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A comparative study on the druggability of Schiff bases and dithiocarbamate derivatives of chitosan

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Abstract

The druggability of the Schiff bases and dithiocarbamate derivatives of chitosan was examined; the oral bioavailability and bioactivity of all these molecules against selected drug targets were investigated, as well as ADME/Tox studies were conducted. It was observed that the Lipinski’s rule of five was satisfied by all the molecules. The Schiff bases and dithiocarbamate derivatives of chitosan also show good bioactivity score for protease and enzyme inhibition. The ADME/Tox studies conducted show that almost all the derivatives are free from toxicity risks, except citral- and sulfur-containing derivatives. Substitution of the –SH group by –NH2 gives better positive results in toxicology studies. From this study, it has been observed that these molecules exhibit fairly good drug score and are orally viable molecules. The mechanism driving their bioactivity might be chelation of chitosan and its derivatives with essential metal ions. Chitosan and the derivatives studied can serve as good lead molecules for further research.

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Abbreviations

C:

Chitosan

CC:

Chitosan Schiff base of citral

CnC:

Chitosan Schiff base of cinnamaldehyde

DC:

Dithiocarbamate derivatives of chitosan

DFT:

Density functional theory

GC:

Chitosan Schiff base of glyoxylic acid

GPCR:

G protein-coupled receptors

HC:

Chitosan Schiff base of heptaldehyde

PaC:

Chitosan Schiff base of pyruvic acid

PC:

Chitosan Schiff base of pyridoxal hydrochloride

PcC:

Chitosan Schiff base of 2-pyridine carbaldehyde

PSA:

Polar surface area

SC:

Chitosan Schiff base of salicylaldehyde

SMILES:

Simplified molecular-input line-entry system

References

  1. Lahlou M, (2013) The success of natural products in drug discovery. Pharmacol. Pharmacy 417–31

  2. Mohamed NA, Sabaa MW, El-Ghandour AH, Abdel-Aziz MM, Abdel-Gawad OF (2013) Quaternized N-substituted carboxymethyl chitosan derivatives as antimicrobial agents. Int J Bio Macromol 60:156–164

    Article  CAS  Google Scholar 

  3. Xia W, Liu P, Zhang J, Chen J (2011) Biological activities of chitosan and chitooligosaccharides. Food Hydrocoll 25:170–179

    Article  CAS  Google Scholar 

  4. Kim SK, Rajapakse N (2005) Enzymatic production and biological activities of chitosan oligosaccharides (COS): a review. Carbohydr Polym 62:357–368

    Article  CAS  Google Scholar 

  5. Lim SH, Hudson SM (2003) Review of chitosan and its derivatives as antimicrobial Agents and their uses as textile chemicals. J Macromol Sci C 43:223–269

    Article  Google Scholar 

  6. Li DH, Liu LM, Tian KL, Liu JC, Fan XQ (2007) Synthesis, biodegradability and cytotoxicity of water-soluble isobutylchitosan. Carbohydr Polym 67:40–45

    Article  CAS  Google Scholar 

  7. Zhao D, Huang J, Hu S, Mao J, Mei L (2011) Biochemical activities of N, O-carboxymethyl chitosan from squid cartilage. Carbohydr Polym 85:832–837

    Article  CAS  Google Scholar 

  8. Shelma R, Sharma CP (2011) Development of lauroyl sulfated chitosan for enhancing hemocompatibility of chitosan. Coll surf B 84:561–570

    Article  CAS  Google Scholar 

  9. de Britto D, Assis OBG (2007) A novel method for obtaining a quaternary salt of chitosan. Carbohydr Polym 69:305–310

    Article  Google Scholar 

  10. Yang J, Cai J, Hu Y, Li D, Du Y (2012) Preparation, characterization and antimicrobial activity of 6-amino-6-deoxychitosan. Carbohydr Polym 87:202–209

    Article  CAS  Google Scholar 

  11. Peng Y, Han B, Liu W, Xu X (2005) Preparation and antimicrobial activity of hydroxypropyl chitosan. Carbohydr Res 340:1846–1851

    Article  CAS  Google Scholar 

  12. Jin X, Wang J, Bai J (2009) Synthesis and antimicrobial activity of the Schiff base from chitosan and citral. Carbohydr Res 344:825–829

    Article  CAS  Google Scholar 

  13. Guo Z, Xing R, Liu S, Zhong Z, Ji X, Wang L (2007) Antifungal properties of Schiff bases of chitosan, N-substituted chitosan and quaternized chitosan. Carbohydr Res 342:1329–1332

    Article  CAS  Google Scholar 

  14. Kajal A, Bala S, Kamboj S, Sharma N, Saini V (2013) Schiff bases: a versatile pharmacophore. J Catalysts, Article ID 893512

  15. Kumar S, Dhar DN, Saxena PN (2009) Application of metal complexes of schiff bases-a review. J Sci Ind Res 68:181–187

    CAS  Google Scholar 

  16. Przybylski PHA, Pyta K, Brzezinski B, Bartl F (2009) Biological properties of schiff bases and azo derivatives of phenols. Curr Org Chem 13:124

    Article  CAS  Google Scholar 

  17. da Silva CM, da Silva DL, Modolo LV, Alves RB, de Resende MA, Martins CVB (2011) Schiff bases: a short review of their antimicrobial activities. J Adv Res 2:1–8

    Article  Google Scholar 

  18. Tirkistani FAA (1998) Thermal analysis of some chitosan Schiff bases. Poly Degrad Stab 60:67–70

    Article  CAS  Google Scholar 

  19. dos Santos JE, Dockal ER, Cavalheiro ÉTG (2005) Synthesis and characterization of Schiff bases from chitosan and salicylaldehyde derivatives. Carbohydr Polym 60:277–282

    Article  Google Scholar 

  20. Dash M, Chiellini F, Ottenbrite RM, Chiellini E (2011) Chitosan—a versatile semi- synthetic polymer in biomedical Applications. Progr Polym Sci 36:981–1014

    Article  CAS  Google Scholar 

  21. Alexandra Mu˜noz-Bonilla, Marta Fernández-García (2012) Polymeric materials with antimicrobial activity. Progr Polym Sci 37:281–339

  22. Sharma A (2012) Extraction of lead by dithiocarbmate derivative of chitosan. Int J Chem Environm Pharmaceut Res 3:170–173

    CAS  Google Scholar 

  23. Qin Y, Liu S, Xing R, Yu H, Li K, Meng X, Li R, Li P (2012) Synthesis and characterization of dithiocarbamate chitosan derivatives with enhanced antifungal activity. Carbohydr Polym 89:388–393

    Article  CAS  Google Scholar 

  24. Frisch MJ et al (2004) Gaussian 03. Revision C02. Gaussian, Inc, Wallingford CT

  25. Becke AD (1993) Density functional thermochemistry. III. The role of exact exchange. J Chem Phys 98:5648–5652

    Article  CAS  Google Scholar 

  26. Lee C, Yang W, Parr RG (1988) Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density. Phys Rev B 37:785–789

    Article  CAS  Google Scholar 

  27. Hehre WJ, Ditchfield R, Pople JA (1972) Self-consistent molecular orbital methods. XII. Further extensions of Gaussian-type Basis sets for use in molecular orbital studies of organic molecules. J Chem Phy 56:2257–2261

    Article  CAS  Google Scholar 

  28. Weininger D (1988) SMILES, a chemical language and information system. 1. Introduction to methodology and encoding rules. J Chem Infor Comp Sci 28:31–36

    Article  CAS  Google Scholar 

  29. http://www.molecularnetworks.com

  30. O’Boyle NM, Banck M, James CA, Morley C, Vandermeersch T, Hutchison GR (2011) Open Babel: an open chemical toolbox. J Cheminform 3:33

    Article  Google Scholar 

  31. http://www.molinspiration.com/cgi-bin/properties

  32. http://www.organic-chemistry.org/prog/peo/

  33. Lipinski CA, Lombardo F, Dominy BW, Feeney PJ (2001) Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Delivery Rev 46:3–26

    Article  CAS  Google Scholar 

  34. Veber DF, Johnson SR, Cheng HY, Smith BR, Ward KW, Kopple KD (2002) Molecular properties that influence the oral bioavailability of drug candidates. J Med Chem 45:2615–2623

    Article  CAS  Google Scholar 

  35. Ertl P, Rohde B, Selzer P (2000) Fast calculation of molecular polar surface area as a sum of fragment-based contributions and its application to the prediction of drug transport properties. J Med Chem 43:3714–3717

    Article  CAS  Google Scholar 

  36. Verma A (2012) Lead finding from phyllanthus debelis with hepatoprotective potentials. Asian Pacific J Tropical Biomed 2:S1735–S7

  37. Zhao YH, Abraham MH, Le J, Hersey A, Luscombe CN, Beck G et al (2002) Rate-limited steps of human oral absorption and QSAR studies. Pharmaceut Res 19:1446–1457

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Chemistry, University of Calicut, Malappuram, 673635, India

    T. Noushad, P. Alikutty, H. Basila, Vijisha K. Rajan, K. Muraleedharan & V. M. Abdul Mujeeb

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  1. T. Noushad
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  2. P. Alikutty
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  3. H. Basila
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  4. Vijisha K. Rajan
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  5. K. Muraleedharan
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  6. V. M. Abdul Mujeeb
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Correspondence to V. M. Abdul Mujeeb.

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Noushad, T., Alikutty, P., Basila, H. et al. A comparative study on the druggability of Schiff bases and dithiocarbamate derivatives of chitosan. Polym. Bull. 73, 2165–2177 (2016). https://doi.org/10.1007/s00289-016-1601-y

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  • DOI: https://doi.org/10.1007/s00289-016-1601-y

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