Synthesis and docking analysis of new heterocyclic system of tetrazolo[5',1':2,3][1,3,4]thiadiazepino [7,6-b]quinolines as aldose reductase inhibitors

Document Type: Original Article

Authors

1 Department of Chemistry, School of Sciences, Ferdowsi University of Mashhad, Mashhad, Iran

2 Immunology Research Center, Avicenna Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran

Abstract

Objective(s):In recent years, the chemistry of Tetrazolo[5',1':2,3][1,3,4]thiadiazepino [7,6-b]quinolines have received considerable attention owing to their synthetic and effective biological importance which exhibits a wide variety of biological activity. As the inhibitor of aldose reductase, the aforementioned compounds may have implication in preventing complications of diabetes.
Materials and Methods: A group of tetrazolo[5',1':2,3][1,3,4]thiadiazepino [7,6-b]quinolinederivatives were synthesized, and theoretically evaluated for their inhibitory potency against aldose reductase (ALR) via docking process. The docking calculation was done in Genetic Optimization for Ligand Docking (GOLD) 5.2 software using Genetic algorithm.
Results: Compounds 3a and 3f showed the best inhibitory potency by GOLD score value of 78.83 and 76.88 respectively.
Conclusion: All of the best models formed strong hydrogen bonds with Trp 111 and Tyr 209 via tetrazole moiety. It was found that pi-pi interaction between Tyr 209, Trp 20 and His 110 side chain and quinolin moiety was one of the common factors in enzyme-inhibitor junction. It was found that both hydrogen bonding and hydrophobic interactions are important in the structure and function of biological molecules, especially for inhibition in a complex.

Keywords


1. Gasteiger E, Gattiker A, Hoogland C, Ivanyi I, Appel R, Bairoch A. ExPASy: The proteomics server for in-depth protein knowledge and analysis. Nucleic Acids Res 2003; 31:3784-3788.

2. Oates PJ. Polyol pathway and diabetic peripheral neuropathy. Int Rev Neurobiol 2002; 50:325-392.

3. Bohren K, Grimshaw C, Lai C, Harrison D, Ringe D, Petsko G, et al. Tyrosine-48 is the proton donor and histidine-110 directs substrate stereochemical selectivity in the reduction reaction of human aldose reductase: enzyme kinetics and crystal structure of the Y48H mutant enzyme. Biochemistry 1994; 33:2021-2032.

4. Grimshaw CE, Bohren KM, Lai CJ, Gabbay KH. Human aldose reductase: pK of tyrosine 48 reveals the preferred ionization state for catalysis and inhibition. Biochemistry 1995; 34:14374-14384.

5. Petrash, J. All in the family: aldose reductase and closely related aldo-keto reductases. Cell Mol Life Sci 2004; 61:737–749.

6. Krovat EM, Steindl T, Lange T. Recent advance in docking and scoring. Curr Comput Aided Drug Des 2005; 1:93-102.

7. Girija CR, Karunakar P, Poojari CS, Begum NS, Syed AA. Molecular docking studies of curcumin derivatives with multiple protein targets for procarcinogen activating enzyme inhibition. J Proteomics Bioinform 2010; 3:200-203.

8. Elderfield RC. Heterocyclic compounds. New York: John-Wiley & Sons; 1960.

9. Delgado JN, Remers WA. Wilson and Gisvold’s Text Book of Organic Medicinal and Pharmaceutical Chemistry. 10 th ed. Philadelphia: Lippincott Williams & Wilkins; 1998.

10. Nicolaou KC, Gross JL, Kerr MA. Synthesis of novel heterocycles related to the dynemicin a ring skeleton.  J  Heterocycl Chem 1996; 33:735-746.

11. Bringmann G, Reichert Y, Kane VV. The total synthesis of streptonigrin and related antitumor antibiotic natural products. Tetrahedron 2004; 60:3539-3574.

12. Sangu K, Fuchibe K, Akiyama T. A Novel approach to 2-arylated quinolines: electrocyclization of alkynyl imines via vinylidene complexes. Org Lett 2004; 6:353-355.

13. Crousse B, Bégué JP, Bonnet Delpon D. Synthesis of tetrahydroquinoline derivatives from CF3-N-arylaldimine and vinyl ethers. Tetrahedron Lett 1998; 39: 5765-5768.

14. Crousse B, Bégué JP, Bonnet Delpon D. Synthesis of 2-CF3-tetrahydroquinoline and quinoline derivatives from CF3-N-Arylaldimine. J Org Chem 2000; 65:5009-5013. 

15. Fournet A, Barrios AA, Muñoz V, Hocquemiller R, Cavé A, Richomme P, et al. Substituted quinoline alkaloids as potential antileishmanial drugs. Antimicrob Agents Chemother 1993; 37:859-863.

16. Wright CW, Addae Kyereme J, Breen AG, Brown JE, Cox MF, Croft SL, et al. Synthesis and evaluation of cryptolepine analogues for their potential as new antimalarial agents. J Med Chem 2001; 44:3187-3194.

17. Nicolaou KC, Gross JL, Kerr MA. Synthesis of novel heterocycles related to the dynemicin a ring skeleton.  J Heterocycl Chem 1996; 33:735-746.

18. Bringmann G, Reichert Y, Kane V. The total synthesis of streptonigrin and related antitumor antibiotic natural products. Tetrahedron 2004; 60:3539-3574.

19. Chiari E, Oliveira AB, Prado MAF, Alves RJ, Galvão LMC, Araujo FG. Potential use of WR6026 as prophylaxis against transfusion-transmitted American trypanosomiasis. Antimicrob Agents Chemother 1996; 40:613-615.

20. Bekhit AA, El Sayed OA, Aboulmagd E, Park JY. Tetrazolo[1,5-a]quinoline as a potential promising new scaffold for the synthesis of novel anti-inflammatory and antibacterial agents. Eur J Med Chem 2004; 39:249-255.

21. Iranshahi M, Jabbari A, Orafaie A, Mehri R, Zeraatkar S, Ahmadi T, et al. Synthesis and SAR studies of mono O-prenylated coumarins as potent 15-lipoxygenase inhibitors. Eur J Med Chem 2012; 57:134-142.

22. Jabbari A, Davoodnejad M, Alimardani M, Assadieskandar A, Sadeghian A, Safdari H, et al. Synthesis and SAR studies of 3-allyl-4-prenyloxyaniline amides as potent 15-lipoxygenase inhibitors. Bioorg Med Chem 2012; 20:5518-5526.