Synthesis, Characterization of Schiff's and Mannich bases of 5-Fluoroisatin and Preliminary Antimicrobial Evaluation
Main Article Content
Keywords
5-Fluoroisatin, Secondary amines, Mannich bases, Schiff bases, Antimicrobial activity.
Abstract
With the aim of developing potential antimicrobials, a series of new 5-fluoroisatin derivatives incorporated with different secondary amines (piperidine, morpholine, pyrrolidine, dimethylamine, and diphenylamine) for monomer, and (piperazine) in case of dimer Mannich bases, separately in presence of formaldehyde to obtain Mannich bases of 5-fluoroisatin derivatives, which then each Mannich derivatives reacts with phenylhydrazine to form Schiff bases as final products. The resulting compounds were characterized by two spectroscopic analyses; (Fourier- transform infrared) FT-IR and proton nuclear magnetic resonance spectroscopy (¹H-NMR). In addition, the in vitro antibacterial and antifungal activities were tested against some human pathogenic microorganisms by employing the well-diffusion technique. The majority of these derivatives showed activity against several microorganisms. The relationship between the functional group variation and the biological activity of the evaluated compounds is discussed. From the comparison, the resulting compounds, (4b and 4d) were determined to be the most potent compounds. Dimer 6 exhibits an acceptable activity toward the bacterial stain; P. mirabilis.
References
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25. Zhang YZ, Du HZ, Liu HL, He QS, Xu Z. Isatin dimers, and their biological activities. Archiv der Pharmazie. 2020 Mar;353(3):1900299.
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27. Balouiri M, Sadiki M, Ibnsouda SK. Methods for in vitro evaluating antimicrobial activity: A review. Journal of pharmaceutical analysis. 2016 Apr 1;6(2):71-9.
28. Al-Kadhimi AA, Al-Azzawi NK, Khalaf AI. Facile synthesis of Schiff and Mannich bases of isatin derivatives. Journal of Chemical, Biological and Physical Sciences. 2015;5(3):2338-49.
29. Karalı N, Gürsoy A, Kandemirli F, Shvets N, Kaynak FB, Özbey S, Kovalishyn V, Dimoglo A. Synthesis and structure–antituberculosis activity relationship of 1H-indole-2, 3-dione derivatives. Bioorganic & medicinal chemistry. 2007 Sep 1;15(17):5888-904.
2. Pal M, Sharma NK, Priyanka, Jha KK, Synthetic and biological multiplicity of isatin: A Review, Journal of Advanced Scientific Research, 2011; 2(2): 35-44.
3. Kakkar R. Isatin and its derivatives: a survey of recent syntheses, reactions, and applications. MedChemComm. 2019;10(3):351-68.
4. Jarrahpour AA, Khalili D. Synthesis of 3, 3-[methylenebis (3, 1-phenylenenitrilo)] bis [1, 3-dihydro]-2H-indol-2-one as a novel bis-Schiff base. Molbank. 2005 Oct 1;2005(4):M437.
5. Jarrahpour A, Khalili D, De Clercq E, Salmi C, Brunel JM. Synthesis, antibacterial, antifungaland antiviral activity evaluation of some new bis-Schiff bases of isatin and their derivatives. Molecules. 2007 Aug 7;12(8):1720-30.
6. Varma RS, Nobles WL. Synthesis and antiviral and antibacterial activity of certain N-dialkylaminomethylisatin β-thiosemicarbazones. Journal of Medicinal Chemistry. 1967 Sep;10(5):972-4.
7. Jarrahpour AA, Khalili D. Synthesis of 3, 3-[methylenebis (3, 1-phenylenenitrilo)] bis [1, 3-dihydro]-2H-indol-2-one as a novel bis-Schiff base. Molbank. 2005 Oct 1;2005(4):M437.
8. Shakir TH, Al-Mudhafar MM. Synthesis and Preliminary Antimicrobial Evaluation Of Schiff Bases of N-Benzyl Isatin Derivatives. Systematic Reviews in Pharmacy. 2020 Dec 1;11(12):1950-5.
9. Chinnasamy RP, Sundararajan R, Govindaraj S. Synthesis, characterization, and analgesic activity of novel Schiff base of isatin derivatives. Journal of advanced pharmaceutical technology & research. 2010 Jul;1(3):342.
10. Varma RS, Khan IA. Potential biologically active agents. X. Synthesis of 3-arylimino-2-indolinones, and their 1-methyl-and 1-morpholino/piperidinomethyl derivatives as excystment and cysticidal agents against Schizopyrenus russelli. Polish Journal of Pharmacology and Pharmacy. 1977 Sep 1;29(5):549-54.
11. Sarciron ME, Audin P, Delabre I, Gabrion C, Petavy AF, Paris J. Synthesis of propargylic alcohols and biological effects on Echinococcus multilocularis metacestodes. Journal of pharmaceutical sciences. 1993 Jun;82(6):605-9.
12. El-Sawi EA, Mostafa TB, Mostafa BB. Studies on the molluscicidal action of some isatin derivatives against Biomphalaria alexandrina in Egypt. Journal of the Egyptian Society of Parasitology. 1998 Aug 1;28(2):481-6.
13. Manan MA, Crouse KA, Tahir MI, Rosli R, How FN, Watkin DJ, Slawin AM. Synthesis, characterization and cytotoxic activity of S-benzyldithiocarbazate Schiff bases derived from 5-fluoroisatin, 5-chloroisatin, 5-bromoisatin and their crystal structures. Journal of Chemical Crystallography. 2011 Nov;41:1630-41.
14. Smart BE. Fluorine substituent effects (on bioactivity). Journal of Fluorine Chemistry. 2001 Jun 1;109(1):3-11.
15. Isanbor C, O’Hagan D. Fluorine in medicinal chemistry: A review of anti-cancer agents. Journal of Fluorine Chemistry. 2006 Mar 1;127(3):303-19.
16. Podichetty AK, Faust A, Kopka K, Wagner S, Schober O, Schäfers M, Haufe G. Fluorinated isatin derivatives. Part 1: synthesis of new N-substituted (S)-5-[1-(2-methoxymethylpyrrolidinyl) sulfonyl] isatins as potent caspase-3 and-7 inhibitors. Bioorganic & medicinal chemistry. 2009 Apr 1;17(7):2680-8.
17. Prenen H, Cools J, Mentens N, Folens C, Sciot R, Schöffski P, Van Oosterom A, Marynen P, Debiec-Rychter M. Efficacy of the kinase inhibitor SU11248 against gastrointestinal stromal tumor mutants refractory to imatinib mesylate. Clinical Cancer Research. 2006 Apr 15;12(8):2622-7. 18. Motzer RJ, Michaelson MD, Redman BG, Hudes GR, Wilding G, Figlin RA, Ginsberg MS, Kim ST, Baum CM, DePrimo SE, Li JZ. Activity of SU11248, a multitargeted inhibitor of vascular endothelial growth factor receptor and platelet-derived growth factor receptor, in patients with metastatic renal cell carcinoma. Journal of Clinical Oncology. 2006 Jan 1;24(1):16-24.
19. Silver FP, Popp FD, Casey AC, Chakraborty DP, Cullen E, Kirsch WR, McCleskey JE, Sinha B. Synthesis of Potential Antineoplastic Agents. XIX. Some 5-(ω-Chloroacylamino) quinolines and 4-and 5-(ω-Chloroacylamino) isoquinolines. Journal of Medicinal Chemistry. 1967 Sep;10(5):986-7. 20. Al-Mudhafar MM, Omar TN, Abdulhadi SL. Bis-Schiff Bases of Isatin Derivatives Synthesis, and their Biological Activities: A Review. Al Mustansiriyah Journal of Pharmaceutical Sciences. 2022 Jul 4;22(1):23-48.
21. Ganim Ramadan MA, Baloglu MC, Celik Altunoglu Y, Kandemirli F, Burhan H, Aygün A, Sayiner H, Ozyigit F, Sen F. Evaluation of Biological Activity of 5-Fluoro-Isatin Thiosemicarbazone Derivatives. Journal of Nanostructures. 2020 Jul 1;10(3):509-17.
22. Abbas SY, Farag AA, Ammar YA, Atrees AA, Mohamed AF, El-Henawy AA. Synthesis, characterization, and antiviral activity of novel fluorinated isatin derivatives. Monatshefte für Chemie-Chemical Monthly. 2013 Nov;144:1725-33.
23. Al-Mudhafar MM, Kamoon RA. Synthesis, characterization, and antimicrobial activity of new Schiff’s and Mannich bases of isatin and isatin derivatives. J. Glob. Pharma Technol. 2020;12(1):529-36.
24. Patel A, Bari S, Talele G, Patel J, Sarangapani M. Synthesis and antimicrobial activity of some new isatin derivatives. Iranian Journal of Pharmaceutical Research,4, 2006, 249-254.
25. Zhang YZ, Du HZ, Liu HL, He QS, Xu Z. Isatin dimers, and their biological activities. Archiv der Pharmazie. 2020 Mar;353(3):1900299.
26. Fröhlich T, Çapcı Karagöz A, Reiter C, Tsogoeva SB. Artemisinin-derived dimers: potent antimalarial and anticancer agents. Journal ofmedicinal chemistry. 2016 Aug 25;59(16):7360-88.
27. Balouiri M, Sadiki M, Ibnsouda SK. Methods for in vitro evaluating antimicrobial activity: A review. Journal of pharmaceutical analysis. 2016 Apr 1;6(2):71-9.
28. Al-Kadhimi AA, Al-Azzawi NK, Khalaf AI. Facile synthesis of Schiff and Mannich bases of isatin derivatives. Journal of Chemical, Biological and Physical Sciences. 2015;5(3):2338-49.
29. Karalı N, Gürsoy A, Kandemirli F, Shvets N, Kaynak FB, Özbey S, Kovalishyn V, Dimoglo A. Synthesis and structure–antituberculosis activity relationship of 1H-indole-2, 3-dione derivatives. Bioorganic & medicinal chemistry. 2007 Sep 1;15(17):5888-904.
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Published
Jun 4, 2023
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How to Cite
Mustafa Mahmood Mukhlif, & May Mohammed Jawad Al-Mudhafar. (2023). Synthesis, Characterization of Schiff’s and Mannich bases of 5-Fluoroisatin and Preliminary Antimicrobial Evaluation. Journal of Population Therapeutics and Clinical Pharmacology, 30(13), 381–389. https://doi.org/10.47750/jptcp.2023.30.13.039
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