Applied Chemical Engineering

Synthesis and biological evaluation of some new tetrazole derivatives by using oxazine and thiazine compounds

Mohaymin. A. Abdul karim

Department of Basic Science, College Medicine, University of Ninevah, 41002, Mosul, Iraq

Salim J. mohammad

Department of Chemistry, College Science, University of Mosul, 41002, Mosul, Iraq

Mohanad. Y. Saleh

Department of Chemistry, College of Education for Pour Science, University of Mosul, 41002, Mosul, Iraq

Shakir M. Saied

College of pharmacy, Al Noor University, Al-Shallalat Road, 41003, Mosul, Iraq

DOI: https://doi.org/10.59429/ace.v8i3.5709

Keywords: chalcone; thiazine; oxazine; tetrazole; biological activity

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Abstract

This research included, in its first part, the preparation of the chalcone compound (M) from the reaction of para-nitroacetophenone with benzaldehyde in a basic medium of 40% aqueous sodium hydroxide solution. The second part of the research included the conversion of the compound (M) into the two compounds derived from 2-amino Thiazine (MS) and 2-aminooxazine (MO) by reacting the compound (M) with thiourea or urea, respectively, in a medium of alcoholic sodium hydroxide. In the third part of the research, the amine group in the two compounds (MS) and (MO) was exploited to prepare Schiff bases (MS_1-4) and   (MO_1-4) through the reaction of the two compounds (MS) and ((MO) with some benzaldehyde derivatives. In the last part of the research, the tetrazole compounds (MST_1-4) and (MOT_1-4) were prepared From the reaction of the prepared Schiff bases (MS_1-4) and (MO_1-4) with sodium azide in a medium of 1,4-dioxane, a test was conducted for the biological effectiveness of the prepared tetrazole compounds against Gram-positive and Gram-negative bacteria. In addition, some spectroscopic and physical measurements were performed of the prepared compounds.

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References

[1]. Maccari, R., & Ottanà, R. (2015). Targeting aldose reductase for the treatment of diabetes complications and inflammatory diseases: new insights and future directions. Journal of medicinal chemistry, 58(5), 2047-2067.‏

[2]. Chatzopoulou, M., Pegklidou, K., Papastavrou, N., & Demopoulos, V. J. (2013). Development of aldose reductase inhibitors for the treatment of inflammatory disorders. Expert opinion on drug discovery, 8(11), 1365-1380.‏

[3]. Liang, M., Li, X., Ouyang, X., Xie, H., & Chen, D. (2018). Antioxidant mechanisms of echinatin and licochalcone A. Molecules, 24(1), 3.‏

[4]. Sadeek, G. T., Saeed, Z. F., & Saleh, M. Y. (2023). Synthesis and Pharmacological Profile of Hydrazide Compounds. Research Journal of Pharmacy and Technology, 16(2), 975-982.‏

[5]. Shimokoriyama, M. (1962). Flavanones, chalcones and aurones. The Chemistry of Flavonoid Compounds. New York: The Macmillan Co.‏

[6]. Hamdoon, A. M., Al-Iraqi, M. A., & Saleh, M. Y. (2022). Synthesis of some multi-cyclic sulfhydryl donor compounds containing 1, 2-dithiol-3-thione moiety. Egyptian Journal of Chemistry, 65(3), 427-434.‏‏

[7]. Syahri, J., Nasution, H., Achromi, B., Bambang, P., & Yuanita, E. (2020). Novel aminoalkylated chalcone: Synthesis, biological evaluation, and docking simulation as potent antimalarial agents. Novel aminoalkylated chalcone: Synthesis, biological evaluation, and docking simulation as potent antimalarial agents, 10(6), 1-5.‏

[8]. Özdemir, A., Altıntop, M. D., Turan-Zitouni, G., Çiftçi, G. A., Ertorun, I., Alataş, Ö., & Kaplancıklı, Z. A. (2015). Synthesis and evaluation of new indole-based chalcones as potential antiinflammatory agents. European journal of medicinal chemistry, 89, 304-309.‏

[9]. Ganorkar, R. S., Ganorkar, R. P., & Parhate, V. V. (2013). Synthesis, Characterization and antibacterial activities of some new bromo/nitro 1, 3-thiazenes. Ras J chem, 6(1), 65-7.‏

[10]. Simerpreet, A. G., & Cannoo, S. D. (2013). Synthesis and biological evaluation of 1, 3-thiazines-a review. International Research Journal, 70-88.‏

[11]. Asif, M. (2015). Chemical and pharmacological potential of various substituted thiazine derivatives. Journal of Pharmaceutical and Applied Chemistry, 1(2), 1-16.‏

[12]. Saleh, M. Y., Sadeek, G. T., & Saied, S. M. (2023). Preparation and characterization of a dual acidic Ionic Liquid functionalized Graphene Oxide nanosheets as a Heterogeneous Catalyst for the Synthesis of pyrimido [4, 5-b] quinolines in water. Iranian Journal of Catalysis, 13(4), 499-516.‏

[13]. Sharma, P. K. (2016). Antifungal, Antibacterial and Antioxidant activities of substituted Morpholinylbenzothiazine. Der Pharmacia Lettre, 8(11), 140-142.‏

[14]. Kumar, G., Sharma, P. K., Sharma, S., & Singh, S. (2015). Synthesis and antimicrobial studies of fused heterocycles ‘pyrimidobenzothiazoles’. J Chem Pharm Res, 7, 710-714.‏

[15]. Barton, D. R. (1997). Oxidation of 2-phenylhydrazono-γ-butyrolactone: a novel ring expansion rearrangement leading to tetrahydro-1, 3-oxazine-2, 4-dione derivatives. Chemical Communications, (6), 571-572.‏

[16]. von Wittenau, M. S., & Els, H. (1961). The structure of indolmycin. Journal of the American Chemical Society, 83(22), 4678-4680.‏

[17]. Katritzky, A. R., & Lagowski, J. M. (1995). Heterocyclic chemistry. Synthesis, 1995(5), 605-606.‏

[18]. Beena, K. P., & Akelesh, T. (2013). Design, synthesis, characterization and evaluation of some 1, 3-oxazine derivatives as potent antimicrobial agents. Der pharmacia Lettre, 5(4), 257-260.‏

[19]. Saleh, M. Y., Aldulaimi, A. K. O., Saeed, S. M., & Adhab, A. H. (2024). Palladium fabricated on Fe3O4 as an organic-inorganic hybrid nanocatalyst for the Suzuki and Stille coupling reactions. Journal of Molecular Structure, 139597.

[20]. Le Bourdonnec, B., Meulon, E., Yous, S., Goossens, J. F., Houssin, R., & Hénichart, J. P. (2000). Synthesis and pharmacological evaluation of new pyrazolidine-3, 5-diones as AT1 angiotensin II receptor antagonists. Journal of medicinal chemistry, 43(14), 2685-2697.‏

[21]. Malik, M. A., Al-Thabaiti, S. A., & Malik, M. A. (2012). Synthesis, structure optimization and antifungal screening of novel tetrazole ring bearing acyl-hydrazones. International journal of molecular sciences, 13(9), 10880-10898.‏

[22]. Umarani, N., Ilango, K., & Singh, N. K. (2010). A facile design and efficient synthesis of schiff's bases of tetrazolo [1, 5-a] quinoxalines as potential anti-inflammatory and anti-microbial agents. Der Pharma Chemica, 2(1), 159-167.‏

[23]. Roh, J., Karabanovich, G., Vlčková, H., Carazo, A., Němeček, J., Sychra, P., ... & Hrabálek, A. (2017). Development of water-soluble 3, 5-dinitrophenyl tetrazole and oxadiazole antitubercular agents. Bioorganic & medicinal chemistry, 25(20), 5468-5476.‏

[24]. Ali, A. H., Saleh, M. Y., & Owaid, K. A. (2023). Mild Synthesis, Characterization, and Application of some Polythioester Polymers Catalyzed by Cetrimide Ionic Liquid as a Green and Eco-Friendly Phase-Transfer Catalyst. Iranian Journal of Catalysis, 13(1), 73-83.‏

[25]. Saleh, M. Y., Aldulaimi, A. K. O., Saeed, S. M., & Adhab, A. H. (2024). TiFe2O4@ SiO2–SO3H: A novel and effective catalyst for esterification reaction. Heliyon, 10(4).‏

[26]. Saleh, A., & Saleh, M. Y. (2022). Synthesis of heterocyclic compounds by cyclization of Schiff bases prepared from capric acid hydrazide and study of biological activity. Egyptian Journal of Chemistry, 65(12), 783-792.‏

[27]. Sultan, A. A., Saleh, M. Y., & Alkhalidi, E. F. A. (2022). Nano-Hydroxyapatite Remineralization of In-Situ Induced Enamel Caries. Journal of Nanostructures, 12(4), 1067-1074.‏

[28]. Saleh, M. Y., Al-barwari, A. S., & Ayoob, A. I. (2022). Synthesis of Some Novel 1, 8-Naphthyridine Chalcones as Antibacterial Agents. Journal of Nanostructures, 12(3), 598-606.‏

[29]. Hassan, E. M., Saleh, M. Y., Saied, S. M., & Kazemi, M. (2025). Magnetic-MOF Zinc nanocatalyst in DESs Solvent: A Sustainable Route for 2, 4-Disubstituted Quinoline Synthesis. Journal of Organometallic Chemistry, 123812.‏

[30]. Qusay Falih, I., AH Alobeady, M., Banoon, S. R., & Saleh, M. Y. (2021). Role of oxidized low-density lipoprotein in human diseases: a review. Journal of Chemical Health Risks, 11(Special Issue: Bioactive Compounds: Their Role in the Prevention and Treatment of Diseases), 71-83.‏

[31]. Sheet, S. H., Mahmod, R. B., Saeed, N. H., & Saied, S. M. (2024). Theoretical study for comparison of pka of a number of schiff bases by employing parameters derived from dft and mp2 method. New Materials, Compounds and Applications, 8(1), 94-108.‏

[32]. Moslem Ahmad, H., Yakdhan Saleh, M., & Aldahham, B. J. M. (2024). Dehydroepiandrosterone supplementation improves diminished ovarian reserve clinical and in silico studies. Steroids, 109490.

[33]. 1. Jawabrah Al-Hourani, B., Sharma, S. K., Kaur, J., & Wuest, F. (2015). Synthesis, bioassay studies, and molecular docking of novel 5-substituted 1H tetrazoles as cyclooxygenase-2 (COX-2) inhibitors. Medicinal Chemistry Research, 24(1), 78–85. https://doi.org/10.1007/s00044-014-1102-1

[34]. Altıntop, M. D., Sever, B., Temel, H. E., Kaplancıklı, Z. A., & Özdemir, A. (2022). Design, synthesis and in-vitro COX inhibitory profiles of a new series of tetrazole-based hydrazones. European Journal of Life Sciences, 1(1), 20–27. https://doi.org/10.55971/EJLS.1095818