Exploration of the mechanisms of Aflatoxin B1 toxicity and the targets of Oltipraz by reverse docking

doi:10.5246/jcps.2014.03.024

Journal of Chinese Pharmaceutical Sciences

• Original articles • Previous Articles Next Articles

Exploration of the mechanisms of Aflatoxin B1 toxicity and the targets of Oltipraz by reverse docking

Yu Zhang, Limei Guo^*

Department of Pathology, School of Basic Medical Science, Peking University Health Science Center, Beijing 100191, China

Received:2013-11-19 Revised:2013-12-06 Online:2014-03-13 Published:2013-12-25
Contact: *Corresponding author. Tel.: 86-10-82802561; E-mail: guolimei@bjmu.edu.cn
About author:*Corresponding author. Tel.: 86-10-82802561; E-mail: guolimei@bjmu.edu.cn

Abstract

Abstract:

Aflatoxin B1 toxicity is well known but the mechanism of this toxicity is still unclear. In addition, the target of the anti-aflatoxin chemopreventive drug Oltipraz remains to be identified. In this study, we employed computer aided reverse docking analysis to identify putative targets of Aflatoxin B1 (AFB) and Oltipraz. The results showed that the clinically known toxic effects of AFB are related to this molecule’s strong binding affinity for key proteins involved in cell apoptosis, hormone metabolism,immune suppression, and digestive organ function. In addition, virtual binding assay indicated that Oltipraz neutralizes the toxicity of AFB by inhibiting its biotransformation enzymes. In conclusion, the technique of reverse docking may be used to identify the specific targets of AFB and Oltipraz, and our findings could significantly accelerate the mechanistic studies of the two molecules and provide guidance for the development of anti-AFB drugs.

Key words: Reverse docking, Aflatoxin B1, Oltipraz

CLC Number:

R962.1

Supporting:

Yu Zhang, Limei Guo. Exploration of the mechanisms of Aflatoxin B1 toxicity and the targets of Oltipraz by reverse docking[J]. Journal of Chinese Pharmaceutical Sciences, DOI: 10.5246/jcps.2014.03.024.

References

[1] Liu, Y.; Chang, C.C.; Marsh. G.M.; Wu, F. Eur. J. Cancer. 2012, 48, 2125–2136.

[2] Williams, J.H.; Phillips, T.D.; Jolly, P.E. Am. J. Clin. Nutr. 2004, 80, 1106–1122.

[3] IARC. Monographs on the Evaluation of Carcinogenic Risks to Humans. 2002, 82, 171–300.

[4] Sparks, D.L.; Woeltz, V.M.; Markesbery, W.R. Arch. Neurol. 1991, 48, 718.

[5] Liu, D.L.; Yao, D.S.; Liang, R. Foreign Medical Sciences (Section Hygiene). 1998, 25, 9–11.

[6] Wang, J.S.; Shen, X.; He, X.; Zhu, Y.R.; Zhang, B.C.; Wang, J.B. J. Natl. Cancer Inst. 1999, 91, 347–354.

[7] Kerstin, G.S.; David, L.E. Toxicology. 2012, 299, 69–79.

[8] Chen, Y.Z.; Zhi, D.G. Proteins. 2001, 42, 217–226.

[9] Liu, X.F.; Ouyang, S.S.; Yu, B.; Huang, K.; Liu, Y.B.; Jiang, H.L. Nucl. Acids Res. 2010, 38, 609–614.

[10] Liu, X.F.; Jiang, H.L.; Li, H.L. J. Chem. Inf. Model. 2011, 51, 2372–2385.

[11] Lu, W.Q.; Liu, X.F.; Cao, X.W.; Xue, M.Z. J. Med. Chem. 2011, 54, 3564–3574.

[12] Gong, J.Y.; Cai, C.Q.; Liu, X.F. Bioinformatics. 2013, 29, 1827–1829.

[13] Kinnings, S.L.; Jackson, R.M. J. Chem. Inf. Model. 2011, 51, 624–634.

[14] Sidi, S.; Sanda, T.; Kennedy, R.D.; Hagen, A.T. Cell. 2008, 133, 864–877.

[15] Harbour, J.W.; Luo, R.X. Cell. 1999, 98, 859–869.

[16] Okuda, M.; Horn, H.F.; Tarapore, P.; Tokuyama, Y. Cell. 2000, 103, 127–140.

[17] Saris, C.J.; Domen, J.; Berns, A. EMBO. 1991, 10, 655–664.

[18] Rustemeyer, S.M.; Lamberson, W.R.; Ledoux, D.R. J. Anim. Sci. 2011, 89, 916–925.

[19] Shuaib, F.M.; Ehiri, J.; Abdullahi, A.; Williams, J.H.; Jolly, P.E. Reprod. Toxicol. 2010, 29, 262–270.

[20] Kahn, S.M.; Nakhla, A.M.; Hryb, D.J.; Rosner, W.; Romas, N.A. Mol. Endocrinol. 1998, 12, 123–136.

[21] Gershagen, S.; Lundwall, A.; Fernlund, P. Nucl. Acids Res. 1989, 17, 9245–9258.

[22] Ghosh, R.C.; Chauhanhvs, R.S. Br. Vet. J. 1990, 146, 457–462.

[23] Oddo, M.; Calandra, T.; Bucala, R.; Meylan, P.R.A. Infect. Immun. 2005, 73, 3783–3786.

[24] Eaton, D.L.; Gallagher, E.P. Toxicology. 1994, 34, 135–172.

[25] Gallagher, E.P.; Kunze, K.L.; Stapleton, P.L.; Eaton, D.L. Toxicol. Appl. Pharmacol. 1996, 141, 595–606.

Exploration of the mechanisms of Aflatoxin B1 toxicity and the targets of Oltipraz by reverse docking

RichHTML

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 1

Recommended Articles

Metrics

Comments