Molecular Docking, ADME Study, Synthesis, Characterization and Preliminary Antimicrobial Activity Evaluation of New Phenylalanine Derivatives of Sulfonamide
DOI:
https://doi.org/10.22317/jcms.v10i6.1673Keywords:
Antimicrobial, Molecular docking, Schiff base, Sulfonamide, Zone Inhibition (ZI).Abstract
Objective: The main objective for this study is the synthesis of a series of new phenylalanine derivatives of sulfonamide.
Methods: The final compounds P1-P4 were synthesized starting with the synthesis of two intermediate compounds Ⅰ and Ⅱ, which were reacted with each other in to get compound Ⅲ. Then, the later was reacted with hydrazine hydrate led to the compound Ⅳ that was eventually reacted with different aldehydes to produce the target compounds. Characterization of their structure was performed using ATR-FTIR and HNMR spectroscopies. The assessment of the antimicrobial activity was done for all of them. The final compounds were subjected to molecular docking and ADME study, which were conducted in comparison to standard drugs (sulfamethoxazole and sulfadiazine).
Results: The synthesized final compounds exerted a broad inhibitory activity on certain microbes, including Gram-positive bacteria (Staphylococcus aureus and Streptococcus pneumonia), Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa), and one fungus (Candida albicans). However, compounds P3 and P4 had the highest activity. The molecular docking findings represented compounds P1, P2 and P3 with high docking scores compared with standard drugs, while the ADME study showed a desired drug-likeness and accepted pharmacokinetic properties.
Conclusions: The target compounds were successfully synthesized with good antimicrobial activity. The compounds P1, P2 and P3 recorded the highest docking scores, while all the final compounds had good ADME findings.
References
Hassan OM, Sarsam SW. Synthesis, characterization and preliminary anti-inflammatory evaluation of new etodolac derivatives. Iraqi Journal of Pharmaceutical Sciences (P-ISSN 1683-3597 E-ISSN 2521-3512). 2019 Jun 9;28(1):106-12. https://doi.org/10.31351/vol28iss1pp107-113.
Azzam RA, Elsayed RE, Elgemeie GH. Design, synthesis, and antimicrobial evaluation of a new series of N-sulfonamide 2-pyridones as dual inhibitors of DHPS and DHFR enzymes. ACS omega. 2020 Apr 28;5(18):10401-14. https://doi.org/10.1021/acsomega.0c00280
Mondal S, Malakar S. Synthesis of sulfonamide and their synthetic and therapeutic applications: Recent advances. Tetrahedron. 2020 Nov 27;76(48):131662. https://doi.org/10.1016/j.tet.2020.131662
Carta F, Scozzafava A, Supuran CT. Sulfonamides: a patent review (2008–2012). Expert opinion on therapeutic patents. 2012 Jul 1;22(7):747-58.
https://doi.org/10.1517/13543776.2012.698264.
Wainwright M, Kristiansen JE. On the 75th anniversary of Prontosil. Dyes and Pigments. 2011 Mar 1;88(3):231-4. https://doi.org/10.1016/j.dyepig.2010.08.012.
Norman Hodges. Antibiotics and synthetic antimicrobial agent. in: Gilmore BF, Denyer SP, editors. Hugo and Russell's pharmaceutical microbiology. John Wiley & Sons; 2011.p 183-184.
Nunes OC, Manaia CM, Kolvenbach BA, Corvini PF. Living with sulfonamides: a diverse range of mechanisms observed in bacteria. Applied microbiology and biotechnology. 2020 Dec;104(24):10389-408. https://doi.org/10.1007/s00253-020-10982-5
Tenover FC. Mechanisms of antimicrobial resistance in bacteria. The American journalofmedicine.2006Jun1;119(6):S3-10. https://doi.org/10.1016/j.amjmed.2006.03.011.
Levy SB, Marshall B. Antibacterial resistance worldwide: causes, challenges and responses. Nature medicine. 2004 Dec;10(Suppl 12): S122-9. https://doi.org/10.1038/nm1145
John M. Beale, JR. Anti-infective Agents .in: Beale JM, Block J, Hill R. Organic medicinal and pharmaceutical chemistry. Philadelphia: Lippincott Williams & Wilkins; 2010.p228-229.
Wulf NR, Matuszewski KA. Sulfonamide cross-reactivity: is there evidence to support broad cross-allergenicity? American journal of health-system pharmacy. 2013 Sep 1;70(17):1483-94. https://doi.org/10.2146/ajhp120291.
Sadler BM, Stein DS. Clinical pharmacology and pharmacokinetics of amprenavir. Annals of Pharmacotherapy. 2002 Jan;36(1):102-18. https://doi.org/10.1345/aph.10423.
Wire MB, Shelton MJ, Studenberg S. Fosamprenavir: clinical pharmacokinetics and drug interactions of the amprenavir prodrug. Clinical pharmacokinetics. 2006 Feb; 45:137-68. https://doi.org/10.2165/00003088-200645020-00002.
Choquet-Kastylevsky G, Vial T, Descotes J. Allergic adverse reactions to sulfonamides. Current Allergy and Asthma Reports. 2002 Jan;2(1):16-25. https://doi.org/10.1007/s11882-002-0033-y.
Dorn JM, Alpern M, McNulty C, Volcheck GW. Sulfonamide drug allergy. Current Allergy and Asthma Reports. 2018 Jul; 18:1-0. https://doi.org/10.1007/s11882-018-0791-9.
Ali RM, Al-Hamashi AA. Molecular docking, ADMET, molecular dynamic simulation, synthesis, and preliminary antiproliferative study of 1, 2, 4-thiadiazole derivatives as possible histone deacetylase inhibitors. Tropical Journal of Pharmaceutical Research. 2024 Sep 6;23(7):1069-76. https://doi.org/10.4314/tjpr.v23i7.4.
Mosleh AA, Dakhel ZA. Molecular docking, microwave-assisted synthesis, characterization, and preliminary evaluation of the anti-microbial activity of new sulfonamide derivatives of the 1, 2, 4-triazole-3-thiol ring system. Pharmacia. 2024 Sep 3; 71:1-9. https://doi.org/10.3897/pharmacia.71.e132720
Saeed AM, Al-Hamashi AA. Molecular Docking, ADMET Study, Synthesis, Characterization and Preliminary Antiproliferative Activity of Potential Histone Deacetylase Inhibitors with Isoxazole as New Zinc Binding Group. Iraqi Journal of Pharmaceutical Sciences (P-ISSN 1683-3597 E-ISSN 2521-3512). 2023 Nov 3;32(Suppl.):188-203. https://doi.org/10.31351/vol32issSuppl.pp188-203
Ovung A, Bhattacharyya J. Sulfonamide drugs: Structure, antibacterial property, toxicity, and biophysical interactions. Biophysical reviews. 2021 Apr;13(2):259-72. https://doi.org/10.1007/s12551-021-00795-9
Gavernet L, Elvira JE, Samaja GA, Pastore V, Sella Cravero M, Enrique A, et al, Synthesis and anticonvulsant activity of amino acid-derived sulfamides. Journal of medicinal chemistry. 2009 Mar 26;52(6):1592-601. https://doi.org/10.1021/jm800764p.
Kamms ZD, Hadi MK. Synthesis, Characterization and preliminary Anti-Microbial Evaluation of New Ibuprofen Hydrazide Derivatives. Pakistan Journal of Medical & Health Sciences. 2022 Apr 27;16(03):693-.
Abdulrahman HS, Hassan Mohammed M, Al-Ani LA, Ahmad MH, Hashim NM, Yehye WA. Synthesis of phthalimide imine derivatives as a potential anticancer agent. Journal of Chemistry. 2020;2020(1):3928204. https://doi.org/10.1155/2020/3928204.
Kanaan S, Omar TN. Synthesis and Preliminary Anti-Inflammatory and Anti-Microbial Evaluation of New 4, 5-Dihydro-1H-Pyrazole Derivatives. Iraqi Journal of Pharmaceutical Sciences (P-ISSN 1683-3597 E-ISSN 2521-3512). 2023 Nov 4;32(Suppl.):262-70. https://doi.org/10.31351/vol32issSuppl.pp262-270.
Franconi I, Lupetti A. In Vitro Susceptibility Tests in the Context of Antifungal Resistance: Beyond Minimum Inhibitory Concentration in Candida spp. Journal of Fungi. 2023 Dec 12;9(12):1188. https://doi.org/10.3390/jof9121188.
Abduljabbar TT, Hadi MK. Synthesis, characterization and antibacterial evaluation of some coumarin derivatives. Iraqi Journal of Pharmaceutical Sciences (P-ISSN 1683-3597 E-ISSN 2521-3512). 2021 Jun 19;30(1):249-57. https://doi.org/10.31351/vol30iss1pp249-257.
Mahdi L, Al Mathkhury HJ, Sana’a AK, Rasool KH, Zwain L, Salman IM, et al, Antibacterial activity of lactobacillus buchneri bacteriocin against vibrio parahaemolyticus. current applied science and technology. 2017;17(1):81-6. https://li01.tci-thaijo.org/index.php/cast/article/view/129081.
Tang C, Ye Y, Feng Y, Quinn RJ. TCM, brain function and drug space. Nat Prod Rep. 2015;33(1):6–25. https://doi.org/10.1039/C5NP00049A
Ntie-Kang F. An in-silico evaluation of the ADMET profile of the StreptomeDB database. SpringerPlus. 2013;2(1):353. https://doi.org/10.1186/2193-1801-2-353.
EL KOLLI ME. Mechanism of antimicrobial activity and antioxidant activities of the essential oil and the methanolic extract of carum montanum from Algeria. Annals of Agricultural Science, Moshtohor. 2018 Apr 1;56(4th ICBAA):253-62. https://dx.doi.org/10.21608/assjm.2018.18553.
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