Synthesis and Characterization of New 5-Fluoroisatin-Chalcone Conjugates with Expected Antimicrobial Activity
DOI:
https://doi.org/10.31351/vol33iss2pp138-146Keywords:
4-aminoacetophenone, 5-fluoroisatin, antimicrobial activity, aromatic aldehydes, chalcone, Schiff bases.Abstract
Pathogenic microorganisms are becoming more and more resistant to antimicrobial agents. So the synthesis of new antimicrobial agents is very important. In this work, new 5-fluoroisatin-chalcone conjugates 5(a–g) were synthesized based on previous research that showed the modifications of the isatin moiety led to the synthesis of many derivatives that have antimicrobial activity. 4-aminoacetophenone reacts with 5-fluoroisatin to form Schiff base (3), which in turn reacts with two different groups of aromatic (carbocyclic and heterocyclic) aldehydes 4(a–g) separately to form the final compounds 5(a–g). Proton-nuclear magnetic resonance (¹H-NMR) and Fourier-transform infrared (FT-IR) spectroscopy were used to confirm the chemical structures of the newly prepared compounds. Finally, the final compounds, 5-fluoroisatin-chalcone conjugates 5(a–g), were screened for their antimicrobial activities and compared with three different references: vancomycin, ciprofloxacin, and fluconazole. They appeared to be good candidates as antibacterial agents against E. coli and S. aureus as well as antifungal agents against C. albicans. In general and for comparison, the antifungal activity of the final compounds 5(a–g) was more potent than their antibacterial activity. Finally, for the antimicrobial activity, the most active compound of these series was compound 5e, while compound 5g was the least active one.
Received16/4 /2023
Accepted 26/6/2023
Published 27/6/2024
References
Jarrahpour A, Sheikh J, Mounsi I El, Juneja H, Hadda T Ben. Computational evaluation and experimental in vitro antibacterial, antifungal and antiviral activity of bis-Schiff bases of isatin and its derivatives. Med Chem Res. 2013;22(3):1203–11.
Mantravadi PK, Kalesh KA, Dobson RCJ, Hudson AO, Parthasarathy A. The quest for novel antimicrobial compounds: Emerging trends in research, development, and technologies. antibiotics. 2019;8(8).
Moellering RC. Discovering new antimicrobial agents. Int J Antimicrob Agents. 2011;37(1):2–9.
Schulz LT, Kim SY, Hartsell A, Rose WE. Antimicrobial stewardship during a time of rapid antimicrobial development: Potential impact on industry for future investment. Diagn Microbiol Infect Dis. 2019;95(3).
Sumrra SH, Atif AH, Zafar MN, Khalid M, Tahir MN, Nazar MF, et al. Synthesis, crystal structure, spectral and DFT studies of potent isatin derived metal complexes. J Mol Struct. 2018;1166:110–20.
Varun, Sonam, Kakkar R. Isatin and its derivatives: a survey of recent syntheses, reactions, and applications. Medchemcomm. 2019;10(3):351–68.
Deswal S, Naveen, Tittal RK, Ghule Vikas D, Lal K, Kumar A. 5-Fluoro-1H-indole-2,3-dione-triazoles- synthesis, biological activity, molecular docking, and DFT study. J Mol Struct. 2020;1209.
Singh G, Kalra P, Singh A, Sharma G, Sanchita, Pawan, et al. A quick microwave preparation of isatin hydrazone schiff base conjugated organosilicon compounds: Exploration of their antibacterial, antifungal, and antioxidative potentials. J Organomet Chem. 2021;953.
Yousef MA, Ali AM, El-Sayed WM, Quayed WS, Farag HHA, Aboul-Fadl T. Design and synthesis of novel isatin-based derivatives targeting cell cycle checkpoint pathways as potential anticancer agents. Bioorg Chem. 2020;105.
Li W, Zhao SJ, Gao F, Lv ZS, Tu JY, Xu Z. Synthesis and In Vitro Anti-Tumor, Anti-Mycobacterial and Anti-HIV Activities of Diethylene-Glycol-Tethered Bis-Isatin Derivatives. ChemistrySelect. 2018; 3(36) :10250 –4.
Deng JL, Liu XC, Cai GW, Zhang G, Hu L, Qiu L, et al. Heteronuclear 5-Fluoroisatin Dimers: Design, Synthesis, and Evaluation of Their In Vitro Anti-mycobacterial Activities. J Heterocycl Chem. 2018;55(6):1509–13.
Çavuş MS, Yakan H, Muğlu H, Bakır T. Novel carbohydrazones including 5-substituted isatin: Synthesis, characterization, and quantum-chemical studies on the relationship between electronic and antioxidant properties. J Phys Chem Solids. 2020;140.
Emami S, Valipour M, Kazemi Komishani F, Sadati-Ashrafi F, Rasoulian M, Ghasemian M, et al. Synthesis, in silico, in vitro and in vivo evaluations of isatin aroylhydrazones as highly potent anticonvulsant agents. Bioorg Chem. 2021;112.
Obafemi CA, Adegbite OB, Fadare OA, Iwalewa EO, Omisore NO, Sanusi K, et al. Tryptanthrin from microwave-assisted reduction of isatin using solid-state-supported sodium borohydride: DFT calculations, molecular docking and evaluation of its analgesic and anti-inflammatory activity. heliyon. 2021;7(1).
Manan MAFA, Crouse KA, Tahir MIM, Rosli R, How FNF, Watkin DJ, et al. Synthesis, characterization and cytotoxic activity of S- benzyldithiocarbazate Schiff bases derived from 5-fluoroisatin, 5-chloroisatin, 5-bromoisatin and their crystal structures. J Chem Crystallogr. 2011;41(11):1630–41.
Abbas SY, Farag AA, Ammar YA, Atrees AA, Mohamed AF, El-Henawy AA. Synthesis, characterization, and antiviral activity of novel fluorinated isatin derivatives. Monatshefte fur Chemie. 2013;144(11):1725–33.
Goodman VL, Rock EP, Dagher R, Ramchandani RP, Abraham S, Gobburu JVS, et al. Approval summary: Sunitinib for the treatment of imatinib refractory or intolerant gastrointestinal stromal tumors and advanced renal cell carcinoma. Clin Cancer Res. 2007;13(5):1367–73.
Heaton CM, Fernandes AFA, Jark PC, Pan X. Evaluation of toceranib for treatment of apocrine gland anal sac adenocarcinoma in dogs. J Vet Intern Med. 2020;34(2):873–81.
Eldehna WM, Al-Wabli RI, Almutairi MS, Keeton AB, Piazza GA, Abdel-Aziz HA, et al. Synthesis and biological evaluation of certain hydrazonoindolin-2-one derivatives as new potent anti-proliferative agents. J Enzyme Inhib Med Chem. 2018;33(1):867–78.
Kaduk JA, Gates-Rector S, Blanton TN. Crystal structure of toceranib, C22H25FN4O2. Cambridge Univ Press behalf Int Cent Diffr Data. 2023;1–6.
Ramadan MAG, Baloglu MC, Altunoglu YC, Kandemirli F, Burhan H, Aygün A, et al. Evaluation of Biological Activity of 5-Fluoro-Isatin Thiosemicarbazone Derivatives. J Nanostruct. 2020;10(3):509–17.
Kamoon RA, Jawad Al-Mudhafar MM, Omar TNA. Synthesis, characterization and antimicrobial evaluation of new Azo compounds derived from sulfonamides and Isatin Schiff base. Int J Drug Deliv Technol. 2020;10(1):150–5.
Salehi B, Quispe C, Chamkhi I, El Omari N, Balahbib A, Sharifi-Rad J, et al. Pharmacological Properties of Chalcones: A Review of Preclinical Including Molecular Mechanisms and Clinical Evidence. Front Pharmacol. 2021;11.
Rajendran G, Bhanu D, Aruchamy B, Ramani P, Pandurangan N, Bobba KN, et al. Chalcone: A Promising Bioactive Scaffold in Medicinal Chemistry. Pharmaceuticals. 2022;15(10):1250.
Zhuang C, Zhang W, Sheng C, Zhang W, Xing C, Miao Z. Chalcone: A Privileged Structure in Medicinal Chemistry. Chem Rev. 2017;117(12):7762–810.
Lihumis HS, Aowda SA. Synthesis and identification of some Imino Chalcone derivatives with evaluating their anti-oxidant activity. Iraqi J Sci. 2021;(Special Issue 2):1–16.
Tekale S, Mashele S, Pooe O, Thore S, Kendrekar P, Pawar R. Biological Role of Chalcones in Medicinal Chemistry. In: Vector-Borne Diseases - Recent Developments in Epidemiology and Control. 2020.
Tukur AR, Habila JD, Ayo RG-O, Lyun ORA. Synthesis, Reactions and Pharmacological Applications of Chalcones and Their Derivatives- A Mini Review. J Chem Rev. 2022;4(2):100–19.
Ezekwem JE, Visagaperumal D, Chandy V. Synthesis, Characterization and Anti-Bacterial Activity of Isatin Schiff Base Derivatives. Vol. 3, Asian Journal of Chemistry and Pharmaceutical Sciences. 2018. p. 7–12.
Gupta AK, Bharadwaj M, Mehrotra R. Eco-friendly Polyethylene Glycol-400 as a Rapid and Efficient Recyclable Reaction Medium for the Synthesis of Anticancer Isatin-linked Chalcones and Their 3-Hydroxy Precursor. J Heterocycl Chem. 2019;56(2):703–9.
Singh A, Fong G, Liu J, Wu Y-H, Chang K, Park W, et al. Synthesis and Preliminary Antimicrobial Analysis of Isatin−Ferrocene and Isatin−Ferrocenyl Chalcone Conjugates. ACS Omega. 2018;3(5):5808−5813.
Mishra R, Chaurasia H, Singh VK, Naaz F, Singh RK. Molecular modeling, QSAR analysis and antimicrobial properties of Schiff base derivatives of isatin. J Mol Struct. 2021;1243:130763.
Shakir TH, Al-Mudhafar MMJ. Synthesis and preliminary antimicrobial evaluation of schiff bases of N-Benzyl isatin derivatives. Syst Rev Pharm. 2020;11(12):1950–5.
Hassan OM, Sarsam SW. Synthesis, characterization and preliminary anti-inflammatory evaluation of new fenoprofen hydrazone derivatives. Iraqi J Pharm Sci. 2021;29(2):239–44.
Syam S, Abdelwahab SI, Al-Mamary MA, Mohan S. Synthesis of chalcones with anticancer activities. Molecules. 2012;17(6):6179–95.
Akinpelu DA, Abioye EO, Aiyegoro OA, Akinpelu OF, Okoh AI. Evaluation of antibacterial and antifungal properties of alchornea laxiflora (Benth.) Pax. & Hoffman. Evidence-based Complement Altern Med. 2015;2015.
Sani U, Na’ibi HU, Dailami SA. In vitro antimicrobial and antioxidant studies on N-(2- hydroxylbenzylidene) pyridine -2-amine and its M(II) complexes. Niger J Basic Appl Sci. 2017;25(1):81–8.
Sadia Afrin Dalia, Farhana Afsan, Md. Saddam Hossain MN, Khan, CM Zakaria MK-E-Z and MMA. A short review on chemistry of schiff base metal complexes and their catalytic application Evaluation of groundwater quality View project schiff base View project A short review on chemistry of schiff base metal complexes and their catalytic application. Int J Chem Stud. 2018;6(3):2859–66.
Enchev V, Mehandzhiyski AY. Computational insight on the chalcone formation mechanism by the Claisen–Schmidt reaction. Int J Quantum Chem. 2017;117(11):1–8.
Menozzi G, Merello L, Fossa P, Schenone S, Ranise A, Mosti L, et al. Synthesis, antimicrobial activity and molecular modeling studies of halogenated 4-[1H-imidazol-1-yl(phenyl)methyl]-1,5-diphenyl-1H-pyrazoles. Bioorganic Med Chem. 2004;12(20):5465–83.
Xu Z, Zhao S-J, Lv Z-S, Gao F, Wang Y, Zhang F, et al. Fluoroquinolone-isatin hybrids and their biological activities. Eur J Med Chem. 2019;162:396–406.
Downloads
Published
Issue
Section
License
Copyright (c) 2024 Iraqi Journal of Pharmaceutical Sciences( P-ISSN 1683 - 3597 E-ISSN 2521 - 3512)
![Creative Commons License](http://i.creativecommons.org/l/by/4.0/88x31.png)
This work is licensed under a Creative Commons Attribution 4.0 International License.