Design, Molecular Docking, Synthesis of Aromatic Amino Acids Linked to Cephalexin.

Authors

  • Yasir F. Muhsin Department of Pharmacy, Ashur University College, Baghdad-Iraq
  • Shakir M. Alwan Department of Pharmacy, Al-Farabi University College, Baghdad-Iraq
  • Ayad Kareem Khan Department of Pharmaceutical Chemistry, College of Pharmacy, Mustansiriyah University, Baghdad-Iraq.

DOI:

https://doi.org/10.32947/ajps.v21i3.794

Abstract

Infections caused by bacteria have a significant impact on public health. Chemical synthesis of new derivatives of cephalexin inked to amino acid (tryptophan or histidine) through an amide bond at the acyl side chain is achieved. This is a new

approach of incorporating, tryptophan and histidine into the the primary amino group of cephalexin, in order to provide a bulky group very close to the β-lactam ring. This chemical addition act as isosteric group to the alkoximino that protect beta lactam ring from bacterial beta lactamase enzyme. The new derivatives may show resistance to β-lactamases, improve activity and pharmacokinetic properties and may give new life for old drugs that are susceptible to hydrolysis by most β-lactamases. The chemical structures of these derivatives were confirmed by: FTIR, 1H-NMR spectroscopy, elemental micro analysis and some physical properties. Molecular docking on serine beta lactamase and prediction of ADME parameters were recorded using GOLD suite and Swiss ADME software respectively. Docking scores of the new derivatives of Cephalexin on β-lactamases were higher than those of Cephalexin, which may indicate better activity

References

- Gary, A. Kelvin, T. Patton, E. Synthesis and biological evaluation of some novel schiff bases of cephalexin. Int. J.Pharmaceut. 2004, 7, 703.

- Bell, B. Schellevis, F. Stobberingh, E. Goossens, H. Pringle, M. A systematic review and meta-analysis of the effects of antibiotic consumption on antibiotic resistance. BMC Infect Dis. 2014, 14, 13. DOI: https://doi.org/10.1186/1471-2334-14-13

- Najib, N. Suleiman, M. High performance liquid chromatographic analysis of cephalexin in serum and urine. J.Clin.Pharm. &Therap. 1987, 12, 419-426. DOI: https://doi.org/10.1111/j.1365-2710.1987.tb00556.x

- Vikas, S. Pradeep, K. Devender, P. Biological importance of the indole nucleus in recent years: a comprehensive review, J. Het. Chem. 2010, 47, 491.

- Prakash, B. Amuthavalli, A. Edison, D. Sivaramkumar, M. Velmurugan, R. Novel indole derivatives as potential anticancer agents: design, synthesis and biological screening. Med. Chem. Res. 2018, 27(1): 321-331. DOI: https://doi.org/10.1007/s00044-017-2065-9

- Singh, T. Singh, O. Recent progress in biological activities of indole and indole alkaloids. Mini Rev. Med. Chem. 2018, 18(1):9-25. DOI: https://doi.org/10.2174/1389557517666170807123201

- Kumari, S. Pramod, K. Nitin, K. Imidazole and its biological activities: A review. Der Chemica Sinica. 2010, 1(3): 36-47.

- Perumal, G. Ponnusamy, P. Kaliappillai, V. Magda, H. Mohd, S. Akbar, I. Radhakrishnan, S. Synthesis and Cytotoxic Activity of Novel Indole Derivatives and Their in-silico Screening on Spike Glycoprotein of SARS-CoV-2. Front. Mol. Biosci., 2021, 8, 1-11 DOI: https://doi.org/10.3389/fmolb.2021.637989

- Giovannali, P. Stella, C. Btissame, E. Daniela, C. Barbara, P. Girolamo, C. Godefridus, J. Patrizia, D. Elisa, G. Biological Evaluation of the Antiproliferative and Anti-migratory Activity of a Series of 3-(6-Phenylimidazo[2,1-b] [1,3,4] thiadiazol -2-yl)-1H-indole Deriva-tives Against Pancreatic Cancer Cells. Anticancer Res., 2019, 39(7): 3615-3620. DOI: https://doi.org/10.21873/anticanres.13509

- Mossaraf, H. Ashis K. A review on heterocyclic: synthesis and their application in medicinal chemistry of imidazole moiety. Sci. J. Chem. 2018, 6(5): 83-94. DOI: https://doi.org/10.11648/j.sjc.20180605.12

- Monther, F. Al-Smaism, R. Ammar I. Synthesis, Characterization of Some New 2-Azetidinone Derivatives. Al-Mustansiriyah Journal of Pharmaceutical Sciences (AJPS), 2015, 15 (2): 21-28. DOI: https://doi.org/10.32947/ajps.v15i2.167

- Entesar, O. Raad, M. Khalida, A. Synthesis, Characterization and Antibacterial Studies of 2-azetidinones Compounds Derived from Amoxicillin. Al-Mustansiriyah Journal of Pharmaceutical Sciences (AJPS), 2015, 15(1): 14-23. DOI: https://doi.org/10.32947/ajps.v15i1.160

- Brunton, L. Lazo, J. Parker, K. "Goodman and Gilmans: Pharmalogical Basis of Therapeutics" 11th ed. The McGraw-Hill Companirs, New York, 2006, 56.

- Furtado, G. Perdiz, L. Medeiros, E. The effect of a 4th generation cephalosporin upon the incidence of multidrug-resistant G (-) bacteria in a non-teaching hospital, Am. J. Infect. Dis. 2008, 4(4): 267-271. DOI: https://doi.org/10.3844/ajidsp.2008.267.271

- Rho, H. Baek, H. Kim, D. Chang, I. A convenient method for the preparation of Alkanolamides. Bull Korean Chem. Soc. 2006, 27(4): 584-586. DOI: https://doi.org/10.5012/bkcs.2006.27.4.584

- Prashad, M. Har, D. Hu, B. Hong, Y. Girgis, M. Chaudhary, A. Blacklock, T. Marterer, W. Process development of a large-scale synthesis of TKA731: A tachykinin receptor antagonist. Org. Process Res. Dev. 2004, 8(3): 330-340. DOI: https://doi.org/10.1021/op0341824

- Silverstein, R. Webster, X. Kiemle, D. "Spectrometric identification of organic compounds" 7th ed. Wiley-Interscience. New York. 2005.

- Daina, A. Michielin, O. Zoete, V. SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Scientific reports. 2017, 7(1): 1-13. DOI: https://doi.org/10.1038/srep42717

- Nawaz, F. Ozair, A. Ahmad, P. Moshahid, A. Mohd, J. Nadeem, S. Faheem, H. Mukund, J. 3′-(4-(Benzyloxy) phenyl)-1′-phenyl-5-(heteroaryl/aryl)-3, 4-dihydro-1′H, 2H- [3, 4-bipyrazole] 2- carboxamides as EGFR kinase inhibitors: Synthesis, anticancer evaluation, and molecular docking studies. Arch. Pharm. 2020, 353(4): 1900262. DOI: https://doi.org/10.1002/ardp.201900262

- Tao, C. Elizabeth, A. Christopher, R. Sivaprakash S. Marianne, P. Michael, N. Weirui,C. Detecting a quasi-stable imine species on the reaction pathway of SHV 1β lactamase and 6β-(hydroxymethyl)penicillanic acid sulfone. Biochem. Art. 2015, 54(3): 734-743. DOI: https://doi.org/10.1021/bi501197t

- Lipinski, A. Lombardo, F. Dominy, B. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Deliv. Rev., 2001, 46(1): 3-26. DOI: https://doi.org/10.1016/S0169-409X(00)00129-0

- Palm, K. Stenberg, P. Luthman, K. Artursson, P. Polar molecular surface properties predict the intestinal absorption of drugs in humans. Pharm. Res. 1997, 14(5): 568-571. DOI: https://doi.org/10.1023/A:1012188625088

- Verdonk, M. Cole, J. Hartshorn, M. Murray, C. Taylor, R. Improved protein–ligand docking using GOLD. Proteins: Structure,Function, and Bioinformatics. 2003, 52(4): 609-623. DOI: https://doi.org/10.1002/prot.10465

- Adeniyi, A. Ajibade, P. Comparing the suitability of autodock, gold and glide for the docking and predicting the possible targets of Ru (II)-based complexes as anticancer agents. Molecules. 2013,18(4): 3760-3778. DOI: https://doi.org/10.3390/molecules18043760

- Cho, S. Kim, S. Jin, Z. Yang, H. Han, D. Baek, N. Jo, J. Cho, C. Park, J. Shimizu, M. Jin, Y. Isoliquiritigenin, a chalcone compound a positive allosteric modulator of GABA receptors and shows hypnotic effects. Biochem. & Biophys. Res. Commun. 2014, 413(4): 637-644. DOI: https://doi.org/10.1016/j.bbrc.2011.09.026

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Published

2022-04-19

How to Cite

Yasir F. Muhsin, Shakir M. Alwan, & Ayad Kareem Khan. (2022). Design, Molecular Docking, Synthesis of Aromatic Amino Acids Linked to Cephalexin. Al Mustansiriyah Journal of Pharmaceutical Sciences, 21(3), 25–34. https://doi.org/10.32947/ajps.v21i3.794