New β-Lactam Compounds from Sulfadoxine Drug: Synthesis, Characterization and Biological Activity

Nada Ali Salih; Nadia Sadiq Majeed

doi:10.22146/ijc.115424

New β-Lactam Compounds from Sulfadoxine Drug: Synthesis, Characterization and Biological Activity

https://doi.org/10.22146/ijc.115424

Nada Ali Salih^(1*), Nadia Sadiq Majeed⁽²⁾

(1) Department of Chemistry, Faculty of Education for Women, University of Kufa, Kufa, Najaf 54001, Iraq
(2) Department of Chemistry, Faculty of Education for Women, University of Kufa, Kufa, Najaf 54001, Iraq
(*) Corresponding Author

Abstract

Using ring-closure processes, new heterocyclic β-lactam derivatives of sulfadoxine were created. Sulfadoxine was reacted with several aromatic aldehydes under reflux in ethanol with glacial acetic acid to generate Schiff base intermediates (E6–E9). The β-lactam derivatives (E11–E14) were obtained by treating these intermediates with chloroacetyl chloride at 5–10 °C while triethylamine was present. The FTIR, ¹H-NMR and ¹³C-NMR analyses were used to confirm the structures. Significant antioxidant activity was demonstrated by biological examination, with compounds E11 and E14 outperforming ascorbic acid (E11: 70.99–78.05% inhibition). Electron-rich functional groups that counteract free radicals are associated with the increased activity. These results imply that the β-lactam derivatization of sulfadoxine and Schiff base creation are efficient methods for producing bioactive heterocyclic compounds with possible medicinal uses.

Keywords

sulfadoxine drug; heterocyclic compounds; β-lactam; biological activity; molecular docking

Full Text:

Full Text PDF Full Text PDF-Suppl. Data

References

[1] Kokre, S.J., Kavalapure, R.S., Huddi, S.S., Gharge, S., Alegaon, S.G., Ranade, S.D., Maste, M.M., Wong, L. S., Ramu, R., and Venu, D., 2025, Sulfonamides: A versatile scaffold for diverse biological activity, Results Chem., 18, 102858.

[2] Alani, B.G., Salim, K.S., Mahdi, A.S., and Al-Temimi, A.A., 2024, Sulfonamide derivatives: Synthesis and applications, Int. J. Front. Chem. Pharm. Res., 4 (1), 1–15.‏‏

[3] Fernández-Villa, D., Aguilar, M.R., and Rojo, L., 2019, Folic acid antagonists: Antimicrobial and immunomodulating mechanisms and applications, Int. J. Mol. Sci., 20 (20), 4996.‏

[4] Bisharat, H., Ahmad, Z., Ahsan, A., Fatima, I., Haq, Z., Azam, T., and Ahmad, F., 2025, The evolving role of sulfonamides in medicine and drug development: A brief review, Adv. J. Chem., Sect. B, 7 (2), 130–150.

[5] Chhablani, A., Jain, V., and Makasana, J., 2025, Sulfonamides: Historical perspectives, therapeutic insights, applications, challenges, and synthetic strategies, ChemistrySelect, 10 (29), e02122.‏

[6] Zafar, W., Sumrra, S.H., Hassan, A.U., and Chohan, Z.H., 2023, A review on ‘sulfonamides’: Their chemistry and pharmacological potentials for designing therapeutic drugs in medical science, J. Coord. Chem., 76 (5-6), 546–580.‏

[7] Subasi, N.T., 2025, “A Comprehensive Review on Schiff Bases: Development Process, Green Synthetic Strategies, and Versatile Applications” in Schiff Bases-Recent Developments and Application Areas, IntechOpen, London, UK.‏

[8] Priyangga, K.T.A., Kurniawan, Y.S., Yuliati, L., Purwono, B., Wahyuningsih, T.D., and Lintang, H.O., 2021, Novel luminescent Schiff’s base derivative with an azo moiety for ultraselective and sensitive chemosensor of Fe³⁺ ions, Luminscence, 36, 1239–1248.

[9] Divya Mohan, R., Sarukrishna, S., Babu, A.S., Santhosh, D., Ahsana Fathima, S., and Parvathy, B., 2026, A review of ligand denticity in copper–Schiff Base complexes: Structural tuning toward enhanced antioxidant activity, Inorg. Chim. Acta, 590, 122980.‏

[10] Moanta, A., 2025, Classification, synthesis, isomerism, and spectral characterization of Schiff bases, Mini-Rev. Org. Chem., 22 (7), 718–737.

[11] Shaaban, S., Yousef, T.A., Althikrallah, H.A., Al-Faiyz, Y.S., Elghamry, I., Sharaky, M., Alnajjar, R., and Al-Karmalawy, A.A.,2025, Unveiling the anti-inflammatory potential of organoselenium Schiff bases: Computational and in vitro studies, New J. Chem., 49 (1), 321–331.‏

[12] Bufarwa, S.M., El-Sefait, R.M., Thbayh, D.K., Belaidi, M., Al-Shemary, R.K., Abdusamea, R.M., El-Ajaily, M.M., Fiser, B., Bader, H.A., Saleh, A.A., and Bufarwa, M.M., 2025, Antituberculosis, antimicrobial, antioxidant, cytotoxicity and anti-inflammatory activity of Schiff base derived from 2,3-diaminophenazine moiety and its metal(II) complexes: structural elucidation, computational aspects, and biological evaluation, Rev. Inorg. Chem., 45 (1), 105–124.‏

[13] Dhanya, T.M., Prathapachandra Kurup, M.R., Rajimon, K.J., Anjali Krishna, G., Varughese, J.K., Raghu, K.G., Philip, S., Divya, K.M., Augustine, M., and Mohanan, P.V., 2025, Unveiling the multifaceted bioactivity of copper(II)–Schiff base complexes: A comprehensive study of antioxidant, anti-bacterial, anti-inflammatory, enzyme inhibition and cytotoxic potentials with DFT insights, Dalton Trans., 54 (8), 3216–3234.‏

[14] Sonu, Thajudeen, K.Y., Parveen, B.R., Ahmed, M.M., Praveen, S., Alshehri, S.A., Singh, S., Naaz, A., Rani, S., Singh, N., Kumar, M., and Saini, R., 2025, Design, synthesis, and computational analysis of oxazine-based Schiff bases as prospective analgesic and anti-inflammatory agents, J. Mol. Struct., 1349, 143566.‏

[15] Iacopetta, D., Catalano, A., Ceramella, J., Mariconda, A., D’Amato, A., Checconi, P., Aquaro, S., Longo, P., and Sinicropi, M.S., 2025, Chitosan-based Schiff bases (CSBs) and their metal complexes: Promising antimicrobial agents, Molecules, 30 (2), 207.‏

[16] Ahmed Ali, M., Gad El-Karim, I.I., Behalo, M.S., and Negm, N.A., 2022, Synthesis and antimicrobial evaluation of some Schiff bases and their metal complexes against bacteria and fungi, Benha J. Appl. Sci., 7 (12), 109–124.‏

[17] Ngu, C.P., Sahu, R., Shah, K., Paliwal, D., Sah, A.K., and Prajapati, B.G., 2025, Recent development in synthesis and anticonvulsant activity of promising Schiff base derivatives, J. Heterocycl. Chem., 62 (10), 1264–1284.‏

[18] Mujeeb, S., Singh, K., Al-Zrkani, M.K., Al-Fahad, D., Hasan, S.M, Al Shouber, M., Ahmad, F., Hameed, H.N, Iqbal, D., and Kamal, M., 2025, Chroman-Schiff base derivatives as potential anti-tubercular agents: In silico studies, synthesis, and biological evaluation, Bioorg. Chem., 157, 108249.‏

[19] Lv, L., Zheng, T., Tang, L., Wang, Z., and Liu, W., 2025, Recent advances of Schiff base metal complexes as potential anticancer agents, Coord. Chem. Rev., 525, 216327.‏

[20] Felemban, M.F., Tayeb, F.J., Alqarni, A., Adnan Ashour, A., and Shafie, A., 2025, Recent advances in Schiff base coinage metal complexes as anticancer agents: A comprehensive review (2021–2025), Dyes Pigm., 237, 112710.‏

[21] Mubassir, M., Ahamad, N., and Kumar, A., 2025, Synthesis, characterization and pharmacological evaluation of some new Schiff base derivatives of 1H-indole-2-carbaldehyde, Adv. J. Chem., Sect. B, 7 (1), 53–65.‏

[22] Sakhare, D.T., 2025, Synthesis of Schiff bases ligand and biological activities of their transition metal complexes, J. Chem. Technol., 1 (4), 189–195.‏

[23] Amoko, J., 2025, Importance of Schiff bases and the metal complexes, J. Sci. Voc. Tech. Educ, 12 (2), 1–8.‏

[24] Verma, N., Shakir, S., Bano, K., and Mishra, B.N., 2025, “Medicinal Plants as Inspiring Source of Antimicrobial Agents” in Phytomolecules as a Source for Drug Discovery: Antimicrobials from Medicinal Plants, Eds. Upadhyay, H.C., Cambridge Scholars Publishing, Newcastle upon Tyne, UK, 134–150.

[25] Konaklieva, M.I., Plotkin, B.J., and Herbert, T., 2009, β-Lactams as neuroprotective agents, Anti-Infect. Agents Med. Chem., 8 (1), 28–35.‏

[26] Silveiro, C., Mortinho, D., Olivença, F., Mandal, M., Pires, D., Anes, E., and Catalão, M.J., 2025, Effects of CwlM, a peptidoglycan synthesis regulator, on beta-lactam resistance and host-pathogen interactions, BMC Microbiol., 26 (1), 21.‏

[27] Das, A., Yadav, R.N., and Banik, B.K., 2025, “Synthesis of pyrrole-substituted β-lactams by diverse catalytic methods” in Bioactive Four-Membered Heterocycles: Natural Products, Green Synthesis and Bioactivity, Eds. Khurana, J.M., and Banerjee, B., De Gruyter, Berlin, Germany, 97–114.‏

[28] Kapoor, V.K., 1988, Sulfadoxine, Anal. Profiles Drug Subst.,‏ 17, 571–605.

[29] Asagba, S.O., Eyaguobor, E.E., Emudainohwo, J.O.T., Njideaka, T.O., and Umeh, E.C., 2025, Synergistic and antagonistic effects of nickel and cadmium on oxidative stress and Ca²⁺-ATPase activity in rats, J. Basic Appl. Zool., 86 (1), 74.‏

[30] Wang, Y., Li, R., Xu, L., Xu, X., Pang, S., Zhang, X., Jiao, Q., Lv, X., Shen, Y., Zhao, Y., Liu, X., Yu, X., Zhou, B., and Wang, T., 2025, Biomimetic multinuclear nickel-polyphenol artificial enzyme with synergistic catalytic centers for broad-spectrum RONS scavenging: A therapeutic strategy against LPS-induced septic cardiomyopathy, Mol. Pharmaceutics, 22 (10), 5999–6013.‏

[31] Bhunya, D., Datta, R., Maity, R., Saha, A., Sen, S., Brandao, P., Pattanayak, S., Maity, T., Sarkar, K., and Samanta, B.C., 2025, Design and synthesis of bioactive Ru(II) complexes: Antibacterial activity, biocompatibility and biomolecular binding, RSC Adv., 15 (50), 42573–42587.‏

[32] Yadav, P., Berry, S., and Bhalla, A., 2025, Chemical methods for the construction of spirocyclic β-lactams and their biological importance, Synthesis, 57 (02), 251–274.‏

[33] Hatem Mohammed, Z., and Abd-alameer Jawad, S., 2025, Preparation, diagnosis and study of the effect of the biological activity of multi dentate azo-Schiff ligand and Cu(II), Zn(II) complexes, J. Kufa Chem. Sci., 4 (2), 615–630.‏

[34] Hussein, H.H., Al-Azawi, K.F., Hasoon, B.A., and El-Sayed, D.S., 2025, Advance screening of bis-azetidinone derivatives: Synthesis, spectroscopy, antioxidant and antimicrobial analysis with molecular docking assessment, Curr. Org. Synth., 22 (3), 396–409.‏

[35] Adeniyi, F.O., Wilson, F.O., and Oluboade, O.O., 2017, Phytochemicals, antioxidant potentials and 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity of Piper guineense (Schumach Thonn) seed, Afr. J. Plant Sci., 11 (4), 99–104.‏

[36] Qaisar, A., Khan, H., Habib, U., Rasool, S., Mumtaz, A., Mahmud, T., and Basra, M.A.R., 2025, Design, synthesis and analysis of Schiff based derivatives of sulfadoxine drug and their metal complexes, Results Chem., 17, 102560.‏‏

[37] Mondal, S., Mandal, S.M., Mondal, T.K., and Sinha, C., 2015, Structural characterization of new Schiff bases of sulfamethoxazole and sulfathiazole, their antibacterial activity and docking computation with DHPS protein structure, Spectrochim. Acta, Part A, 150, 268–279.‏

[38] Gomaa, M., Gad, W., Hussein, D., Pottoo, F.H., Tawfeeq, N., Alturki, M., Alfahad, D., Alanazi, R., Salama, I., Aziz, M., Zahra, A., and Hanafy, A., 2024, Sulfadiazine exerts potential anticancer effect in HepG2 and MCF7 cells by inhibiting TNFα, IL1b, COX-1, COX-2, 5-LOX gene expression: evidence from in vitro and computational studies, Pharmaceuticals, 17 (2), 189.‏

[39] Chu, F.L., and Yaylayan, V.A., 2008, Post-Schiff base chemistry of the Maillard reaction, Ann. N. Y. Acad. Sci., 1126(1), 30–37.

[40] Das, A., and Banik, B.K., 2025, Chemistry and Biology of Beta-lactams, CRC Press, Boca Raton, FL, US.‏

[41] Yakan, H., Çavuş, M.S., and Muğlu, H., 2026, Some new Schiff base derived thiosemicarbazones: Synthesis, spectroscopic characterization, and theoretical studies, Gümüşhane Üniv. J. Sci. Technol., 16 (1), 50–70.‏

[42] Knöpke, L.R., Nemati, N., Köckritz, A., Brückner, A., and Bentrup, U., 2010, Reaction monitoring of heterogeneously catalyzed hydrogenation of imines by coupled ATR‐FTIR, UV/vis, and Raman spectroscopy, ChemCatChem, 2 (3), 273–280.‏

[43] Kargar, H., Fallah-Mehrjardi, M., Zare-Mehrjardi, H.R., Dege, N., Ashfaq, M., Munawar, K.S., and Tahir, M.N., 2026, Copper(I) coordination polymers with bidentate Schiff base ligands: synthesis, spectral characterization, crystal structures, and electrochemical analysis, J. Iran. Chem. Soc., 23 (1), 18.‏

[44] Ghani, A.H.A., Mohammed, M.N., and Kadhim, M.I., 2025, Synthesis, characterization, molecular docking, and anticancer activity of new formazan derivatives, J. Med. Genet. Clin. Biol., 2 (9), 421–433.‏

[45] Al-Jumaili, M.H.A., Bakr, E.A., Huessien, M.A., Hamed, A.S., and Muhaidi, M.J., 2025, Development of heterocyclic-based anticancer agents: A comprehensive review, Heterocycl. Commun., 31 (1), 20220179.‏

[46] Rizwan, M., Khan, I., Sikandar Shah, S., Khan, A.H., Hajinur Hirad, A., Naz, S., Farid, A., Khan, T., and Hassan, S., 2025, Green synthesis of ZnO nanoparticles from Spirulina platensis: Antimicrobial and cytotoxic evaluation with molecular docking studies, ChemistryOpen, 15 (4), e202500515.‏

[47] Sangsri, R., Jongkon, N., Choowongkomon, K., Malaivijitnond, S., Day, N.P.J., Dondorp, A.M., and Imwong, M., 2025, Molecular analysis of DHFR and DHPS gene mutations in Plasmodium cynomolgi from humans and macaques in Southeast Asia, Parasite, 32, 64.‏

[48] Castro, L.H., and Sant'Anna, C.M.R., 2022, Molecular modeling techniques applied to the design of multitarget drugs: Methods and applications, Curr. Top. Med. Chem., 22 (5), 333–346.‏

DOI: https://doi.org/10.22146/ijc.115424