https://doi.org/10.65770/FBAU8087
ABSTRACT
By using Claisen Schmidt condensation method, various substituted acetophenones were reacted with 4-hydroxy-3,5-dimethoxybenzaldehyde to produce different chalcones (3a-k). The synthesis of substituted 2-amino-4-(4-hydroxy-3,5-dimethoxyphenyl)-nicotinonitrile (KMC-1 to KMC-11) was accomplished by condensing substituted chalcones (3a-k) with malononitrile and ammonium acetate in different solvents like methanol, ethanol, and DMSO, respectively. Cyanopyridines play an vital role in our life due to their biological significance in the struggle pathogens. All synthesized compounds underwent evaluation for their antibacterial properties. Compared to Tetracycline, the tested antibacterial compound showed significantly lower or moderate efficacy against both Gram-positive and Gram-negative bacteria. The most active compound was KMC-1 and KMC-5 against Bacillus cereus, with a 12.0-13.0 mm zone of inhibition (For Tetracycline, 21 mm). SwissADME assesses pharmacokinetic behavior and drug-likeness based on molecular structure, assisting in the prediction of compounds’ suitability as oral medication candidates. The majority of KMC compounds exhibit high GI absorption, including KMC-1, KMC-2, KMC-3, KMC-4, KMC-7, KMC-8, KMC-9, KMC-10, and KMC-11. Good oral bioavailability and effective intestine absorption are indicated by high GI absorption. TPSA values for the majority of substances range from 101 to 147 Ų. It is not anticipated that any will pass through the BBB.
References
- Shalaby, Mona A., Sameh A. Rizk, and Asmaa M. Fahim. Synthesis, reactions and application of chalcones: a systematic review. Organic & biomolecular chemistry26 (2023): 5317-5346. https://doi.org/10.1039/D3OB00792H
- Rajendran, Gayathri, et al. Chalcone: A promising bioactive scaffold in medicinal chemistry. Pharmaceuticals10 (2022): 1250.https://doi.org/10.3390/ph15101250
- Salehi, Bahare, et al. Pharmacological properties of chalcones: a review of preclinical including molecular mechanisms and clinical evidence. Frontiers in pharmacology11 (2021): 592654. https://doi.org/10.3389/fphar.2020.592654
- Gaur, Rashmi, et al. Synthesis of a series of novel dihydroartemisinin monomers and dimers containing chalcone as a linker and their anticancer activity. European journal of medicinal chemistry122 (2016): 232-246. https://doi.org/10.1016/j.ejmech.2016.06.035
- Subhashini, N. J. P., et al. Synthesis, characterization, and antimicrobial activity of novel (E)-1-(aryl)-3-{3, 5-dimethoxy-4-[(1-(aryl)-1 H-1, 2, 3-triazol-4-yl) methoxy] phenyl} prop-2-en-1-ones. Russian Journal of General Chemistry6 (2016): 1405-1411. https://doi.org/10.1134/S107036321606027X
- Bianco, Armandodoriano, Claudia Cavarischia, and Marcella Guiso. The Heck coupling reaction using aryl vinyl ketones: synthesis of flavonoids. European Journal of Organic Chemistry13 (2004): 2894-2898.https://doi.org/10.1002/ejoc.200400032
- Bano, Sameena, et al. Synthesis and biological evaluation of some new 2-pyrazolines bearing benzene sulfonamide moiety as potential anti-inflammatory and anti-cancer agents. European journal of medicinal chemistry12 (2011): 5763-5768. https://doi.org/10.1016/j.ejmech.2011.08.015
- Nayak, Sabita, et al. Recent advances of organocatalytic enantioselective Michael-addition to chalcone. Research on Chemical Intermediates4 (2016): 2731-2747. https://doi.org/10.1007/s11164-015-2193-0
- Nguyen, Khang X., et al. Trisulfur-Radical-anion-triggered C (sp2)–H amination of electron-deficient alkenes. Organic letters24 (2020): 9751-9756. https://doi.org/10.1021/acs.orglett.0c03846
- Mohamed, Salwa F., et al. Synthesis, anticancer activity, pharmacokinetics, and docking study of some new heterocycles linked indole moiety. Polycyclic Aromatic Compounds10 (2023): 8752-8771. https://doi.org/10.1080/10406638.2022.2151475
- El-Naggar, Mohamed, Huda RM Rashdan, and Aboubakr H. Abdelmonsef. Cyclization of chalcone derivatives: design, synthesis, in silico docking study, and biological evaluation of new quinazolin-2, 4-diones incorporating five-, six-, and seven-membered ring moieties as potent antibacterial inhibitors. ACS omega30 (2023): 27216-27230., https://doi.org/10.1021/acsomega.3c02478
- Insuasty, Braulio, et al. An efficient synthesis of new caffeine-based chalcones, pyrazolines and pyrazolo [3, 4-b][1, 4] diazepines as potential antimalarial, antitrypanosomal and antileishmanial agents. European Journal of Medicinal Chemistry93 (2015): 401-413.https://doi.org/10.1016/j.ejmech.2015.02.040
- Zhang, Yuanqing, et al. CuO-promoted construction of N-2-aryl-substituted-1, 2, 3-triazoles via azide-chalcone oxidative cycloaddition and post-triazole arylation. Organic Letters1 (2012): 26-29.https://doi.org/10.1021/ol202718d
- Singh, Nimisha, S. K. Pandey, and Rama P. Tripathi. Regioselective [3+ 2] cycloaddition of chalcones with a sugar azide: easy access to 1-(5-deoxy-d-xylofuranos-5-yl)-4, 5-disubstituted-1H-1, 2, 3-triazoles. Carbohydrate research12 (2010): 1641-1648.https://doi.org/10.1016/j.carres.2010.04.019
- Manna, F., et al. Anti-inflammatory, analgesic and antipyretic 4, 6-disubstituted 3-cyanopyridine-2-ones and 3-cyano-2-aminopyridines. European journal of medicinal chemistry6 (1992): 627-632.https://doi.org/10.1016/0223-5234(92)90141-M
- Yadav, Sumit, et al. A review on targets and synthesis methods of pyridine compounds for anti-convulsant, anti-depressant actions. Journal of Chemical Reviews6 (2024): 403-432. https://doi.org/10.48309/jcr.2024.462308.1337
- Dawood, Dina, et al. Synthesis and Molecular Modeling Study of New Pyrimidine-Based Derivatives as Anticonvulsant Agents. Egyptian Journal of Chemistry1 (2025): 109-122. https://doi.org/10.21608/ejchem.2024.269889.9339
- Amr, Abd El‐Galil E., Hayam H. Sayed, and Mohamed M. Abdulla. Synthesis and reactions of some new substituted pyridine and pyrimidine derivatives as analgesic, anticonvulsant and antiparkinsonian agents. Archiv der Pharmazie: An International Journal Pharmaceutical and Medicinal Chemistry9 (2005): 433-440. https://doi.org/10.1002/ardp.200500982
- Mohammed, Mariam M., Hiba H. Ibraheem, and Amal A. Hussein. Synthesis and Biological evaluation of Novel Nicotinonitrile derivatives derived from N-Substituted Coumarinyl Chalcones. Journal of Physics: Conference Series. Vol. 1795. No. 1. IOP Publishing, 2021. https://doi:10.1088/1742-6596/1795/1/012022
- Alazawi, S. M., et al. “Synthesis, Spectral and Biological Studies of New 2-amino-3-cyanopyridine Derivatives and Their Transition Metals Complexes.” Egyptian Journal of Chemistry6 (2021): 2937-2944. https://doi.org/10.21608/ejchem.2021.55730.3173
- Ismail, Magda MF, et al. Apoptosis: A target for anticancer therapy with novel cyanopyridines. Bioorganic Chemistry94 (2020): 103481. https://doi.org/10.1016/j.bioorg.2019.103481
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