Microbiology, Metabolites and Biotechnology

Microbiology, Metabolites and Biotechnology

6-Amino-4H-pyran derivatives as potential anti-microbial and amyloid aggregation inhibitory agents

Document Type : Research Paper

Authors
1 Department of Biology, Ra. C., Islamic Azad University, Rasht, Iran
2 Department of Chemistry, Ra. C., Islamic Azad University, Rasht, Iran
Abstract
Pyran and its derivatives are an important group of heterocyclic compounds. These compounds are used in chemistry and pharmacy. This study investigates the anti-microbial and anti-Alzheimer's effects of 6-amino-4H-pyran derivatives. 6-amino-4H-pyran derivatives were produced from ethyl acetoacetate, with benzaldehydes and malononitrile in the presence of nano–MgO in water at 80 ºC by remarkable efficiency. MIC, MBC, and disc diffusion methods were performed to evaluate the antibacterial effects of five 6-amino-4H-pyran derivatives. The Congo red uptake method was used to determine the degree of inhibition of amyloid fibril production from Bovine serum albumin. For all five 6-amino-4H-pyran derivatives, the minimum inhibitory concentration for both Escherichia coli (PTCC 13301) and Staphylococcus aureus (PTCC 1112) was observed in a 1:8 (v/v) dilution rate (125 μg/ml), and the minimum bactericidal concentration in gram-negative and gram-positive bacteria was in a 1:4 (v/v) dilution rate (250 μg/ml). Also, the best inhibitory properties for amyloid fibrils were seen at 12%, 4%, 8%, 16%, and 12% (w/v) solutions for 4a–4e compounds, respectively. The most significant reduction in the production of amyloid fibrils was observed for benzyl 6-amino-4-(3-chlorophenyl)-5-cyano-2-methyl-4H-pyran- 3-carboxylate (4d). The identified antimicrobial activity and inhibition of amyloid fibril production by 6-amino-4H-pyran derivatives indicate a potential area for future therapeutic development. However, comprehensive studies are needed to establish their efficacy in addressing complications of infectious diseases and Alzheimer’s.
Keywords
Subjects

Arasteh, A., Habibi-Rezaei, M., Ebrahim-Habibi, A., & Moosavi-Movahedi, A. A. (2012). Response surface methodology for optimizing the bovine serum albumin fibrillation. The Protein Journal, 31(6), 457–465. 
https://doi.org/10.1007/s10930-012-9422-9
Balouiri, M., Sadiki, M., & Ibnsouda, S. K. (2016). Methods for in vitro evaluating antimicrobial activity: A review. Journal of Pharmaceutical Analysis, 6(2), 71–79. 
https://doi.org/10.1016/j.jpha.2015.11.005
Breijyeh, Z., & Karaman, R. (2020). Comprehensive review on Alzheimer’s disease: Causes and treatment. Molecules, 25(24), Article 5789. 
https://doi.org/10.3390/molecules25245789
El-Kady, I. A., Zohri, A. N. A., & Hamed, S. R. (2014). Kojic acid production from agro-industrial by-products using fungi. Biotechnology Research International, 2014. 
https://doi.org/10.1155/2014/642385
Freyssin, A., Page, G., Fauconneau, B., & Bilan, A. R. (2018). Natural polyphenols effects on protein aggregates in Alzheimer's and Parkinson's prion-like diseases. Neural Regeneration Research, 13(6), 955. 
https://doi.org/10.4103/1673-5374.233432
Hampel, H., Vassar, R., De Strooper, B., Hardy, J., Willem, M., Singh, N., et al. (2021). The β-secretase BACE1 in Alzheimer’s disease. Biological Psychiatry, 89(8), 745–756.
Huang, L.-K., Chao, S.-P., & Hu, C.-J. (2020). Clinical trials of new drugs for Alzheimer disease. Journal of Biomedical Science, 27(1), 1–13. 
https://doi.org/10.1186/s12929-023-00976-6
Khalaji, N., Sarkissian, J., Chavushyan, V., & Sarkisian, V. (2017). Protective effects of proline–rich peptide in a rat model of Alzheimer disease: An electrophysiological study. Basic and Clinical Neuroscience, 8(1), 5. 
https://doi.org/10.1155/2017/3948685
Khazaey, M. R., Habibi-Rezaei, M., Safarian, S., Karami, Z., & Sabouni, F. (2010). AGE proteins as a causative factor in Alzheimer's disease. Iranian Journal of Pharmaceutical Research, Supplement(1), 79–79.
Khonacha, S. E., Janahmadi, M., & Motamedi, F. (2019). Kisspeptin-13 improves spatial memory consolidation and retrieval against amyloid-β pathology. Iranian Journal of Pharmaceutical Research: IJPR, 18(Suppl 1), 169. 
https://doi.org/10.1016/j.neuroscience.2019.07.014
Kövari, E., Herrmann, F. R., Hof, P. R., & Bouras, C. (2013). The relationship between cerebral amyloid angiopathy and cortical microinfarcts in brain ageing and Alzheimer's disease. Neuropathology and Applied Neurobiology, 39(5), 498–509. 
https://doi.org/10.1111/nan.12003
Kumar, D., Sharma, P., Singh, H., Nepali, K., Gupta, G. K., Jain, S. K., et al. (2017). The value of pyrans as anticancer scaffolds in medicinal chemistry. RSC Advances, 7(59), 36977–36999. 
https://doi.org/10.1039/C7RA07845A
Kumar, K. A., Renuka, N., Kumar, G. V., & Lokeshwari, D. M. (2015). Pyrans: Heterocycles of chemical and biological interest. Journal of Chemical and Pharmaceutical Research, 7(11), 693–700.
Ma, C., Hong, F., & Yang, S. (2022). Amyloidosis in Alzheimer’s disease: Pathogeny, etiology, and related therapeutic directions. Molecules, 27(4), Article 1210. 
https://doi.org/10.3390/molecules27041210
Mahdavi, S. M., Habibi, A., Dolati, H., Shahcheragh, S. M., Sardari, S., & Azerang, P. (2018). Synthesis and antimicrobial evaluation of 4H-pyrans and schiff bases fused 4H-pyran derivatives as inhibitors of Mycobacterium bovis (BCG). Iranian Journal of Pharmaceutical Research: IJPR, 17(4), 1229.
Omar, S. H., Scott, C. J., Hamlin, A. S., & Obied, H. K. (2017). The protective role of plant biophenols in mechanisms of Alzheimer's disease. The Journal of Nutritional Biochemistry, 47, 1–20. 
https://doi.org/10.1016/j.jnutbio.2017.02.016
Ow, S.-Y., & Dunstan, D. E. (2014). A brief overview of amyloids and Alzheimer's disease. Protein Science, 23(10), 1315–1331. 
https://doi.org/10.1002/pro.2524
Perluigi, M., Di Domenico, F., & Butterfield, D. A. (2024). Oxidative damage in neurodegeneration: Roles in the pathogenesis and progression of Alzheimer disease. Physiological Reviews, 104(1), 103–197. 
https://doi.org/10.1016/j.redox.2023.103057
Pourshojaei, Y., Abiri, A., Eskandari, R., Dourandish, F., Eskandari, K., & Asadipour, A. (2019). Synthesis, biological evaluation, and computational studies of novel fused six-membered O-containing heterocycles as potential acetylcholinesterase inhibitors. Computational Biology and Chemistry, 80, 249–258. 
https://doi.org/10.1016/j.ejmech.2019.04.005
Rajmohan, R., & Reddy, P. H. (2017). Amyloid-beta and phosphorylated tau accumulations cause abnormalities at synapses of Alzheimer’s disease neurons. Journal of Alzheimer's Disease, 57(4), 975–999. 
https://doi.org/10.3233/JAD-160612
Sharma, S., Brahmachari, G., Banerjee, B., Kant, R., & Gupta, V. K. (2015). X-ray studies of methyl 6-amino-5-cyano-2-methyl-4-(3-nitrophenyl)-4H-pyran-3-carboxylate. European Chemical Bulletin, 4(5), 230–233. 
https://doi.org/10.1134/S1063774515050236
Sojoudi, M., & Mokhtary, M. (2018). Efficient one-pot synthesis of 6-amino-4-aryl-5-cyano-2-methyl-4H-pyran-3-carboxylates catalyzed by nano MgO in water. Quarterly Journal of Iranian Chemical Communication, 6(2), 125–133. 
https://doi.org/10.22034/IJC.2018.55797.1306
Winblad, B., Amouyel, P., Andrieu, S., Ballard, C., Brayne, C., Brodaty, H., et al. (2016). Defeating Alzheimer's disease and other dementias: A priority for European science and society. The Lancet Neurology, 15(5), 455–532. 
https://doi.org/10.1016/S1474-4422(16)30055-9