Synthesis, Characterization, and Study of Biological Activity of Oxazepine Compounds Derived From 1,3,4-Oxadiazole
Synthesis, Characterization, and Study of Biological Activity of Oxazepine Compounds Derived From 1,3,4-Oxadiazole
Synthesis, Characterization, and Study of Biological Activity of Oxazepine Compounds Derived From 1,3,4-Oxadiazole
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compounds is a key aspect of their allure. 2.3. Preparation of oxazepine derivatives
These compounds exhibit a wide range of (M32-M37) [18, 19]
biological activities, making them of interest in A mixture of 0.2 grams (0.0005 moles) of pre-
medicinal chemistry [8, 9]. From potential dissolved hydrazide bases in 25 mL of dry
pharmaceutical agents to innovative materials, benzene was combined with (0.098 grams,
oxazepine compounds offer a versatile palette 0.001 moles) of malic anhydride dissolved in
for researchers to explore and exploit [10]. This 15 mL of the same solvent. The mixture was
topic explores the biological and medicinal refluxed for a period of (6-10) hours, and the
significance of oxazepine compounds, completion of the reaction was verified using
highlighting their interactions with biological Thin-Layer Chromatography (TLC) technique.
systems and potential therapeutic applications After cooling, the mixture was filtered, washed
[11, 12]. From anticonvulsant properties to with cold water, and the resulting crystals were
anti-inflammatory effects, the pharmacological recrystallized using methanol [30, 31]. Table
potential of oxazepine compounds is a (1) illustrates the physical properties of the
promising avenue for further research and oxazepine derivatives.
development in the field of medicine [13, 14].
In conclusion, oxazepine compounds stand as a 2.4. Biological activity study [20, 21]
captivating subject within the realm of organic Two types of pathogenic bacteria were used in
chemistry, with their unique molecular this study, one of which is Gram-positive,
structure, diverse synthesis methods, and which is Staphylococcus aureus, and one of
potential applications across various domains which is Gram-negative, which is Escherichia
[15, 16]. As researchers continue to unravel the coli. These bacteria were taken from the
mysteries surrounding these compounds, the laboratories of the College of Education for
possibilities for advancements in medicine, Pure Sciences, Department of Life Sciences,
materials science, and beyond appear and the culture medium was used, a type of
boundless, making oxazepines a topic ripe for Multer Hinton Agar [39]. It is used to measure
exploration and discovery [17]. and determine the minimum inhibitory
2. Experimental: concentration (MIC), and chemical solutions of
2.1. Material: All chemicals used in this (M32, M34, M37) were prepared in
work were purchased from Fluka, concentrations (25, 50, 75) mg/ml and using a
Aldrich, and BDH and used without solvent Dimethyl sulfoxide (DMSO). The
further purification. sensitivity test for the bacteria isolates used in
the study was carried out by diffusion method
2.2. Devices used: The melting points were in the nutrient medium Mueller-Hinton agar.
measured using Electrothermal Melting The medium was prepared and sterilized by
Apparatus 9300. Shimadzu FT-IR 8400S autoclave, then distributed in dishes and left to
spectrophotometer with a scale of (400- harden, then small pits were made at a rate of
4000) cm-1 by KBr disc. 1H-NMR and
13 four holes in each plate. Then it was incubated
C-NMR spectra on Bruker instruments
at (37 0C) for a period of (24 hours). The
running at 400 MHZ. Shimadzu UV-1800 results were read on the next day to show the
spectrophotometer with quartz cells and derivatives sensitivity derivatives used, which
in the range of 200-800 nanometers, depends on the diameter of the inhibition
Tikrit University. Thin Layer evident in the dishes around the holes used, as
Chromatography (TLC) was performed the increase in diameter Inhibition means the
using Fluka silica gel plates with 0.2 mm increase in the biological activity of the
thickness, activated with fluorescent prepared compounds and compare that with the
silica gel G, and visualization was diameter of inhibition for antibiotics [22, 23].
achieved using UV light.
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3. Results and discussion
In this study, pentagonal rings of oxazepine derivatives were synthesized by reacting one mole of
Schiff bases derivatives with two moles of malic anhydride, as depicted in Scheme 1.
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evaluated against two types of bacteria[30].: Escherichia coli and Staphylococcus aureus, selected due
to their medical significance as they cause various diseases. Additionally, these bacteria differ in their
antibiotic resistance profiles [31, 32]. The biological activity of prepared compounds was assessed
using the agar well diffusion method, measuring the inhibition zone diameter [33, 34]. The results
indicate that the prepared compounds possess the ability to inhibit the growth of both Gram-positive
and Gram-negative bacteria to varying degrees. The compounds exhibited significant inhibitory
activity against Escherichia coli and showed excellent inhibitory effects against Staphylococcus aureus
[35,36]. The relationship between concentration and inhibition was dose-dependent, with higher
inhibition percentages observed at a concentration of 75 milligrams per milliliter, as presented in Table
(3)
Table (1): Some physical properties of tetrazole derivatives.
Molecular Formula/ Time
Comp. R Color M.P (0C) Rf Y. %
M.Wt g/mol (h)
M32 Br C32H18N6O8Br2 / 774.34 Light brown 6 151-153 0.92 81
M33 Cl C32H18N6O8Cl2 / 685.43 Yellow 8 307-309 0.25 84
M34 NO2 C32H18N8O12 / 706.54 Yellow 10 288-289 0.48 76
M35 OH C32H20N6O10 / 648.54 Dark brown 7 239-240 0.38 62
M36 N(CH3)2 C36H30N8O8 / 702.68 Dark yellow 9 216-218 0.81 80
M37 CH3 C34H24N6O8 / 644.60 Orange 9 202-203 0.86 77
Table (2): Uv-Viv and FT-IR absorption results for oxazepine derivatives (M32-M37)
IR (KBr) cm-1
λ1,λ2
Comp. C=O
R max C-O, C-
No. C-H Lactone, C=N C=C Others
(nm) N
Lactam
M8 Br 235, 370 3054, 2913 1718, 1670 1631 1599, 1475 1308, 1246 (C-Br) 592
M9 Cl 210, 386 3091, 2943 1724, 1664 1622 1575, 1479 1371, 1284 (C-Cl) 729
(NO2) 1536,
M10 NO2 228, 302 3092, 2911 1727, 1671 1624 1599, 1496 1376, 1280
1321
M11 OH 256, 337 3087, 2965 1719, 1658 1626 1598, 1477 1345, 1243 (OH) 3400
(CH3) 2948,
M12 N(CH3)2 257, 299 3068, 2948 1724, 1674 1635 1593, 1492 1344, 1282
2844
(CH3) 2991,
M13 CH3 233, 321 3066, 2991 1725, 1666 1630 1589, 1497 1380, 1249
2875
Table (7): Biological effectiveness of prepared compounds and control treatments (inhibition in
mm).
Comp. No. Escherichia coil Staphylococcus aureus
Conc. mg/ml 25 50 75 25 50 75
M32 16 19 20 14 17 19
M34 15 16 21 15 19 22
M37 14 17 22 18 19 20
Amoxicillin 14 17 24 10 14 22
Ampicillin 10 16 22 14 20 24
Ciprofloxacin 12 17 21 15 18 21
Blank disk 0 0 0 0 0 0
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90
%T
75
993.27
906.48
1253.64
2837.09
729.04
497.60
1051.13
694.33
831.26
580.53
2943.17
1527.52
60
1107.06
1724.24
3091.68
1371.29
1166.85
1622.02
1479.30
1284.50
1575.73
1664.45
45
%T
90
567.03
80
680.83
815.83
513.03
2948.96
734.83
979.77
1085.85
1521.73
1166.85
1593.09
2844.81
3068.53
1635.52
70
1413.72
1282.57
1724.24
1492.80
1344.29
1674.10
60
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