Synthesis, Characterization, and Antimicrobial Activity of Spiro Heterocyclic Compounds from Statin

Zubaida Amir Al-Heety ¹, Ali Kareem Al-Nasseri ^2*

The study elucidated the synthesis, structural characterization, and diverse biological activities of spiro heterocyclic compounds.

Abstract

Background: Heterocyclic compounds, including spiro compounds, constitute a diverse family of chemical substances with unique properties that make them relevant in biology, materials research, and medicinal chemistry. Methods: In this study, a series of spiro heterocyclic compounds were synthesized from isatin and primary derivatives using various reagents. The compounds were characterized using various analytical techniques such as FT-IR, NMR spectroscopy, and mass spectrometry. Additionally, the electronic properties and geometric optimization of the synthesized compounds were investigated using computational methods based on DFT. Results: The synthesis of spiro heterocyclic compounds yielded moderate to good yields, which were confirmed by spectroscopic data. Biological evaluation of some synthesized compounds revealed antibacterial and antifungal activities against various strains of bacteria and fungi. Computational analysis provided insights into the geometric optimization and electronic properties of the compounds, shedding light on their stability and reactivity. Conclusion: The synthesis and characterization of spiro heterocyclic compounds, along with their biological evaluation and computational analysis, provide valuable information about their potential applications in various fields. The study demonstrates the versatility of spiro compounds and highlights their importance in medicinal chemistry and materials science. Further research on the synthesis and properties of spiro compounds could lead to the development of novel drugs and functional materials with enhanced efficacy and performance.

Keywords: Spiro compounds, Heterocyclic compounds, Synthesis, Density functional theory, Antibacterial, Antifungal.

References

Abdella, A. M., Abdelmoniem, A. M., Abdelhamid, I. A., & Elwahy, A. H. M. (2020). Synthesis of heterocyclic compounds via Michael and Hantzsch reactions. Journal of Heterocyclic Chemistry, 57(4), 1476–1523. doi:10.1002/jhet.3883.

Abdella, A. M., Abdelmoniem, A. M., Abdelhamid, I. A., & Elwahy, A. H. M. (2020). Synthesis of heterocyclic compounds via Michael and Hantzsch reactions. Journal of Heterocyclic Chemistry, 57(4), 1476–1523. https://doi.org/10.1002/jhet.3883

Abeer Hussein Ali, and Mukhlif Mohsin Slaihimb, (2023),  Design, Synthesis, And Characterization Of New Schiff Bases For 3-Amino-1,2,4-Triazole-5-Thiolate Salt, Bearing Morpholine Ring And Biological Evaluation As Antibacterial Agents, Journal of Angiotherpay, 7(1), 1-9, 7333

Adlu, M., & Yavari, I. (2023). One-pot, mild and efficient multicomponent synthesis of novel various spiro-nitrogen heterocycle compounds. Bull. Chem. Soc. Ethiop., 37(1), 115–122.

Adlu, M., & Yavari, I. (2023). One-pot, mild and efficient multicomponent synthesis of novel various spiro-nitrogen heterocycle compounds. Bull. Chem. Soc. Ethiop., 37(1), 115–122.

Adlu, M., & Yavari, I. (2023). One-pot, mild and efficient multicomponent synthesis of novel various spiro-nitrogen heterocycle compounds. Bulletin of the Chemical Society of Ethiopia, 37(1), 115–122.

Al-Naseeri, A. K. A., Saleh, H. K., & Jassim, I. K. (2021). Synthesis, characterization, and theoretical study of new schiff bases from (S)-2-amino-3-(3,4-dihydroxyphenyl)-2-methyl propanoic acid as initial material of 1,3-oxazepine-1,5-dione. Int. J. Drug Deliv. Technol., 11(2), 258–264. doi:10.25258/ijddt.11.2.3.

Al-Naseeri, A. K. A., Saleh, H. K., & Jassim, I. K. (2021). Synthesis, characterization, and theoretical study of new schiff bases from (S)-2-amino-3-(3,4-dihydroxyphenyl)-2-methyl propanoic acid as initial material of 1,3-oxazepine-1,5-dione. International Journal of Drug Delivery Technology, 11(2), 258–264. https://doi.org/10.25258/ijddt.11.2.3

Aytac, S., Gundogdu, O., Bingol, Z., & Gulcin, I. (2023). Synthesis of Schiff Bases Containing Phenol Rings and Investigation of Their Antioxidant Capacity, Anticholinesterase, Butyrylcholinesterase, and Carbonic Anhydrase Inhibition Properties. Pharmaceutics, 15(3), 779. doi:10.3390/pharmaceutics15030779.

Aytac, S., Gundogdu, O., Bingol, Z., & Gulcin, I. (2023). Synthesis of Schiff Bases Containing Phenol Rings and Investigation of Their Antioxidant Capacity, Anticholinesterase, Butyrylcholinesterase, and Carbonic Anhydrase Inhibition Properties. Pharmaceutics, 15(3), 779. https://doi.org/10.3390/pharmaceutics15030779

Bashar, B. S., et al. (2022). Application of novel Fe3O4/Zn-metal organic framework magnetic nanostructures as an antimicrobial agent and magnetic nanocatalyst in the synthesis of heterocyclic compounds. Front. Chem., 10, 1–17. doi:10.3389/fchem.2022.1014731.

Bashar, B. S., et al. (2022). Application of novel Fe3O4/Zn-metal organic framework magnetic nanostructures as an antimicrobial agent and magnetic nanocatalyst in the synthesis of heterocyclic compounds. Frontiers in Chemistry, 10. https://doi.org/10.3389/fchem.2022.1014731

Brandl, M. T. (2006). Fitness of human enteric pathogens on plants and implications for food safety. Annu. Rev. Phytopathol., 44, 367–392. doi:10.1146/annurev.phyto.44.070505.143359.

Brandl, M. T. (2006). Fitness of human enteric pathogens on plants and implications for food safety. Annual Review of Phytopathology, 44, 367–392. https://doi.org/10.1146/annurev.phyto.44.070505.143359

Canneaux, S., Bohr, F., & Henon, E. (2014). KiSThelP: a program to predict thermodynamic properties and rate constants from quantum chemistry results. J. Comput. Chem., 35(1), 82–93.

Canneaux, S., Bohr, F., & Henon, E. (2014). KiSThelP: A program to predict thermodynamic properties and rate constants from quantum chemistry results. Journal of Computational Chemistry, 35(1), 82–93.

Dabhi, R. A., Dhaduk, M. P., Bhatt, V. D., & Bhatt, B. S. (2022). Synthetic approach toward spiro quinoxaline-β-lactam based heterocyclic compounds: Spectral characterization, SAR, pharmacokinetic and biomolecular interaction studies. Journal of Biomolecular Structure and Dynamics. doi: 10.1080/07391102.2022.2086176.

Dabhi, R. A., Dhaduk, M. P., Bhatt, V. D., & Bhatt, B. S. (2022). Synthetic approach toward spiro quinoxaline-β-lactam based heterocyclic compounds: Spectral characterization, SAR, pharmacokinetic and biomolecular interaction studies. Journal of Biomolecular Structure and Dynamics. doi:10.1080/07391102.2022.2086176

Dabhi, R. A., Dhaduk, M. P., Bhatt, V. D., & Bhatt, B. S. (2022). Synthetic approach toward spiro quinoxaline-β-lactam based heterocyclic compounds: Spectral characterization, SAR, pharmacokinetic and biomolecular interaction studies. Journal of Biomolecular Structure and Dynamics. https://doi.org/10.1080/07391102.2022.2086176

Farah M. Muhammad, Bushra A. Khairallah, K. A. Albadrany. (2024). Synthesis, characterization and Antibacterial Evaluation of Novel 1,3-Oxazepine Derivatives Using A Cycloaddition Approach, Journal of Angiotherapy, 8(3), 1-5, 9506

Hussein Abdulkadhim Hasan, Saad M. Mahdi, Hanaa Addai Ali. (2024). Synthesis, Charecterization, Antibacterial and Cytotoxicity of Novel Metal Complexes Derived from Azomethine Ligand (Bis Azo-Schiff Base) In Vitro and In Silico, Journal of Angiotherapy, 8(3), 1-12, 9531

Izsák, R., et al. (2023). Quantum computing in pharma: A multilayer embedding approach for near future applications. J. Comput. Chem., 44(3), 406–421.

Izsák, R., et al. (2023). Quantum computing in pharma: A multilayer embedding approach for near future applications. J. Comput. Chem., 44(3), 406–421.

Izsák, R., et al. (2023). Quantum computing in pharma: A multilayer embedding approach for near future applications. Journal of Computational Chemistry, 44(3), 406–421.

Kareem, A., & Humadi, A. (2009). The cemecales.

Kareem, A., & Humadi, A. (2009). The cemecales.

Kareem, A., & Humadi, A. (2009). The cemecales.

Kumar, T., Satam, N., & Namboothiri, I. N. N. (2016). Hauser–Kraus Annulation of Phthalides with Nitroalkenes for the Synthesis of Fused and Spiro Heterocycles. European J. Org. Chem., 2016(20), 3316–3321.

Kumar, T., Satam, N., & Namboothiri, I. N. N. (2016). Hauser–Kraus Annulation of Phthalides with Nitroalkenes for the Synthesis of Fused and Spiro Heterocycles. European J. Org. Chem., 2016(20), 3316–3321.

Kumar, T., Satam, N., & Namboothiri, I. N. N. (2016). Hauser–Kraus Annulation of Phthalides with Nitroalkenes for the Synthesis of Fused and Spiro Heterocycles. European Journal of Organic Chemistry, 2016(20), 3316–3321.

Lamont, R. J., Hajishengallis, G. N., & Jenkinson, H. F. (2014). Oral microbiology and immunology. (2nd ed.). ASM press.

Lamont, R. J., Hajishengallis, G. N., & Jenkinson, H. F. (2014). Oral microbiology and immunology (2nd ed.). ASM Press.

Lopes Lima, K. A., & Ribeiro, L. A. (2023). A DFT study on the mechanical, electronic, thermodynamic, and optical properties of GaN and AlN counterparts of biphenylene network. Mater. Today Commun., 37, 1–22. doi: 10.1016/j.mtcomm.2023.107183.

Lopes Lima, K. A., & Ribeiro, L. A. (2023). A DFT study on the mechanical, electronic, thermodynamic, and optical properties of GaN and AlN counterparts of biphenylene network. Mater. Today Commun., 37, 1–22. doi:10.1016/j.mtcomm.2023.107183.

Lopes Lima, K. A., & Ribeiro, L. A. (2023). A DFT study on the mechanical, electronic, thermodynamic, and optical properties of GaN and AlN counterparts of biphenylene network. Materials Today Communications, 37, 1–22. https://doi.org/10.1016/j.mtcomm.2023.107183

Marsh, P. D., Lewis, M. A. O., Williams, D. W., & Martin, M. V. (2009). Oral microbiology E-book. Elsevier health sciences.

Marsh, P. D., Lewis, M. A. O., Williams, D. W., & Martin, M. V. (2009). Oral microbiology E-book. Elsevier Health Sciences.

Martínez, J., et al. (2023). Computational Studies of Aflatoxin B1 (AFB1): A Review. Toxins (Basel), 15(2). doi: 10.3390/toxins15020135.

Martínez, J., et al. (2023). Computational Studies of Aflatoxin B1 (AFB1): A Review. Toxins (Basel)., 15(2). doi:10.3390/toxins15020135.

Martínez, J., et al. (2023). Computational Studies of Aflatoxin B1 (AFB1): A Review. Toxins (Basel), 15(2). https://doi.org/10.3390/toxins15020135

Pederson, R., Kalita, B., & Burke, K. (2022). Machine learning and density functional theory. Nat. Rev. Phys., 4(6), 357–358.

Pederson, R., Kalita, B., & Burke, K. (2022). Machine learning and density functional theory. Nat. Rev. Phys., 4(6), 357–358.

Pederson, R., Kalita, B., & Burke, K. (2022). Machine learning and density functional theory. Nature Reviews Physics, 4(6), 357–358.

Raju, R., Raghunathan, R., Arumugam, N., Almansour, A. I., & Kumar, R. S. (2020). Regio-and stereoselective synthesis of novel β-lactam engrafted spiroheterocyclic hybrids via one-pot three component cycloaddition strategy. Tetrahedron Lett., 61(52), 152661.

Raju, R., Raghunathan, R., Arumugam, N., Almansour, A. I., & Kumar, R. S. (2020). Regio-and stereoselective synthesis of novel β-lactam engrafted spiroheterocyclic hybrids via one-pot three component cycloaddition strategy. Tetrahedron Letters, 61(52), 152661.

Shaima H. Abdullah, Mahmoud M. Salih, Khalid, A. Al-Badrany. (2024). Synthesis, characterization and Antibacterial Evaluation of Novel Thiazolidine Derivatives, Journal of Angiotherapy, 8(3), 1-6, 9501

Singh, G. S., & Desta, Z. Y. (2012). Isatins as privileged molecules in design and synthesis of spiro-fused cyclic frameworks. Chem. Rev., 112(11), 6104–6155. doi: 10.1021/cr300135y.

Singh, G. S., & Desta, Z. Y. (2012). Isatins as privileged molecules in design and synthesis of spiro-fused cyclic frameworks. Chem. Rev., 112(11), 6104–6155. doi:10.1021/cr300135y.

Singh, G. S., & Desta, Z. Y. (2012). Isatins as privileged molecules in design and synthesis of spiro-fused cyclic frameworks. Chemical Reviews, 112(11), 6104–6155. https://doi.org/10.1021/cr300135y

Villarreal, Y., Insuasty, B., Abonia, R., Ortiz, A., Romo, P., & Quiroga, J. (2021). Three-component one-pot synthesis of new spiro[indoline-pyrrolidine] derivatives mediated by 1,3-dipolar reaction and DFT analysis. Monatshefte fur Chemie, 152(5), 497–506. doi:10.1007/s00706-021-02765-z.

Villarreal, Y., Insuasty, B., Abonia, R., Ortiz, A., Romo, P., & Quiroga, J. (2021). Three-component one-pot synthesis of new spiro[indoline-pyrrolidine] derivatives mediated by 1,3-dipolar reaction and DFT analysis. Monatshefte fur Chemie, 152(5), 497–506. https://doi.org/10.1007/s00706-021-02765-z

Yang, L., Liu, Y., Sternberg, C., & Molin, S. (2010). Evaluation of enoyl-acyl carrier protein reductase inhibitors as Pseudomonas aeruginosa quorum-quenching reagents. Molecules, 15(2), 780–792. doi:10.3390/molecules15020780.

Yang, L., Liu, Y., Sternberg, C., & Molin, S. (2010). Evaluation of enoyl-acyl carrier protein reductase inhibitors as Pseudomonas aeruginosa quorum-quenching reagents. Molecules, 15(2), 780–792. https://doi.org/10.3390/molecules15020780

Yuan, Y., et al. (2020). Synthesis of Spiro[5.n (n=6–8)]heterocycles through Successive Ring-Expansion/Indole C-2 Functionalization. Adv. Synth. Catal., 362(6), 1298–1302. doi: 10.1002/adsc.201901631.

Yuan, Y., et al. (2020). Synthesis of Spiro[5.n (n=6–8)]heterocycles through Successive Ring-Expansion/Indole C-2 Functionalization. Adv. Synth. Catal., 362(6), 1298–1302. doi:10.1002/adsc.201901631.

Yuan, Y., et al. (2020). Synthesis of Spiro[5.n (n=6–8)]heterocycles through Successive Ring-Expansion/Indole C-2 Functionalization. Advanced Synthesis & Catalysis, 362(6), 1298–1302.