Computational drug designing of fungal pigments as potential aromatase inhibitors

Authors

  • Nighat Fatima Department of Pharmacy, COMSATS Institute of Information Technology Abbottabad Pakistan.
  • Abida Kalsoom
  • Amara Mumtaz
  • Syed Aun Muhammad

DOI:

https://doi.org/10.3329/bjp.v9i4.20435

Keywords:

Ankaflavin, Aromatase, Breast cancer, Monascin

Abstract

The existing aromatase inhibitors produced unwelcome effects impose the discovery of novel drugs with privileged selectivity, a reduced amount of toxicity and humanizing potency. In this study, we illuminate the binding mode of polyketide azaphilanoid pigments monascin, ankaflavin, monascorubrin and monascorubramine isolated from Monascus fungus to the aromatase by molecular docking. The 3-dimensional structure of aromatase enzyme (PDB: 4KQ8) was obtained from the Protein Data Bank. PatchDock docking software was used to analyze structural complexes of the aromatase with monascus pigments. Comparatively, the AutoGrid model presented the most briskly constructive binding mode of monascin to aromatase. Docked energies in kcal/mol are: monascin;-13.2; monascorubramine:-12.8, monascorubrin:-12.3; ankaflavin: -10.5. These outcomes exposed these ligands could be potential drugs to treat hormone dependent breast cancer.

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References

Akihisa T, Tokuda H, Ukiya M, Kiyota A, Yasukawa K, Sakamoto N, Kimura Y, Suzuki T, Takayasu J, Nishino H. Anti-tumor-initiating effects of monascin, an azaphilonoid pigment from the extract of Monascus pilosus fermented (red-mold rice). Chem Biodivers. 2005; 2: 1305-07.

Chomcheon P, Wiyakrutta S, Sriubolmas N, Ngamrojana-vanich N, Kengtong S, Mahidol C, Ruchirawat S, Kittakoop P. Aromatase inhibitory, radical scavenging, and antioxidant activities of depsidones and diaryl ethers from the endophytic fungus Corynespora cassiicola L36. Phytochemistry 2009; 70: 407-13.

Huang B. MetaPocket: A meta approach to improve protein ligand binding site prediction, OMICS. 2009; 13: 325-30.

Jongen VHWM, Thijssen JHH, Hollema H, Donker GH, Santema JG, Van der zee AGJ, Heineman MJ. Is aromatase cytochrome P450 involved in the pathogenesis of endometrioid endometrial cancer? Int J Gynecol Cancer. 2005; 15: 529-36.

Lee BH, Hsu WH, Chang YY, Kuo HF, Hsu YW, Pan TM. Ankaflavin: A natural novel PPARγ agonist up-regulates Nrf2 to attenuate methylglyoxal-induced diabetes in vivo. Free Radic Biol Med. 2012; 53: 2008-16.

Lee CL, Wang JJ, Kuo SL, Pan TM. Monascus fermentation of dioscorea for increasing the production of cholesterol-lowering agent-moacolin K and antiinlammation agent-monascin. Appl. Microbiol Biotecehnol. 2006; 72: 1254-62.

Maiti A, Cuendet M, Croy VL, Endringer DC, Pezzuto JM, Cushman M. Synthesis and biological evaluation of (+/-)-abyssinone II and its analogues as aromatase inhibitors for chemoprevention of breast cancer. J Med Chem. 2007; 50: 2799-806.

Mapari SA, Thrane U, Meyer AS. Fungal polyketide azaphilone pigments as future natural food colorants? Trends in Biotechnol. 2010; 28: 300-07.

Muhammad SA, Ali A, Ismail T, Zafar R, Ilyas U, Ahmad J. In silico study of anti-carcinogenic lysyl oxidase-like 2 inhibitors. Com Biol Chem. 2014; 51: 71-82.

Pyrkov TV, Chugunov AO, Krylov NA, Nolde DE, Efremov RG. PLAT-INUM: A web tool for analysis of hydrophobic/hydrophilic organization of biomolecular complexes. Bioinformatics. 2009; 25: 1201-02.

Schneidman-Duhovny D, Inbar Y, Nussinov R, Wolfson HJ. PatchDock and SymmDock: Servers for rigid and symmetric docking. Nucl Acids Res. 2005; 33: W363-67.

Sotiriou C, Pusztai L. Gene-expression signatures in breast cancer. N Engl J Med. 2009; 360: 790-800.

Sotiriou C, Wirapati P, Loi S, Harris A, Fox S, Smeds J, Nordgren H, Farmer P, Praz V, Haibe-Kains B, Desmedt C, Larsimont D, Cardoso F, Peterse H, Nuyten D, Buyse M, Van de Vijver MJ, Bergh J, Piccart M, Delorenzi M. Gene expression profiling in breast cancer: Understanding the molecular basis of histologic grade to improve prognosis. J Natl Cancer Inst. 2006; 98: 262-72.

Standish LJ, Sweet ES, Novack J, Wenner CA, Bridge C, Nelson A, Martzen M, Torkelson C. Breast cancer and the immune system. J Soc Integr Oncol. 2008; 6: 158-68.

Sureram S, Wiyakrutta S, Ngamrojanavanich N, Mahidol C, Ruchirawat S, Kittakoop P. Depsidones, aromatase inhibitors and radical scavenging agents from the marine-derived fungus Aspergillus unguis CRI282-03. Planta Med. 2012; 78: 582-88.

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Published

2014-11-07

How to Cite

Fatima, N., A. Kalsoom, A. Mumtaz, and S. A. Muhammad. “Computational Drug Designing of Fungal Pigments As Potential Aromatase Inhibitors”. Bangladesh Journal of Pharmacology, vol. 9, no. 4, Nov. 2014, pp. 575-9, doi:10.3329/bjp.v9i4.20435.

Issue

Vol. 9 No. 4 (2014)

Section

Research Articles

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