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In vitro antioxidant activities and in silico molecular docking studies of N-substituted oxime derivatives

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Abstract

New N-substituted oxime derivatives (5b, 5d-g, 5i-k, and 5m) and known compounds (5a, 5c, 5h, 5g, 5l, and 5n-q) were obtained by reacting phenyl and butyl oxime chloride analogs with aniline, piperazine derivatives, piperidine, and diethylamine. Structures of all new compounds were determined by 1H NMR, 13C NMR, HRMS, and FTIR methods. All compounds were evaluated in vitro for their antiradical activity and hydrogen peroxide scavenging activity. Compounds 5g, 5h, 5i, 5j, 5k, 5l, 5m, and 5p have shown good antiradical activities with EC50 values < 1 (conc. antiradical (µM)/conc. DPPH (µM)). Similar results were obtained in the peroxide scavenging activity tests. These results have shown that piperidine and butyl substitution greatly increases the antiradical activity of the oximes. Compounds 5l and 5m were found to be the best radical scavengers. In addition, molecular docking studies were performed for compounds (5a-q) against CP450 (CYP1A2), NADPH oxidase, and Xanthine oxidase to predict their antioxidant capabilities through ROS-producing enzyme inhibitions.

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All experimental data were included in the manuscript. All spectral data can be found in Supplementary Material.

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References

  1. Ray PD, Huang BW, Tsuji Y (2012) Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling. Cell Signal 24:981–990

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Snezhkina AV, Kudryavtseva AV, Kardymon OL, Savvateeva MV, Melnikova NV et al (2019) ROS generation and antioxidant defense systems in normal and malignant cells. Oxid Med Cell Longev 1–17

  3. Pizzino G, Irrera N, Cucinotta M, Pallio G, Mannino F et al (2013) Oxidative stress: harms and benefits for human health. Oxid Med Cell Longev 1–13

  4. Costa JDS, Ramos RDS, Costa KDSL, Brasil DDSB, Silva CHTD (2018) An in silico study of the antioxidant ability for two caffeine analogs using molecular docking and quantum chemical methods. Molecules 23(11):2801

    Article  PubMed  PubMed Central  Google Scholar 

  5. Liu XH, Cui P, Song BA, Bhadury PS, Zhu HL et al (2008) Synthesis, structure and antibacterial activity of novel 1-(5-substituted-3-substituted-4,5-dihydropyrazol-1-yl)ethanone oxime ester derivatives. Bioorganic Med Chem 16:4075–4082

    Article  CAS  Google Scholar 

  6. Zhao H, Zhou M, Duan L, Wang W, Zhang J, Liang X et al (2013) Efficient synthesis and anti-fungal activity of oleanolic acid oxime esters. Molecules 18:3615–3629

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Kala TS, Latha DS, Sowjanya G, Swathi P, Bharathi V et al (2016) Synthesis, characterization and pharmacological evaluation of substituted N-benzyl isatin 3-oximes. J Glob Trends Pharm Sci 7:3057–3064

    CAS  Google Scholar 

  8. Harini ST, Kumar HV, Peethambar SK, Peethambar SK, Rangaswamy J et al (2013) Novel 2,6-bis(4-methoxyphenyl)-1-methylpiperidin-4-one oxime esters: synthesis and a new insight into their antioxidant and antimicrobial potential. Med Chem Res 23:1887–1898

    Article  Google Scholar 

  9. Özen T, Taş M (2009) Screening and evaluation of antioxidant activity of some amido-carbonyl oxime derivatives and their radical scavenging activities. J Enzyme Inhib Med Chem 24(5):1141–1147

    Article  PubMed  Google Scholar 

  10. Bolotin DS, Demakova MY, Legin AA, Suslonov VV, Nazarov AA et al (2017) Amidoxime platinum(II) complexes: pH-dependent highly selective generation and cytotoxic activity. New J Chem 41:6840–6848

    Article  CAS  Google Scholar 

  11. Worek F, Thiermann H, Wille T (2016) Oximes in organophosphate poisoning: 60 years of hope and despair. Chem Biol Interact 259:93–98

    Article  CAS  PubMed  Google Scholar 

  12. Markandewar RA, Baseer MA (2016) Exploring pharmacological signifıcance of piperazine scaffold. World J Pharm Res 5(7):1409–1420

    CAS  Google Scholar 

  13. Salat K, Moniczewski A, Salat R, Janaszek M, Filipek B et al (2012) Analgesic, anticonvulsant and antioxidant activities of 3-[4-(3-trifluoromethyl-phenyl)-piperazin-1-yl]-dihydrofuran-2-one dihydrochloride in mice. Pharmacol Biochem Behav 101:138–147

    Article  CAS  PubMed  Google Scholar 

  14. Prashanth MK, Revanasiddappa HD, Lokanatha Rai KM, Veeresh B (2012) Synthesis, characterization, antidepressant and antioxidant activity of novel piperamides bearing piperidine and piperazine analogues. Bioorganic Med Chem Lett 22:7065–7070

    Article  CAS  Google Scholar 

  15. Paulrasu K, Duraikannu A, Palrasu M, Shanmugasundaram A, Kuppusamy M (2014) Synthesis of 4-methyl-N′-(3-alkyl-2r,6c-diarylpiperidin-4-ylidene)-1,2,3-thiadiazole-5-carbohydrazides with antioxidant, antitumor and antimicrobial activities. Org Biomol Chem 12:5911–5921

    Article  CAS  PubMed  Google Scholar 

  16. Lin CC, Hsieh TH, Liao PY, Liao ZY, Chang CW (2014) Practical synthesis of N-substituted cyanamides via tiemann rearrangement of amidoximes. Org Lett 16:892–895

    Article  CAS  PubMed  Google Scholar 

  17. Li Y, Jian L, Dedou Z, Hui L, Hu Z; Preparation of novel oxime derivative and its application as agricultural fungicide. CN112624965A. 2012 April 9

  18. Kallury RKMR, Rao PLKM (1977) Electron impact studies of some aryl heteryl ketoximes. Org Mass Spectrom 12(6):411–415

    Article  CAS  Google Scholar 

  19. Dornow A, Jordan HD, Muller A (1961) Aliphatic nitro compounds. XXI. The preparation of α-​chloroöximes from nitroölefins. Chem Ber 94:67–76

    Article  CAS  Google Scholar 

  20. Dutkiewicz Z, Mikstacka R (2018) Structure-based drug design for cytochrome P450 family 1 ınhibitors. Bioinorg Chem Appl 1–21

  21. Yim S-K, Kim K, Chun S, Oh T, Jung W et al (2013) Screening of human CYP1A2 and CYP3A4 inhibitors from seaweed in silico and in vitro. Mar Drugs 18:603

    Article  Google Scholar 

  22. Schäfer RJB, Monaco MR, Tirla LM, A, Rivera-Fuentes P, Wennemers H, (2019) The bioorthogonal isonitrile–chlorooxime ligation. J Am Chem Soc 141:18644–18648

    Article  PubMed  Google Scholar 

  23. Tran NC, Dhondt H, Flipo M, Deprez B, Willand N (2015) Synthesis of functionalized 2-isoxazolines as three-dimensional fragments for fragment-based drug discovery. Tetrahedron Lett 56:4119–4123

    Article  CAS  Google Scholar 

  24. Exner O, Motekov N (1982) Configuration and conformation of amidoximes. N. N-Dialkyl derivatives Collect Czechoslov Chem Commun 47:814–827

    Article  CAS  Google Scholar 

  25. Okecha SA (1979) Reactions of N, N, S, S’-tetramethyldithiocarbamidium iodide. Chem Ind-London 15:526

    Google Scholar 

  26. Thipyapong K, Uehara T, Tooyama Y, Braband H, Alberto R, Arano Y (2011) Insight into technetium amidoxime complex: oxo technetium(V) complex of N-substituted benzamidoxime as new basic structure for molecular ımaging. Inorg Chem 50:992–998

    Article  CAS  PubMed  Google Scholar 

  27. Brand-Williams W, Cuvelier ME, Berset C (1995) Use of a free radical method to evaluate antioxidant activity. LWT Food Sci Technol 28:25–30

    Article  CAS  Google Scholar 

  28. Ruch RJ, Cheng SJ, Klaunig JE (1989) Prevention of cytotoxicity and inhibition of intercellular communication by antioxidant catechins isolated from Chinese green tea. Carcinogenesis 10:1003–1008

    Article  CAS  PubMed  Google Scholar 

  29. Trott O, Olson AJ (2010) AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization and multithreading. J Comput Chem 31:455–461

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Hanwell MD, Curtis DE, Lonie DC, Vandermeersch T, Zurek E, Hutchison J (2012) Avogadro: an advanced semantic chemical editor, visualization, and analysis platform. J Cheminform 4:17

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Funding

This study was financially supported by Kocaeli University BAP (FBA-2020–2072 and FYL-2020–2208).

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Authors and Affiliations

  1. Department of Chemistry, Faculty of Arts and Sciences, Kocaeli University, 41380, Umuttepe, İzmit, Kocaeli, Turkey

    Sait Sarı, Nazlıcan Kılıç & Mehmet Yılmaz

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  1. Sait Sarı
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  2. Nazlıcan Kılıç
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  3. Mehmet Yılmaz
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Contributions

Sait Sari: methodology, investigation, experimental studies, data analysis, writing original draft, and in silico studies. Nazlıcan Kılıç: investigation and experimental studies. Mehmet Yilmaz: methodology, data analysis, supervision, writing original draft, and review. Final version of the manuscript submitted was approved by all authors.

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Correspondence to Mehmet Yılmaz.

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Sarı, S., Kılıç, N. & Yılmaz, M. In vitro antioxidant activities and in silico molecular docking studies of N-substituted oxime derivatives. Struct Chem 34, 605–616 (2023). https://doi.org/10.1007/s11224-022-01978-0

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  • DOI: https://doi.org/10.1007/s11224-022-01978-0

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