morganella Morgani bacteria and the diameter of inhibition (30) with E.coli and the Table 11 shows the sensitivity of the bacteria to some of the prepared compound and Fig. 10 below illustrate this.
Table ^ 11. Activity results for the compounds against Bacteria
Comp. No The symbol of the compound on the plate Inhibitory Zone (mm) at cosentration 200 mg/1ml Inhibitory Zone (mm)at concentration 500 mg/1ml
Staph aureu E.coli Morganella Mirabilis Proteus Mirabilis
Ri 1
R2 6 20
R5 5 22 15 15 20
R8 10 28
R9 9
R14 7 30 30 35
R16 8 25 30 31
Fig. 10. The anti-bacterial activity of prepared compounds 4. Conclusion
New azo-chalcone derivatives were prepared as heterocyclic compounds and investigated by several important spectroscopic measurements. The biological activity of some of them was also studied, and compounds with high inhibitory activity or strong inhibition were identified. For example, two compounds (R14, Ri6) showed good results against two types of bacteria Morganella Morgani bacteria and E.coli, respectively, which cause diseases in humans. In light of the phenomenon of bacterial resistance to many antibiotics, these compounds can be considered as alternatives for treatment if they are combined with antibiotics to increase
their effectiveness; especially when binding to these compounds, synergy can occur between them and achieve good results. The importance of the research is the use of synthetic or semi-synthetic alternative drugs, since they are used to treat infections caused by these bacteria, such as urinary tract infections, wound infections and burns. Therefore, we recommend that histological and anatomical studies be carried out on the prepared compounds so that they can be used as promising alternatives. We recommend further study of azo-chalcone compounds and preparation of other new lines of them.
References
1. Sekar P., Kumar Sh., Raju S.K. Chemistry and synthetic methodologies of chalcones and their derivatives: A review. International Journal of Biological and Pharmaceutical Sciences Archive, 2023, Vol. 05(01), pp. 51-
072. doi.org/10.53771/ijbpsa.2023.5.1.0020 2. Wilhelm A., Bonnet S.L., Twigge L., Rarova L., Stenclova T., Visser H.G., Schutte-Smith M. Synthesis, characterization and cytotoxic evaluation of chalcone derivatives. J. Mol.
Struct. 2022, Vol. 1251, 132001. doi:10.1016/j.molstruc.2021.132001.
3. Al-Tufah MM. Synthesis and characterization of some new cyclohexenone compounds derived from chalconescc and evaluation of bacterial activity. College of Basic Education Researchers Journal, 2022, Vol. 18(4), p. 748-806.
4. Nguyen T.T., Phan N.T.S., Tran C.T.H., Tran Q.D., Ly D., Nguyen T.T., Nguyen K.X. A one-pot synthesis of disubstituted thiazoles from chalcone C-H bonds, elemental sulfur, and Glycine ethyl ester. Synlett. 2022, Vol. (33), p. 555-558. doi:10.1055/s0041-17378.
5. Hussein M.S., Khalaf M M. Synthesis bis-chalcones, pyrazoline ring and evaluation microbial activity for some of them. Samarra J. Pure Appl. Sci, 2022, Vol. 4(3), p. 46-60.
6. Caray F A. "Organic Chemistry" 4th Ed., Mc Graw-Hill Higher Education, 2000 pp. 861.
7. Mukhtara Sh.S., Morsya N.M., Hassana A.S., Hafeza T.S., Hassaneen H.M., Saleh F.M. A Review of Chalcones, Synthesis, Reactions, and Biological Importance. Egypt. J. Chem. 2022, Vol. 65(8), p. 379 - 395.
8. Rammohan A., Reddy J.S., Sravya G., Rao Ch.N., Zyryanov G.V. Chalcone synthesis, properties and medicinal applications: a review. Environmental Chemistry Letters. 2020, p. 1-38 doi.org/10.1007/s10311-019-00959-w.
9. Vidja H., Shiyaliya B., Patel J., Nagar A. Synthesis of chalcones. Journal of Emerging Technologies and Innovative Research (JETIR), 2020, Vol. 7(7), p. 915-923
10. Carey F. "Introduction to Organic Chemistry" Ed., Streitwieses Heath Co Ck and Kosower, Colorado 2007, p. 794-799.
11. Obaid S.S., Abd Allatif N.A.A. Biological activity of new heterocyclic compounds derived from chalcone. Eurasian Chem. Commun. 2023, Vol. 5, p. 712-719. doi.org/10.22034/ecc.2023.390874.1611.
12. Ngameni B., Cedric K., Mbaveng A.T., Erdogan M., Simo I., Kuete V., Dastan A. Design, synthesis, characterization, and anticancer activity of a novel series of O-substituted chalcone derivatives. Bioorganic & Medicinal Chemistry Letters. 2021, Vol. 35, p. 2-7. doi.org/10.1016/j.bmcl.2021.127827 .
13. Emam S.H., Sonousi A., Osman E.O., Hwang D., Kim G.D., Hassan R.A. Design and synthesis of methoxyphenyl- and coumarin-based chalcone derivatives as anti-inflammatory agents by inhibition of NO production and down-regulation of NF-kB in LPS-induced RAW264.7 macrophage cells. Bioorg Chem. 2021, Vol. 107, 104630. doi: 10.1016/j .bioorg.2021.104630.
14. Baper Sh.H., Mohammed M.S. Preparation and characterization of new azo-chalcone mixed with imidazole ligand coordinated with some chelate complexes and study antitumor activity. HIV Nursing. 2022, Vol. 22(2), p. 318-326.
15. Thapa P., Upadhyay S.P., Suo W.Z., Singh V., Gurung P., Lee E.S., Sharma R., Sharma M. Chalcone and its analogs: Therapeutic and diagnostic applications in Alzheimer's disease. Bioorg. Chem. 2021, Vol. 108, p. 104681. doi: 10.1016/j .bioorg.2021.10468125.
16. Ouyang Y., Li J., Chen X., Fu X., Sun S., Wu Q. Chalcone derivatives: Role in anticancer therapy. Biomolecules. 2021, Vol. 11, p. 894. doi:10.3390/biom11060894.
17. Salehi B., Quispe C., Chamkhi I., El Omari N., Balahbib A., Sharifi-Rad J., Bouyahya A., Akram M., Iqbal M., Docea A.O., Caruntu C., Leyva-Gómez G., Dey A., Martorell M., Calina D., López V., Les F., Pharmacological properties of chalcones: A review of preclinical including molecular mechanisms and clinicalevidence. Front.Pharmacol. 2021, Vol. 11, p. 592654. doi:10.3389/fphar.2020.592654.
18. Sharma H., Patil Sh., Sanchez T.W., Neamati N., Schinazi R.F., Buolamwini J.K. Synthesis, biological evaluation and 3D-QSAR studies of 3-keto salicylic acid chalcones and related amides as novel HIV-1 integrase inhibitors. Bioorganic & Medicinal Chemistry, 2011, Vol. 19, p. 2030-2045. doi.org/10.1016/i.bmc.2011.01.047.
19. Elkanz N.A.A., Hrichi H., Alolayan R.A., Derafa W., Zahou Fatin M., Bakr R.B. Synthesis of Chalcones Derivatives and Their Biological Activities, A Review. ACS
Omega. 2022, Vol. 32(7), p. 27769-27786. doi.org/10.1021/acsomega.2c01779.
20. Marotta L., Rossi S., Ibba R., Brogi S., Calderone V., Butini S., Campiani G., Gemm S. The green chemistry of chalcones: Valuable sources of privileged core structures for drug discovery. Front. Chem. 2022, Vol. 10, pp. 1-22. https://doi.org/10.3389/fchem.2022.988376
21. Akbari P.M., Shah V.R. Synthesis, Characterization and Biological Evaluation of Ethyl-4'-(cyclopropane carboxamido-N-yl)-5-ary-3-oxo-3,4,5,6- tetrahydro-biphenyl-4-carboxylate. Asian Journal of Organic & Medicinal Chemistry, 2019, Vol. 4(4), p. 240-243 doi.org/10.14233/ajomc.2019.
22. Mezgebe K., Melaku Y., Mulugeta E. Synthesis and Pharmacological Activities of Chalcone and Its Derivatives Bearing N-Heterocyclic Scaffolds:AReview. ACS Omega, 2023, Vol. 8, p. 19194-19211. doi.org/10.1021/acsomega.3c01035 ACS.
23. Unnisa A., Abouzied A.S., Baratam A., Che nchu
K.N.V., Hussain T., Kunduru R.D., Banu H ., Fatima S.B., Hussian A., Selvarajan K.K. Design, synthesis, characterization, computational study and in-vitro antioxidant and anti-inflammatory activities of few novel 6-aryl substituted pyrimidine azo dyes. Arabian Journal of Chemistry, 2020, Vol. 13, p. 8638-8649. https://doi.org/10.1016/j.arabjc.2020.09.050
24. Mohsein H.F., Jaffer N.D., Hassen H.S., Kadhim A.A. Synthesis, Characterization and Anticancer Assessment of New Nitrogen-Cyclic Compounds. Egypt. J. Chem. 2022, Vol. 65(3), p. 571 - 579. https://doi.org/10.21608/ejchem.2021.9611 2.4504.
25. Amer Z. Synthesis and characterization of new Oxazine, Thiazine and Pyrazol derived from chalcones. Baghdad Science Journal. 2014, Vol. 11(2), p. 477-485.
https://doi.org/10.21123/bsi.2014.1L2.477-485.
26. Monga V., Goyal K., Steindel M., Malhotra M., Rajani D.P., Rajani S.D. Synthesis and evaluation of new chalcones, derived pyrazoline and cyclohexenone derivatives as potent antimicrobial, antitubercular and antileishmanial agents. Medicinal Chemistry Research, 2014, Vol. 23(4), p. 2019-2032. https://doi.org/10.1007/s00044-013-0803-1
27. Kadhium A.J., Mahdi S.M., Alrammahi F.A.H. Preparation and Characterization of new Azo Azo-Chalcone Ligands and their mixed ligands transition metal complexes with A study of Palladium Complex Anticancer Activity. Research J. Pharm. and Tech. 2019, Vol. 12(12), p. 59475955.
28. Sharma A., Arora S.K. A Review study on green synthesis of schiff bases. Indian J. Appl. Res. 2021, Vol. 18(2), p. 69-72. https://doi.org/10.36106/iiar/9529205.
29. Rashmi A., Ashish K., Gill N.S., Rana A.C. Quinazolinone: an overview. Int. Res. J. Pharm. 2011, Vol. 2, p. 22-28.
30. Aljamali N.M. Survey on methods of preparation and cyclization of heterocycles. Int. J. Chem. Mol. Eng. 2020, Vol. 6(92), p. 19-36
31. Mauf R.M., Sultan A.H., Farag A.M. Synthesis of Some new 2-(4-Aryliminophenoxy) N-Arylacetamide Via p-hydroxy benzaldehyde. Baghdad Science Journal. 2014, Vol. 11(2), p. 486-490.
32. Mathammal R., Sangeetha K., Sangeetha M., Mekala R., Gadheeja S. Molecular structure, vibrational, UV, NMR, HOMO-LUMO, MEP, NLO, NBO analysis of 3, 5 di tert butyl 4 hydroxy benzoic acid. Journal of Molecular Structure, 2016, Vol. 1118, p. 316-324.
33. Watson J.D., Sparkman O.D. ''Introduction to Massspectrometry'', 4th ed. John Wiley and Sons Ltd. 2007.
