Indian Journal of Drugs and Diseases

Open Access Open Access  Restricted Access Subscription Access

Molecular Docking of some Herbal-based Potential Anti-psoriasis Agents with Dihydrofolate Reductase


Affiliations
1 Department of Biological Sciences, MB Khalsa College, Indore, MP, India
2 Department of Biotechnology, Christian Eminent College, Indore, MP, India, India
3 School of Biochemistry, DAVV, Indore, MP, India
4 Department of Biochemistry, Index Medical College, Indore, MP, India
 

Objectives: To find out the herbal inhibitor for Dihydrofolate reductase (DHFR) in replacements of some existing drugs like methotrexate to reduce side effects in psoriasis and also to cure psoriasis. Methods: Computational simulation techniques are used for molecular docking of few herbals like beta-santalol, quercetin, carvacrol, curcumin and ferulic acid into DHFR by using AutoDock 4.0. Online tool and databases like Qsite-finder, PDB, and Chemspider are also used to retrieve active sites and 3D structures of enzymes and inhibitors. Parameters like binding energy, intermolecular energy, inhibition constant and H-bonding between ligands and target are used to determine extent of inhibition. Results: This information could be supportive for new drug design for psoriasis, in which these potential inhibitors should interact strongly with above mentioned residues. In our study on the basis of minimum binding energy and inhibition constant we concluded that β-santalol was found to be best. β-Santalol interacted with DHFR and gives minimum binding energy - 6.85 Kcal/mol and inhibition constant 9.48 µm, it is also formed two H-bond with the active site residue Tyr121 of the DHFR. As this study utilized herbals which are unique with respect to inhibit DHFR and it could be better prospect on for methotrexate which is responsible for side effects if alone is used. This is the important initiation to in utilization of herbals for such target inhibition. Conclusion: DHFR is an enzyme that reduces dihydrofolic acid to tetrahydrofolic acid, using NADPH as electron donor. Tetrahydrofolate and its derivatives are essential for purine synthesis, which are important for cell proliferation and cell growth Therefore these herbals will block the reduction of dihydrofolic acid to tetrahydrofolic acid and inhibit the synthesis of nucleic acid precursor in not only psoriasis but in other such disease as well.

Keywords

Psoriasis, DHFR, Herbal Inhibitors, Drug Designing, Docking
User
Notifications

  • Duvic M, Asano A and Hagar C (1998) The pathogenesis of psoriasis and the mechanism of action of Tazaroter. J. American Academy of Dermatol.4,129-133.

  • Schwartz PM, Barnkett SK, Atillasoy ES and Milstone LM (1992) Methotrexate induces differentiation of human keratinocytes Proceedings of the National Academy of Sciences.89, 594-598.

  • Kristian Reich and Ulrich Mrowietz (2007) Treatment goals in psoriasis. J.der Deutschen Dermatologischen Gesellschaft. 5, 566-574

  • Ikram H, Salah EB and Adel K (2011) Binding affinities and protein ligand complex geometries of some quinolylaryl α, β- unsaturated ketones. J. Health Sci. 57(5), 397-400

  • Jordan P, Volpato Brahm J, Yachnin, Jonathan Blanchet, Vanessa Guerrero, Lucie Poulin, Elena Fossati, Albert M Berghuis, and Joelle NP (2009) Multiple conformers in active site of human dihydrofolate reductase F31R/Q35E Double Mutant Suggest Structural Basis for Methotrexate Resistance. J. Biol. Chem. 24, 20079-20089.

  • Slamon DJ, Romond EH and Perez EA (2006) Advances in adjuvant therapy for breast cancer. Clin. Adv. Hematological Oncol. 4, 4-9.

  • Subramanian S and Bernard T (1978) Interaction of methotrexate, folates, and pyridine nucleotides with dihydrofolate reductase: Calorimetric and spectroscopic binding studies. Proceedings of the National Academy of Sciences.75, 3201-3205.

  • Strojan P, Soba E, Budihna M and Auersperg (2005) Radiochemotherapy with Vinblastine, Methotrexate, and Bleomycin in the treatment of verrucous carcinoma of the head and neck. J. Surg. Oncol. 92, 278-283

  • Ramanan AV, Whitworth P and Baildam EM (2003) Use of methotrexate in juvenile idiopathic arthritis. Arch. Dis.Childhood.88, 197-200

  • Takemura Y, Kobayashi H and Miyachi H (1999) Variable expression of the folylpolyglutamate synthetase gene at the level of mRNA transcription in human leukemia cell lines sensitive, or made resistant, to various antifolate drugs. Anticancer Drugs.10,677-683

  • Vivian Cody, Jim Pace and Jennifer Makinl (2009) Correlations of inhibitor kinetics for Pneumocystis jirovecii and human dihydrofolate reductase with structural data for human active site mutant enzyme complexes. Biochemistry NIH Public Access. 3; 48(8),1702-1711.

  • Vivian Cody, Jim Pace and Jennifer Makinl (2010) Structural analysis of Pneumocystis carinii and human DHFR complexes with NADPH and a series of five potent 6-[500-(x-carboxyalkoxy)benzyl]- pyrido[2,3-d] pyrimidine derivatives. Acta Crystallographica Section D Biological Crystallography. (67D) ISSN 0907-4449, 1-7.

  • Cole JC, Murray CW, Nissink JW, Taylo RD and Taylor R (2005) Comparing protein-ligand docking programs are difficult. Proteins. 60,325-332.

  • Morris GM, Goodsell DS, Halliday RS, Huey R, Hart WE, Belew RK and Olson AJ (1998) Automated docking using a lamarckian genetic algorithm and an empirical binding free energy function. J. Computational Chem. 19, 1639-1662.

  • Uthaman Gowthaman, Mannu Jayakanthan, Durai Sundar (2008) Molecular docking studies of dithionitrobenzoic acid and its related compounds to protein disulfide isomerase computational screening of inhibitors to HIV-1 entry, BMC Bioinformatics. http:// www.biomedcentral.com/1471-2105/9/S12/S14, 9(Suppl 12):S14 doi:10.1186/1471-2105-9-S12-S14

  • www.chemspider.com

  • Protein Data Bank (http://www.rcsb.org/pdb/home/home.do)

  • http://bmbpcu36.leeds.ac.uk/qsitefinder/help.html


Abstract Views: 423

PDF Views: 474




  • Molecular Docking of some Herbal-based Potential Anti-psoriasis Agents with Dihydrofolate Reductase

Abstract Views: 423  |  PDF Views: 474

Authors

A. Kelotra
Department of Biological Sciences, MB Khalsa College, Indore, MP, India
V. G. Soumya
Department of Biological Sciences, MB Khalsa College, Indore, MP, India
S. Kelotra
Department of Biotechnology, Christian Eminent College, Indore, MP, India, India
S. M. Gokhale
School of Biochemistry, DAVV, Indore, MP, India
A. K. Bidwai
Department of Biochemistry, Index Medical College, Indore, MP, India

Abstract


Objectives: To find out the herbal inhibitor for Dihydrofolate reductase (DHFR) in replacements of some existing drugs like methotrexate to reduce side effects in psoriasis and also to cure psoriasis. Methods: Computational simulation techniques are used for molecular docking of few herbals like beta-santalol, quercetin, carvacrol, curcumin and ferulic acid into DHFR by using AutoDock 4.0. Online tool and databases like Qsite-finder, PDB, and Chemspider are also used to retrieve active sites and 3D structures of enzymes and inhibitors. Parameters like binding energy, intermolecular energy, inhibition constant and H-bonding between ligands and target are used to determine extent of inhibition. Results: This information could be supportive for new drug design for psoriasis, in which these potential inhibitors should interact strongly with above mentioned residues. In our study on the basis of minimum binding energy and inhibition constant we concluded that β-santalol was found to be best. β-Santalol interacted with DHFR and gives minimum binding energy - 6.85 Kcal/mol and inhibition constant 9.48 µm, it is also formed two H-bond with the active site residue Tyr121 of the DHFR. As this study utilized herbals which are unique with respect to inhibit DHFR and it could be better prospect on for methotrexate which is responsible for side effects if alone is used. This is the important initiation to in utilization of herbals for such target inhibition. Conclusion: DHFR is an enzyme that reduces dihydrofolic acid to tetrahydrofolic acid, using NADPH as electron donor. Tetrahydrofolate and its derivatives are essential for purine synthesis, which are important for cell proliferation and cell growth Therefore these herbals will block the reduction of dihydrofolic acid to tetrahydrofolic acid and inhibit the synthesis of nucleic acid precursor in not only psoriasis but in other such disease as well.

Keywords


Psoriasis, DHFR, Herbal Inhibitors, Drug Designing, Docking

References