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Research Article

3-Benzyl(phenethyl)-2-thioxobenzo[g]quinazolines as a new class of potent α-glucosidase inhibitors: synthesis and molecular docking study

    Rashad Al-Salahi

    Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, PO box 2457, Riyadh 11451, Saudi Arabia

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    ,
    Rohaya Ahmad

    Faculty of Applied Sciences, Universiti Teknologi MARA, 40450 shah Alam, Selangor Darul Ehsan, Malaysia

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    ,
    ElHassane Anouar

    Department of Chemistry, College of Science & Humanities, Prince Sattam bin Abdulaziz University, PO Box 83, Al Kharj 11942, Saudi Arabia

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    ,
    Nor Izzati Iwana Nor Azman

    Faculty of Applied Sciences, Universiti Teknologi MARA, 40450 shah Alam, Selangor Darul Ehsan, Malaysia

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    ,
    Mohamed Marzouk

    Department of Chemistry, College of Science & Humanities, Prince Sattam bin Abdulaziz University, PO Box 83, Al Kharj 11942, Saudi Arabia

    Chemistry of Natural Products Group, Center of Excellence for Advanced Sciences, National Research Centre, Dokki, Cairo 12622, Egypt

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    &
    Hatem A Abuelizz

    *Author for correspondence: Tel.: +966 114 677 194;

    E-mail Address: Habuelizz@ksu.edu.sa

    Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, PO box 2457, Riyadh 11451, Saudi Arabia

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    Published Online:8 Jun 2018https://doi.org/10.4155/fmc-2018-0141

    Abstract

    Aim: Using a simple modification on a previously reported synthetic route, 3-benzyl(phenethyl)-2-thioxobenzo[g]quinazolin-4(3H)-ones (1 and 2) were synthesized with high yields. Further transformation of 1 and 2 produced derivatives 3-26, which were structurally characterized based on NMR and MS data, and their in vitro α-glucosidase inhibitory activity was evaluated using Baker's yeast α-glucosidase enzyme. Results: Compounds 2, 4, 8, 12 and 20 exhibited the highest activity (IC50 = 69.20, 59.60, 49.40, 50.20 and 83.20 μM, respectively) compared with the standard acarbose (IC50 = 143.54 μM). Conclusion: A new class of potent α-glucosidase inhibitors was identified, and the molecular docking predicted plausible binding interaction of the targets in the binding pocket of α-glucosidase and rationalized the structure–activity relationship (SARs) of the target compounds.

    Papers of special note have been highlighted as: • of interest; •• of considerable interest

    References

    • 1 Babar A, Yar M, Tarazi H et al. Molecular docking and glucosidase inhibition studies of novel N-arylthiazole-2-amines and ethyl 2-[aryl(thiazol-2-yl) amino] acetates. Med. Chem. Res. 26, 3247–3261 (2017).
      CASGoogle Scholar
    • 2 Zhen J, Dai Y, Villani T, Giurleo D, Simon JE, Wu Q. Synthesis of novel flavonoid alkaloids as α-glucosidase inhibitors. Bioorg. Med. Chem. 25, 5355–5364 (2017).
      Medline CASGoogle Scholar
    • 3 Spasov AA, Babkov DA, Prokhorova TY et al. Synthesis and biological evaluation of 2-acylbenzofuranes as novel α-glucosidase inhibitors with hypoglycemic activity. Chem. Biol. Drug Des. 90, 1184–1189 (2017).
      Medline CASGoogle Scholar
    • 4 Iqbal S, Khan MA, Javaid K et al. New carbazole linked 1,2,3-triazoles as highly potent non-sugar α-glucosidase inhibitors. Bioorg. Chem. 74, 72–81 (2017).
      Medline CASGoogle Scholar
    • 5 Zhang AJ, Rimando AM, Mizuno CS, Mathews ST. α-Glucosidase inhibitory effect of resveratrol and piceatannol. J. Nutr. Biochem. 47, 86–93 (2017).
      Medline CASGoogle Scholar
    • 6 Wang G, Peng Y, Xie Z, Wang J, Chen M. Synthesis, α-glucosidase inhibition and molecular docking studies of novel thiazolidine-2,4-dione or rhodanine derivatives. Med. Chem. Commun. 8, 1477–1484 (2017).
      CASGoogle Scholar
    • 7 Xie Z, Wang G, Wang J et al. Synthesis, biological evaluation, and molecular docking studies of novel isatin-thiazole derivatives as α-glucosidase inhibitors. Molecules 22(4), 659 (2017).
      Google Scholar
    • 8 Gong Z, Peng Y, Qiu J, Cao A, Wang G, Peng Z. Synthesis in vitro α-glucosidase inhibitory activity and molecular docking studies of novel benzothiazole-triazole derivatives. Molecules 22(9), 1555 (2017).
      Google Scholar
    • 9 Kasturi S, Surarapu S, Bathoju CC et al. Synthesis, molecular modeling and biological evaluation of azaflavanonesas α-glucosidase inhibitors. Med. Chem. Commun. 8, 1618–1630 (2017).
      CASGoogle Scholar
    • 10 Taha M, Rahim F, Imran S et al. Synthesis, α-glucosidase inhibitory activity and in silico study of tris-indole hybrid scaffold with oxadiazole ring: as potential leads for the management of Type-II diabetes mellitus. Bioorg. Chem. 74, 30–40 (2017).
      Medline CASGoogle Scholar
    • 11 Barakat A, Ali M, Mohammed AA et al. Synthesis of thiobarbituric acid derivatives: in vitro α-glucosidase inhibition and molecular docking studies. Bioorg. Chem. 75, 99–105 (2017).
      Medline CASGoogle Scholar
    • 12 Liu Z, Ma S. Recent advances in synthetic α-glucosidase inhibitors. ChemMedChem 12, 819–829 (2017).
      Medline CASGoogle Scholar
    • 13 Chaudhry F, Choudhry S, Huma R et al. Hetarylcoumarins: synthesis and biological evaluation as potent α-glucosidase inhibitors. Bioorg. Chem. 73, 1–9 (2017).
      Medline CASGoogle Scholar
    • 14 Salar U, Taha M, Khan KM et al. Syntheses of new 3-thiazolyl coumarin derivatives, in vitro α-glucosidase inhibitory activity, and molecular modeling studies. Eur. J. Med. Chem. 122, 196–204 (2016).
      Medline CASGoogle Scholar
    • 15 Zhang Y, Gao H, Liu R et al. Quinazoline-1-deoxynojirimycin hybrids as high active dual inhibitors of EGFR and α-glucosidase. Bioorg. Med. Chem. Lett. 27, 4309–4313 (2017).
      Medline CASGoogle Scholar
    • 16 Wang G, Wang J, He D, Li X, Li J, Peng Z. Synthesis and biological evaluation of novel 1,2,4-triazine derivatives bearing carbazole moiety as potent α-glucosidase inhibitors. Bioorg. Med. Chem. Lett. 26, 2806–2809 (2016).
      Medline CASGoogle Scholar
    • 17 Gurram V, Garlapati R, Thulluri C et al. Design, synthesis, and biological evaluation of quinazoline derivatives as α-glucosidase inhibitors. Med. Chem. Res. 24, 2227–2237 (2015).
      CASGoogle Scholar
    • 18 Garlapati R, Pottabathini N, Gurram V et al. Development of α-glucosidase inhibitors by room temperature C-C cross-couplings of quinazolinones. Org. Biomol. Chem. 11, 4778–4791 (2013). • Describes the α-glucosidase inhibition activity of some related quinazoline derivatives.
      Medline CASGoogle Scholar
    • 19 Wei M, Chai WM, Wang R, Yang Q, Deng Z, Peng Y. Quinazolinone derivatives: synthesis and comparison of inhibitory mechanisms on α-glucosidase. Bioorg. Med. Chem. 25, 1303–1308 (2017).
      Medline CASGoogle Scholar
    • 20 Al-Salahi R, Abuelizz HA, Ghabbour HA, El-Dib R, Marzouk M. Molecular docking study and antiviral evaluation of 2-thioxo-benzo[g]quinazolin-4(3H)-one derivatives. Chem. Cent. J. 10, 21 (2016). •• Reports the antiviral activity of some related benzoquinazolines.
      MedlineGoogle Scholar
    • 21 Al-Salahi R, Abuelizz HA, El-Dib R, Marzouk M. Antimicrobial activity of new 2-thioxo-benzo[g]quinazolin-4(3H)-one derivatives. Med. Chem. 13, 85–92 (2017). •• Reports the antimicrobial activity of some benzoquinazoline derivatives.
      CASGoogle Scholar
    • 22 Al-Salahi R, El Dib R, Marzouk M. Synthesis and in vitro cytotoxicity evaluation of new 2-thioxo-benzo[g]quinazolin-4(3H)-one derivatives. Heterocycles 91, 1735–1751 (2015). •• Describes the synthetic methodologies of benzoquinazolines series with cytotoxicity activity.
      CASGoogle Scholar
    • 23 Abuelizz AH, El-Dib RA, Marzouk M, Al-Salahi R. In vitro evaluation of new 2-phenoxy-benzo[g][1,2,4]triazolo[1,5-a]quinazoline derivatives as antimicrobial agents. Microb. Pathog. 117, 60–67 (2018).
      Medline CASGoogle Scholar
    • 24 Ahmad R, Hashim H, Noor Z et al. Antioxidant and antidiabetic potential of Malaysian Uncaria. Res. J. Med. Plant 5, 587–595 (2011).
      Google Scholar
    • 25 Morris GM, Huey R, Lindstrom W et al. AutoDock4 and AutoDockTools4: automated docking with selective receptor flexibility. J. Comput. Chem. 30, 2785–2791 (2009).
      Medline CASGoogle Scholar
    • 26 Tagami T, Yamashita K, Okuyama M, Mori H, Yao M, Kimura A. Molecular basis for the recognition of long-chain substrates by plant alpha-glucosidases. J. Biol. Chem. 288, 19296–19303 (2013).
      Medline CASGoogle Scholar
    • 27 Abuelizz HA, El-Dib RE, Marzouk M et al. Molecular docking and anticonvulsant activity of newly synthesized quinazoline derivatives. Molecules 22, 1094 (2017).
      Google Scholar
    • 28 Satpanthi PS, Trivedi JP. Quinazolines. IV. Synthesis of 2-​alkyl-​3-​alkyl(aralkyl)​aryl-​4(3H)​-​benzo(g)​quinazolinones and 2-​mercapto-​3-​aryl(alkyl)​alkyl-​4(3H)​-​benzo(g)​quinazolinones. J. Indian Chem. Soc. 49, 605–609 (1972). •• Includes the synthesis of benzo[g]quinazoline derivatives.
      CASGoogle Scholar
    • 29 Al-Salahi R, Marzouk M. Synthesis of novel 2-phenoxy-benzo[g][1,2,4]triazolo[1,5-a]quinazoline derivatives starting from diphenyl-N-cyanoimidocarbonate. Russ. J. Gen. Chem. 86, 1741–1746 (2016).
      CASGoogle Scholar
    • 30 Al-Salahi R, Marzouk M, Ghabbour HA, Kun FH. Synthesis of novel 2-(methylthio)-benzo[g][1,2,4]-triazolo[1,5-a]quinazolin-5-(4H)-one and its derivatives. Lett. Org. Chem. 11, 759–767 (2014).
      CASGoogle Scholar