Title Science and Technology Indonesia e-ISSN:2580-4391 p-ISSN:2580-4405 Vol. 8, No. 3, July 2023 Research Paper Synthesis, Characterization, and Antibacterial Activity of Some Mesalazine Derivatives Ekhlas Qanber Jasim1, Munther Abduljaleel Muhammad-Ali2*, Ayad Almakki3 1Department of Pathological Analyses, College of Science, University of Basrah, Basrah, 61004, Iraq2Department of Ecology, College of Science, University of Basrah, Basrah, 61004, Iraq3Department of Laboratory Sciences, College of Pharmacy, University of Basrah, Basrah, 61004, Iraq *Corresponding author: munther.ali@uobasrah.edu.iq, muntheralamery@yahoo.com AbstractMesalazine, often referred to as mesalamine or 5-aminosalicylic acid (5-ASA), and its derivatives are some of the first medications tobe approved for treating digestive tract inflammations, including ulcerative colitis and mild to moderate Crohn’s disease. Sulfasalazine,discovered in 1938 for therapeutic use, was the first mesalazine derivative. High yields of four different mesalazine derivatives weresynthesized, including two Schiff bases and two azo compounds. The present study involved the synthesis of Schiff bases throughthe reaction of mesalazine with pyrrole-2-carbaldehyde or indole-2-carbaldehyde, resulting in the formation of 5-(((1H-pyrrol-2-yl)methylene)amino)-2-hydroxybenzoicacid(1)or5-(((1H-indol-2-yl)methylene)amino)-2-hydroxybenzoicacid(2), respectively. Thesynthesis of azo compounds involved the coupling of mesalazine with sulfamethoxazole or pyridoxine, resulting in the formation of5-amino-2-hydroxy-3-((4-(N-(5-methylisoxazol-3-yl)sulfamoyl)phenyl)diazenyl)benzoic acid (3) or 2-hydroxy-5-((5-hydroxy-3,4-bis(hydroxymethyl)-6-methylpyridin-2-yl)diazenyl)benzoic acid (4), respectively. The identification of the synthesized compoundswas carried out using IR and 1H-NMR spectroscopy. Antibacterial assessment of the synthetic compounds was performed in vitroagainst gram-negative bacteria (such as Escherichia coli and Pseudomonas aeruginosa) and gram-positive bacteria (Staphylococcus aureus). The antibacterial activity studies demonstrated that against Escherichia coli and Staphylococcus aureus, the Schiff basecompounds are more active than azo compounds. Compound 1 showed the highest activity, resulting in a 23 mm inhibition zoneagainst E. coli at 1000 `g/mL. In contrast, the antibacterial activity of compound 2 was observed to be 25 mm against S. aureus atthe same highest concentration. KeywordsMesalazine, Schiff Bases, Azo Compounds, Antibacterial Activity, Modification of Drug Received: 18 January 2023, Accepted: 17 April 2023 https://doi.org/10.26554/sti.2023.8.3.338-343 1. INTRODUCTION Modifying the chemical molecules of commercially available medications is one of the most critical aspects of pharmacolog- ical development. Molecular modification involves changing the chemical structure of drugs away from their active site, which can impact their efficacy and ability to treat certain dis- eases. Thus, a new derivative of the drug molecule is prepared using different chemical reactions with physicochemical prop- erties other than the original drug (Ye and van Langenberg, 2015) . The substance mesalazine, used to treat inflammatory bowel diseases like Crohn’s disease and ulcerative colitis, is one essential medicine whose chemical structure has undergone modifications (Yasutomi et al., 2019) . Mesalazine has addi- tional biological activities; it has been utilized as an antioxidant against oxygen and nitrogen free radicals (Yousefi et al., 2017) , anti-ulcer (Beiranvand, 2021) , against colorectal cancer (Dixon et al., 2021) , and antimicrobial activity (Zhang et al., 2018; Cevallos et al., 2021). Several pharmaceutical dosage forms of mesalazine deriva- tives are utilized in the drug market to treat UC, focusing on aminosalicylic acids and their associated derivatives. The most important derivatives are salazosulfapyridine (SASP), ol- salazine, and mesalazine (Zhang et al., 2015) . The chemical structure of mesalazine is of great impor- tance in the process of chemical modification on this molecule, as it contains in its structure two groups, carboxyl and amine groups, and these two groups are easily subject to many types of chemical reactions, allowing the formation of many types of derivatives (Yuri et al., 2020) . Within the design of prodrugs as derivatives of the drug mesalazine, many polysaccharides were used by linking them using ester bonds of the carboxyl group because they are considered non-toxic. Through the polysaccharide compounds, it is possible to observe the muta- tion in the characteristics of these compounds through their https://crossmark.crossref.org/dialog/?doi=10.26554/sti.2023.8.3.338-343&domain=pdf https://doi.org/10.26554/sti.2023.8.3.338-343 Jasim et. al. Science and Technology Indonesia, 8 (2023) 338-343 absorption from the small intestine; it is also soluble in water (Sardo et al., 2019) . The other type of modification is on the amino group, and the prodrugs of mesalazine can be prepared by linking them with amino acids. Based on these functional groups, amino acids can be connected via an ester (Yousefi et al., 2015) or amide bond, and an azo group (Abdel Alim et al., 2005) can be synthesized. In particular, when an amide bond is used, the synthesized compound is similar in structure to a dipeptide (Monbaliu, 2016; Taheri-Ledari et al., 2022; Tosi et al., 2022). In this study, four synthesized mesalazine derivatives were tested for their potential antibacterial activity against two types of Gram-positive and Gram-negative bacteria. Two are deriva- tives of Schiff bases (1 and 2), and the other are derivatives of azo dyes (3 and 4). 2. EXPERIMENTAL SECTION 2.1 Materials The reagents and solvents utilized in this study were of reagent- grade quality and were procured from Merck and Sigma-Aldrich. Solid materials were used without additional purification, while liquid materials were subjected to double distillation. The Gallenkamp Thermal Point Apparatus was utilized to deter- mine the uncorrected melting points. The FTIR 8400S SHI- MADZU ( Japan) was utilized to record infrared spectra in KBr pellets at Basrah University’s College of Science. DMSO-d6’s 1H-NMR spectra were measured at 500 MHz using a Bruker AC 200 FT-NMR spectrometer with TMS as an internal ref- erence, (Greece). The CHN elemental analyzer flashes EA 1112 series was utilized to conduct the Elemental Microanaly- sis (CHN) on the synthesized compounds, (Thermo Finnigan). 2.2 Methods 2.2.1 Synthesis of Compounds Schiff bases Synthesis 5-(((1H-pyrrol-2-yl)methylene)amino)- 2-hydroxybenzoic acid (1) and 5-(((1H-indol-2-yl)methylene) amino)-2-hydroxybenzoic acid (2): In the mixture that contained 0.01 mole (1.51 g) of 5- amino salicylic acid that had been dissolved in 15mL of ethanol, 0.01 mole of either pyrrole-2-carboxaldehyde or indol-2-carbo xaldehyde that had also been dissolved in 15 mL of ethanol was added, and then 1 mL of glacial acetic acid was added to the mixture. The mixture was stirred continuously for sixty minutes at room temperature. To get rid of any unreacted substances, the yellow precipitate that formed, as a result, was filtered out and then washed with cold methanol. Ethanol was used to recrystallize the products that were the result (Vhanale et al., 2019; Warad et al., 2020). (1): A pale yellow crystal was obtained with a yield of 90%. The melting point was within the range of 187-189 °C. The in- frared spectrum of the compound, obtained using KBr, showed absorption bands at 3305 cm−1 (O-H), 3010 cm−1 (C-H, aro- matic), 1687 cm−1 (C=N, azomethine), 1606 cm−1, and 1508 cm−1 (C=C), as well as at 1253 cm−1 and 1145 cm−1 (C-N, C- O). The 1H NMR spectrum of the compound in DMSO-d6 so- lution displays signals at 𝛿 = 12.80 (broad, 1H, carboxylic acid), 10.39 (singlet, 1H, hydroxyl), 9.25 (singlet, 1H, amine), 8.61 (singlet, 1H, imine), and a range of signals between 6.53 and 8.13. (m, 6H, Ar-H). Anal. Calc. (Found) for C12H10N2O3 (230.22): C, 62.61 (61.95); H, 4.38 (4.54); N, 12.17 (12.32). (2): Crystal in a dark yellow color, with a yield of 92%, melting point in the range of 174-176 degrees Celsius, and the follow- ing IR (KBr) spectrum: v (cm−1) = 3386 (O-H), 3010 (C-H, aromatic), 1656 (C=N, azomethine), 1600, 1510 (C=C), 1238, 1165 (C-N, C-O). 1H nuclear magnetic resonance (DMSO- d6): = 6.92-7.90 (m, 8H, Ar-H), 8.84 (s, 1H, CH=N), 8.99 (br, 1H, NH), 10.25 (s, 1H, OH), 12.69 (br, 1H, COOH). Anal. Calc. (Found) for C16H12N2O3 (280.28): C, 68.56 (67.87); H, 4.32 (4.22); N, 9.99 (10.21). The present study involves the synthesis of two compounds, namely 5-amino-2-hydroxy-3-((4-(N-(5-methylisoxazol-3- yl)sulfamoyl)phenyl)diazenyl) benzoic acid (3) and 2-hydroxy- 5-((5-hydroxy-3,4-bis(hydroxymethyl)-6-methylpyridin-2-yl) diazenyl)benzoic acid(4). Diazotization was accomplished by dissolving 0.025 mol of 5-aminosalicylic acid or sulfamethoxazole in 5 mL of 2 M hydrochloric acid. After that, the solution was placed in an ice bath until it reached a temperature of 0-5 degrees Celsius, then kept at that temperature. A solution of sodium nitrite (5 mol, 2 g) in water (5 mL) was added drop by drop while the mixture was continuously stirred for ten minutes at the same temperature. General procedure for preparation of azo dyes: The cou- pling reaction was performed by gradually adding the diazo- nium solution of 5-aminosalicylic acid or sulfamethoxazole to the coupling component solution, which had been prepared by combining a suspension of one mmol of pyridoxine (0.2056 g) or one mmol of 5-aminosalicylic acid (0.253 g) (Scheme 1) in 10 mL of water with sodium hydroxide (0.002 mmol) dis- solved in 15 mL of water. During this procedure, the pH was between 9 and 10, while the temperature was maintained at 0 to 5 degrees Celsius. The mixture was agitated for 6 hours, and the pH was lowered to about six. Overnight, the mixture was kept. Filtration was used to collect the precipitated crude dyes, which were then washed with solvents such as water, ethanol, and acetone (Benkhaya et al., 2020; Kareem Samad, 2017). (3): Powdered orange, 80% yield; melting point below 306 degrees Celsius; infrared (KBr) spectral lines: v (cm−1) = 3412 (O-H), 1591 (C=N), 1511 (C=C), 1463 (N=N), 1300 (C-H, Aliph), 1174, 1091 (C-N, C-O). For the hydrogen atom(1H) in DMSO-d6, the NMR spectrum looks like this: = 12.56 (br, 1H, COOH), 10.40 (s, 1H, OH), 11.20 (br, 1H, NH), 6.86- 8.02 (m, 7H, Ar-H), 5.36 (s, 2H, NH2), 1.91 (s, 3H, CH3). Anal. Calc. (Found) for C17H15N5O6S (417.40): C, 48.92 (48.67); H, 3.62 (3.52); N, 16.78 (16.61). (4): The color is dark purple, the yield is 85%, the melting point is below 350 degrees Celsius, and the infrared spectrum looks like this: IR (KBr): v (cm−1) = 3425 (O-H), 1645 (C=N), 1500 (C=C), 1587 (N=N), 1384 (C-H, Aliph), 1272 (C-N, C-O). 1H NMR (DMSO-d6): 𝛿 = 12.77 (br, 1H, COOH), 10.35 © 2023 The Authors. Page 339 of 343 Jasim et. al. Science and Technology Indonesia, 8 (2023) 338-343 (s, 1H, OH), 9.79 (s, 1H, OH pyridoxine), 7.25-7.86 (m, 3H, Ar-H), 5.63 (s, 2H, OH aliphatic), 4.21 (s, 4H, CH2), 2.37 (s, 3H, CH3). Anal. Calc. (Found) for C15H15N3O6 (333.30): C, 54.05 (54.32); H, 4.54 (4.42); N, 12.61 (12.71). 2.2.2 Antibacterial Evaluation Pathogenic strains of Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli and Pseudomonas aeruginosa) were used to investigate the antibacterial activity of the pre- pared compounds using the Filter Paper Disc Diffusion Method (Kifby-Bauer Method). This method measured the inhibition zone in mm around these bacteria. A dimethyl sulfoxide sol- vent was used to prepare a stock solution of 1000 `g/mL for each compound, which was subsequently stored at 4-8 °C until utilized. The Mueller Hinton agar plates were inoculated us- ing a sterile cotton swab dipped into the inoculum. The swab was then evenly streaked in three directions across the entirety of the Petri-dish surface. Discs of filter paper measuring 6 mm in diameter were saturated with a solution of tested com- pounds at a concentration of 1000 mg/mL and various other diluted concentrations. The impregnated discs were subse- quently dried and positioned onto an agar plate inoculated with Gram-positive and Gram-negative bacteria cultures (Salman, 2019; Mohammed-Ali and Jasim, 2019). Figure 1. Compounds One and Two Synthesis 3. RESULTS AND DISCUSSION 3.1 Chemistry The synthesis of two products (1 and 2) was achieved by con- densing the 5-aminosalicylic acid compound with pyrrole-2- carboxaldehyde or indol-2-carboxaldehyde in refluxed ethanol solvent, with the addition of a tiny amount of glacial acetic acid. The resulting yellow crystals were analyzed using IR spectroscopy, revealing significant absorption broad bands at v 3305 and 3386 cm−1 for compounds (1) and (2), respectively. These bands were due to the vibrations caused by stretching of O-H for phenolic and carboxylic groups, as depicted in Fig- ure 1. The appearance of a distinct band at 1658 and 1656 cm−1 (Bartyzel, 2017) (for compounds 1 and 2, respectively) is indicative of the C=N vibrations that stretch the azomethine fragment, thereby providing compelling evidence for the for- mation of Schiff bases. Four singlet signals were found in the 1H-NMR spectrum of compound (1). Two of these signals referred to hydroxyl groups of carboxylic and phenol of salicylic fragment at 𝛿 12.80 Figure 2. Compound Three Synthesis Figure 3. Compound Four Synthesis and 10.39 ppm, respectively (Kleks et al., 2021) . The H-N bond in the pyrrole ring and the CH=N bond in the azome- thine group was responsible for two additional signals at 𝛿 9.25 and 8.61 ppm, respectively (Jasim et al., 2020) . The multiple signals observed at the 6.53-8.13 ppm range for six protons corresponded to the aromatic protons of pyrrole and salicylic rings. Figure 4. Spectrum of 1H-NMR Compound 2 Singlet signals were observed in the 1H-NMR spectrum of compound 2 at 𝛿 12.69 and 10.25 ppm. These signals were ascribed to the salicylic acid fragment’s phenolic hydroxyl and carboxylic hydroxyl protons. Another two singlet signals were observed at chemical shifts of 𝛿 8.99 and 8.84 ppm, attributed to the N-H of indole and CH=N of the azomethine group, respectively. Figure 4 shows several aromatic signals between 𝛿 6.92 and 7.90 ppm, caused by the eight indole and salicylic acid group protons. Aromatic amines react with concentrated HCl and sodium nitrite at 0-5 °C to produce diazonium salts. Sulfamethoxazole or 5-aminosalicylic acid subjected to diazotization process to give the corresponding diazonium salts. Another step in the © 2023 The Authors. Page 340 of 343 Jasim et. al. Science and Technology Indonesia, 8 (2023) 338-343 synthesis of an azo compound is coupling reaction with rich electron aromatic system, diazonium salt of sulfamethoxazole reacts with 5-aminosalicylic acid to give the azo compound (3). Azo compound (4) was synthesized by reaction of diazonium salt of 5-aminosalicylic acid with pyridoxine with characteristic bright colored crystals, as shown in Figure 2 and 3. Figure 5. (A) IZ of Compound (1) Against E. coli, (B) IZ of Compound (4) Against S. aureus Figure 6. Inhibition Zone of the Studied Compounds Against S. aureus The IR spectra of the azo compounds gave broad peaks at the range about v 3400 cm−1 due to stretching vibration of O-H of carboxylic group overlapped with phenolic group. An- other characteristic strong-medium peak attributed to stretch- ing vibration of azo group appeared at 1463 and 1587 cm−1 for compound (3) and (4), respectively. 1H-NMR of the compound (3) gave two singlet signals in download field at 𝛿 12.56 and 10.40 ppm attributed to hy- droxyl group of carboxylic and phenolic groups, respectively. Another singlet signals at 𝛿 11.20 ppm attributed to N-H pro- ton of amide in sulfa fragment and at 𝛿 5.36 ppm due to two protons of NH2 group in salicylic fragment. Aromatic protons gave multiplet signals at the range 𝛿 6.86-8.02 ppm referred to seven protons in each sulfa and salicylic fragments, and finally, singlet signal at highfield range 𝛿 1.91 ppm attributed to three protons of methyl group, as shown in Table 1. The 1H-NMR analysis of compound 4 yielded a complex spectrum featuring two singlet signals at 𝛿 12.77 and 10.35 ppm, which were attributed to the hydroxyl proton of the Figure 7. Inhibition Zone of the Studied Compounds Against E. coli Figure 8. Inhibition Zone of the Studied Compounds Against P. aeruginosa phenolic and carboxylic groups, respectively. A singlet signal at 𝛿 9.79 ppm was also observed, which was attributed to a single phenolic proton of the pyridoxine group. Multiplet signals at 𝛿 6.62-7.37 ppm referred to three protons of salicylic ring, singlet signal 𝛿 5.63 ppm due to two protons of aliphatic alcohol, singlet signal referred to four aliphatic protons of two groups of methylene in -CH2-OH fragment in pyridoxine ring at 𝛿 4.21 ppm, Finally, as shown in Table 1, the singlet signal at 𝛿 2.37 corresponds to the three protons of a methyl group in the pyridoxine ring. 3.2 Antibacterial Sensitivity Test The activity of the synthesized compound was assessed through the disc diffusion method utilizing various concentrations (125, 250, 500, and 1000 `g/mL) while using DMSO as a con- trol. The results were then compared to the standard drug mesalazine. Against S. aureus bacteria, compound (2) and (4) showed higher activity (25 and 19 mm, respectively) as com- pared other compounds. Against E. coli bacteria, the com- pounds (1, 2 and 4) gave strong inhibition zone (23, 18 and 19 mm, respectively) as compared with other compounds, as shown in Figure 5. The synthesized compounds exhibited con- siderable efficacy compared to the standard mesalazine drug, potentially due to the bacteria’s resistance to the commercial © 2023 The Authors. Page 341 of 343 Jasim et. al. Science and Technology Indonesia, 8 (2023) 338-343 Table 1. 1H-NMR Synthetic Compound’s Data Compounds 𝛿 (ppm) -COOH -OH -NH -CH=N Aromatic Others 1 12.80 (s) 10.39 (s) 9.25 (s) 8.61 (s) 6.53-8.13 (m) - 2 12.69 (s) 10.25 (s) 8.99 (s) 8.84 (s) 6.92-7.90 (m) - 3 12.56 (s) 10.40 (s) 11.20 (s) - 6.86-8.02 (m) 5.36 (s) -NH2, 1.91 (s) -CH3 4 12.77 (s) 10.35 (s) - - 7.25-7.86 (m) Pyridine ring, 9.79 (s) -OH, 5.63 (s) aliph. -OH, 4.21 (s) -CH2-, 2.37 (s) -CH3 ppm: part per million, s: singlet signal, m: multiplet signal Table 2. In Vitro Antibacterial Sensitivity Test of Synthesized Compounds in DMSO Concentration S. aureus E. coli P. aeruginosa (`g/mL) IZ (mm) Compound (1) 1000 16 23 11 500 10 19 8 250 Nil 15 Nil 125 Nil 11 Nil IZ (mm) Compound (2) 1000 25 18 14 500 20 12 10 250 17 9 Nil 125 12 Nil Nil IZ (mm) Compound (3) 1000 12 10 Nil 500 8 8 Nil 250 Nil Nil Nil 125 Nil Nil Nil IZ (mm) Compound (4) 1000 19 19 12 500 15 17 7 250 10 17 Nil 125 8 14 Nil IZ (mm) Mesalazine 1000 Nil 14 12 500 Nil 8 8 250 Nil Nil Nil 125 Nil Nil Nil drug. Overall view on the activity, the best activity is 23 mm attributed to (1) against E. coli and 25 mm for compound (2) against to S. aureus, as shown in Figure 6-8. Table 2 repre- sents the data of in vitro antibacterial activity of synthesized compounds in DMSO. Schiff bases with a salicylic-imine moiety are also effective in the mechanism of inhibition on bacterial growth. Com- pounds 1 and 2 belonging to this category of Schiff bases ex- hibited complete growth inhibition against S. aureus and E. coli (Tyagi et al., 2017; Kumar and Bansal, 2021). Regarding P. aeruginosa, the highest antibacterial activity was detected by compound 2 with a minimum zone of inhibi- tion of about 14 mm which was the weakest inhibition zone among other studied bacteria, moreover, P. aeruginosa shows complete resistance to compound 3 whatever its concentration was. 4. CONCLUSION The Schiff bases, denoted as compounds 1 and 2, and the azo compounds, designated as compounds 3 and 4, were success- fully synthesized with high yield and purity. Subsequently, spectroscopic techniques were employed to characterize these compounds. The inhibition zone method evaluated the syn- thesized compounds’ antibacterial sensitivity. Compounds 1, 2, and 4 demonstrated intense activity against S. aureus and E. coli, while compound 3 exhibited moderate activity. The bacteria P. aeruginosa showed high resistance against the syn- thesized compounds. The standard drug mesalazine showed weak activity under the same experimental conditions, which referred to the high resistance of all three strains of bacteria to this known drug. Another finding from this study is that the ability of synthesized compounds to inhibit bacterial growth increased with increased concentration. 5. ACKNOWLEDGMENT The authors thank the Department of Pathological Analyses within the College of Science at the University of Basra for their valuable support and guidance. REFERENCES Abdel Alim, A. M., Abdel, A. N. A. El Shorbagi, S. G. Ab- del Moty, and H. H. M. Abdel Allah (2005). Synthesis and Anti-inflammatory Testing of some New Compounds Incorporating 5-aminosalicylic acid (5-ASA) as Potential Prodrugs. Archives of Pharmacal Research, 28; 637–647 Bartyzel, A. (2017). Synthesis, Thermal Study and Some Properties of N 2 O 4-Donor Schiff Base and its Mn (III), Co (II), Ni (II), Cu (II) and Zn (II) Complexes. Journal of Thermal Analysis and Calorimetry, 127; 2133–2147 Beiranvand, M. (2021). A Review of the Biological and Phar- macological Activities of Mesalazine or 5-aminosalicylic acid © 2023 The Authors. Page 342 of 343 Jasim et. al. Science and Technology Indonesia, 8 (2023) 338-343 (5-ASA): An Anti-ulcer and Anti-oxidant Drug. Inflam- mopharmacology, 29(5); 1279–1290 Benkhaya, S., S. M’rabet, and A. El Harfi (2020). Classifica- tions, Properties, Recent Synthesis and Applications of Azo Dyes. Heliyon, 6(1); 03271 Cevallos, S. A., J. Y. Lee, E. M. Velazquez, N. J. Foegeding, C. D. Shelton, C. R. Tiffany, B. H. Parry, A. R. Stull Lane, E. E. Olsan, and H. P. Savage (2021). 5-Aminosalicylic Acid Ameliorates Colitis and Checks Dysbiotic Escherichia coli Expansion by Activating PPAR-𝛾 Signaling in the Intestinal Epithelium. Mbio, 12(1); 03227–27 Dixon, S. W., T. J. Collard, E. M. H. Mortensson, D. N. Legge, A. C. Chambers, A. Greenhough, T. J. Creed, and A. C. Williams (2021). 5-Aminosalicylic Acid Inhibits Stem Cell Function in Human Adenoma-derived Cells: Implications for Chemoprophylaxis in Colorectal Tumorigenesis. British Journal of Cancer, 124(12); 1959–1969 Jasim, E. Q., H. K. Dhaif, and M. A. Muhammad-Ali (2020). Synthesis, Characterization, Antifungal Activity and Structure-activity Relationships: Study of Some Mono- and Di-schiff Bases. Periodico Tche Quimica (Online), 17(34); 528–540 Kareem Samad, M. (2017). Synthesis, Characterization and Dying Performance Studies of Some Azo Dyes Derived from m-phenylenediamine. Journal of Pure and Applied Sci- ences, 28(6); 148–157 Kleks, G., D. C. Holland, J. Porter, and A. R. Carroll (2021). Natural Products Dereplication by Diffusion Ordered NMR Spectroscopy (DOSY). Chemical Science, 12(32); 10930– 10943 Kumar, S. and H. Bansal (2021). A Review on Synthesis and Antimicrobial Activity of Schiff Bases. International Journal of Innovative Science, Engineering and Technology, 8(7); 46–64. Mohammed-Ali, M. A. and E. Q. Jasim (2019). Synthesis, Characterization, Antimicrobial Activity and Theoretical Studies of New Polymeric Schiff-base. Journal of The Chemi- cal Society of Pakistan, 41(04); 591 Monbaliu, J. C. M. (2016). The Chemistry of Benzotriazole Deriva- tives. Springer Salman, H. H. (2019). Antimicrobial Evaluation of Some New Nitrone Compounds Derived from Glyoxal. International Journal of Green Pharmacy, 13(3); 275 Sardo, H. S., F. Saremnejad, S. Bagheri, A. Akhgari, H. A. Garekani, and F. Sadeghi (2019). A Review on 5- aminosalicylic Acid Colon-targeted Oral Drug Delivery Sys- tems. International Journal of Pharmaceutics, 558; 367–379 Taheri-Ledari, R., F. R. Asl, M. Saeidirad, A. Kashtiaray, and A. Maleki (2022). Convenient Synthesis of Dipeptide Struc- tures in Solution Phase Assisted by a Thioaza Functionalized Magnetic Nanocatalyst. Scientific Reports, 12(1); 4719 Tosi, E., J. M. Campagne, and R. M. de Figueiredo (2022). Amine Activation:“Inverse” Dipeptide Synthesis and Amide Function Formation through Activated Amino Compounds. The Journal of Organic Chemistry, 87(18); 12148–12163 Tyagi, M., P. Tyagi, and S. Chandra (2017). Synthesis, Spectral and Antibacterial Activity of Co (II), Ni (II) and Zn (II) Complexes with 2-hydroxy-benzoic acid (3, 4-dihydro-2H- naphthalen-1-ylidene)-hydrazide. Applied Organometallic Chemistry, 31(12); 3880 Vhanale, B., N. Deshmukh, and A. Shinde (2019). Synthe- sis, Characterization, Spectroscopic Studies and Biologi- cal Evaluation of Schiff Bases Derived from 1–hydroxy-2- acetonapthanone. Heliyon, 5(11); 02774 Warad, I., O. Ali, A. Al Ali, N. A. Jaradat, F. Hussein, L. Abdallah, N. Al-Zaqri, A. Alsalme, and F. A. Alharthi (2020). Synthesis and Spectral Identification of Three Schiff bases with a 2-(piperazin-1-yl)-N-(thiophen-2-yl methy- lene) Ethanamine Moiety Acting as Novel Pancreatic Lipase Inhibitors: Thermal, DFT, Antioxidant, Antibacterial, and Molecular Docking Investigations. Molecules, 25(9); 2253 Yasutomi, E., S. Hiraoka, S. Yamamoto, S. Oka, M. Hi- rai, Y. Yamasaki, T. Inokuchi, H. Kinugasa, M. Takahara, and K. Harada (2019). Switching between Three Types of Mesalazine Formulation and Sulfasalazine in Patients with Active Ulcerative Colitis who have Already Received High-dose Treatment with these Agents. Journal of Clinical Medicine, 8(12); 2109 Ye, B. and D. R. van Langenberg (2015). Mesalazine Prepara- tions for the Treatment of Ulcerative Colitis: Are All Cre- ated Equal? World Journal of Gastrointestinal Pharmacology and Therapeutics, 6(4); 137 Yousefi, S., S. Bayat, M. B. A. Rahman, Z. Ibrahim, and E. Ab- dulmalek (2017). Synthesis and In Vitro Bioactivity Eval- uation of New Galactose and Fructose Ester Derivatives of 5-Aminosalicylic Acid. Chemistry and biodiversity, 14(4); 1600362 Yousefi, S., S. Bayat, M. B. A. Rahman, I. S. Ismail, E. Saki, S. W. Leong, and E. Abdulmalek (2015). Synthesis, Bioactiv- ity Evaluation, and Docking Study of 5-aminosalicylic Acid’s Fatty Acid Derivatives. Monatshefte für Chemie-Chemical Monthly, 146; 2139–2149 Yuri, T., Y. Kono, T. Okada, T. Terada, S. Miyauchi, and T. Fu- jita (2020). Transport Characteristics of 5-Aminosalicylic Acid Derivatives Conjugated with Amino Acids via Human H+-coupled Oligopeptide Transporter PEPT1. Biological and Pharmaceutical Bulletin, 43(4); 697–706 Zhang, S., J. Fu, B. Dogan, E. J. Scherl, and K. W. Simpson (2018). 5-Aminosalicylic Acid Downregulates the Growth and Virulence of Escherichia coli Associated with IBD and Colorectal Cancer, and Upregulates Host Anti-inflammatory Activity. The Journal of Antibiotics, 71(11); 950–961 Zhang, Z. H., H. J. Zhang, A. J. Deng, B. Wang, Z. H. Li, Y. Liu, L. Q. Wu, W. J. Wang, and H. L. Qin (2015). Syn- thesis and Structure–Activity Relationships of Quaternary Coptisine Derivatives as Potential Anti-ulcerative Colitis Agents. Journal of Medicinal Chemistry, 58(18); 7557–7571 © 2023 The Authors. Page 343 of 343 INTRODUCTION EXPERIMENTAL SECTION Materials Methods Synthesis of Compounds Antibacterial Evaluation RESULTS AND DISCUSSION Chemistry Antibacterial Sensitivity Test CONCLUSION ACKNOWLEDGMENT