Salicylic acid heterocyclic derivatives: chemical synthesis and biological activity

Authors

Rawaa Hefdi Zaooli, Department of Chemistry, College of Science, University of Babylon,,IRAQ
Marwa Abdulameer Mseer, Department of Chemistry, College of Science, University of Babylon,,IRAQFollow
Amneen Mohammed Alsayegh, Department of Chemistry, College of Science, University of Babylon,,IRAQ

Abstract

Before a drug can be widely used, it must go through a long development process, starting from the discovery of the active ingredient and continuing with tests to confirm its safety and effectiveness. In this study, new olsalazine derivatives were synthesized, containing a fused morpholine-3-one ring and two five-membered heterocyclic rings (thiadiazole and oxadiazole). Common and readily available materials, such as salicylic acid (to prepare 2-hydroxy-5-nitrobenzoic acid) and inexpensive catalysts, were used to synthesize compounds from the first, 5,5'-(diazene-1,2-diyl)bis(2-hydroxy-3-nitrobenzoic acid) (A1), to the seventh, 6,6'-(diazene-1,2-diyl)bis(N-(4-(5-amino-1,3,4-oxadiazol-2-yl)phenyl)-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazine-8-carboxamide) (A7).

Each compound was characterized by FT-IR and ¹H-NMR spectroscopy, along with physical properties such as melting point and color. All compounds showed positive results, and their antibacterial activity was tested against Escherichia coli and Staphylococcus aureus, with several demonstrating effective inhibition.

Recommended Citation

Zaooli, Rawaa Hefdi; Mseer, Marwa Abdulameer; and Alsayegh, Amneen Mohammed (2026) "Salicylic acid heterocyclic derivatives: chemical synthesis and biological activity," Al-Bahir: Vol. 8: Iss. 1, Article 4.
Available at: https://doi.org/10.55810/2313-0083.1114

References

[1] Mallappa, Chahar M, Choudhary N, Yadav KK, Qasim MT, Zairov R, et al. Recent advances in the synthesis of nitrogencontaining heterocyclic compounds via multicomponent reaction and their emerging biological applications: a review. J Iran Chem Soc 2025;22(1):1—33. https://doi.org/10. 1007/s13738-024-03142-3.

[2] De Joarder D, Sarkar R, Maiti DK. Synthesis of bioactive heterocycles involving heterogeneous catalysis in water. Aqueous-Mediated Synth Bioact Heterocycles 2024;2(1):307. https://doi.org/10.1039/x0xx00000x.

[3] Duc DX, QuocNVan. Isolation, bioactivities, and synthesis of lamellarin alkaloids: a review. Curr Org Chem 2022;26(10): 961—90. https://doi.org/10.2174/1385272826666220516114926.

[4] Gupta RR, Kumar M, Gupta V. Heterocyclic chemistry: volume II: five-membered heterocycles. Springer Science & Business Media; 2013.

[5] Ali Y, HamidSA, Rashid U. Biomedical applications of aromatic azo compounds. Mini Rev Med Chem 2018;18(18):1548—58. https://doi.org/10.2174/1385272826666220516114926.

[6] Li Petri G, Raimondi MV, Spano V, Holl R, Barraja P, Montalbano A. Pyrrolidine in drug discovery: a versatile scaffold for novel biologically active compounds. Top Curr Chem 2021;379(5):34. https://doi.org/10.1007/s41061- 021-00347-5.

[7] Giles RL, Nkansah RA, Looper RE. Synthesis of 2-Thio-and 2-Oxoimidazoles via Cascade addition cycloisomerization reactions of propargylcyanamides. J Org Chem 2010;75(1): 261—4. https://doi.org/10.1021/jo902326d.

[8] Rasool SR, Aljamali NM, Al-Zuhairi AJ. Guanine substituted heterocyclic derivatives as bioactive compounds. Biochem Cell Arch 2020;20(Supplement 2):3651—5. https://doi.org/10.1021/jo902326d.

[9] Naz S, Shah FA, Nadeem H, Sarwar S, Tan Z, Imran M, et al. Amino acid conjugates of aminothiazole and aminopyridine as potential anticancer agents: synthesis, molecular docking and in vitro evaluation. Drug Des Devel Ther 2021:1459—76. https://doi.org/10.2147/DDDT.S297013.

[10] Cortez-Maya S, Pedro-Hernandez LD, Martínez-Klimova E, Ramírez- Apan T, Martínez-García M. Anticancer activity of water-soluble olsalazine-PAMAM-dendrimer-salicylic acidconjugates. Biomolecules 2019;9(8):360. https://doi.org/10. 3390/biom9080360.

[11] Sanad MH, Marzook FAM, Challan SB, Essam HM, Farag AB. Radioiodination, and biological assessment of olsalazine, as a highly selective radiotracer for ulcerative colitis imaging in mice. Arab J Nucl Sci Appl 2023;56(3): 105—20. https://doi.org/10.21608/ajnsa.2022.163538.1639.

[12] Romero-Castro A, Gutierrez-Sanchez M, Correa-Basurto J, Rosales Hernandez MC, Padilla Martínez II, Mendieta- Wejebe JE. Pharmacokinetics in wistar rats of 5-[(4-carboxybutanoyl) amino]-2-hydroxybenzoic acid: a novel synthetic derivative of 5-aminosalicylic acid (5-ASA) with possible anti-inflammatory activity. PLoS One 2016;11(7):e0159889. https://doi.org/10.1371/journal.pone.0159889.

[13] V N, Fedoseeva VG, Verochkina EA. The reactions of p- Tosylmethyl isocyanide with aldehydes in the synthesis of heterocyclic compounds: a review. Mini Rev Org Chem 2023;20(4):372—93. https://doi.org/10.2174/1570193X19999220 523113243.

[14] Mishra AK, Baek KH. Salicylic acid biosynthesis and metabolism: a divergent pathway for plants and bacteria. Biomolecules 2021;11(5). https://doi.org/10.3390/biom1105 0705.

[15]https://pubs.acs.org/doi/abs/10.1021/acs.orglett.2c02066#:~: text=4*Done%20Derivatives-, Masahiro%20Abe, Kiyofumi %20Inamoto *. Gold(I)-Catalyzed Heteroannulation of Salicylic Amides with Alkynes: Synthesis of 1,3-Benzoxazin-4- one Derivatives. . doi:10.1021/acs.orglett.2c02066

. [16] Abe M, Kawamoto M, Inoue M, Kimachi T, Inamoto K. Gold (I)-Catalyzed heteroannulation of salicylic amides with alkynes: synthesis of 1,3-Benzoxazin-4-one derivatives. Org Lett [Internet] 2022 Aug 12;24(31):5684—7. https://doi.org/10. 1021/acs.orglett.2c02066.

[17] Muheyuddeen G, Khan MY, Ahmad T, Srivastava S, Verma S, Ansari MS, et al. Design, synthesis, and biological evaluation of novel imidazole derivatives as analgesic and anti-inflammatory agents: experimental and molecular docking insights. Sci Rep [Internet] 2024;14(1):23121. https:// doi.org/10.1038/s41598-024-72399-8.

[18] Chugh V, Pandey G, Rautela R, Mohan C. Heterocyclic compounds containing thiazole ring as important material in medicinal chemistry. Mater Today Proc 2022;69:478—81. https://doi.org/10.1016/j.matpr.2022.09.150.

[19] Ahmed SM, Hasan HM. Archive of SID. ir. 2023. https://doi. org/10.26655/JMCHEMSCI.2023.7.6.

[20] AL-Abayechi MMH, AL-Zuhairi AJ, AL-Baiati MN. Synthesis and identification of a novel hyper branched polymers containing melamine derivative. In: IOP conference series: materials science and engineering. IOP Publishing; 2019. p. 12092. https://doi.org/10.1088/1757-899X/571/1/ 012092.

[21] Pierozan P, Colín-Gonzalez AL, Biasibetti H, da Silva JC, Wyse A, Wajner M, et al. Toxic synergism between quinolinic acid and glutaric acid in neuronal cells is mediated by oxidative stress: insights to a new toxic model. Mol Neurobiol 2018;55(6):5362—76. https://doi.org/10.1007/s12035- 017-0761-6.

[22] dos Santos JM, Visentin APV, Scariot FJ, Echeverrigaray S, Salvador M, Branco CS. The effect of different polyphenols against neurotoxicity induced by quinolinic acid in U87-MG glial cells. Res Soc Dev 2022;11(1). https://doi.org/10.33448/ rsd-v11i1.24865.

[23] Orozco-Morales M, Hernandez-Pedro NY, Barrios-Bernal P, Arrieta O, Ruiz-Godoy LM, Aschner M, et al. S-allylcysteine induces cytotoxic effects in two human lung cancer cell lines via induction of oxidative damage, downregulation of Nrf2 and NF-κB, and apoptosis. Anti Cancer Drugs 2021;32(2): 117—26. https://doi.org/10.1097/CAD.0000000000001015.

[24] Ali Y, Hamid SA, Rashid U. Biomedical applications of aromatic azo compounds. Mini Rev Med Chem 2018;18 (18):1548—58. https://doi.org/10.2174/13895575186661805241 13111.