Interaction of marine Streptomyces compounds with selected cancer drug target proteins by in silico molecular docking studies



The criteria currently followed for selecting antitumor compounds include agents that can target apoptosis inhibitor proteins and cancer cell markers. In silico studies are often used to identify suitable antitumor compounds for the cancer targets. The aim of the present study is to evaluate the interactions of some antitumor compounds reported from marine Streptomyces with cancer target proteins. Nine compounds were selected from marine Streptomyces based on previous reports and evaluated for their interactions with cancer target proteins by in silico molecular docking approach. Interactions of the selected ligand with target proteins were studied by PatchDock bioinformatics docking tool. Among the compounds tested marmycin A was interacted very effectively with human epidermal growth factor receptor 2 (HER2) and showed a least binding energy of −472.92 kcal/mol. The compound altemicidin showed a least binding energy of −415.66 kcal/mol with cyclin dependent kinase 4 (CDK4). The ligands resistoflavine and resistomycin also interacted with HER2 and showed the binding energy of −402.10 kcal/mol and −377.78 kcal/mol respectively. Other ligands proximycin A, chandrananimycin C, echinosporin, streptochlorin and streptokordin also showed the binding energy of −341.11 kcal/mol, −313.31 kcal/mol, −305.64 kcal/mol, −291.91 kcal/mol and 222.34 kcal/mol respectively with CDK4 protein. These results of our study suggest that HER2 and CDK4 are better cancer drug targets for therapy.

Key words

in silico molecular docking PatchDock marine Streptomyces marmycin A altemicidin human epidermal growth factor receptor 2 cyclin dependent kinase 4 


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  1. [1]
    António, M.R.S., Schulze-Makuchv, D. 2009. The immune system as key to cancer treatment: Triggering its activity with microbial agents. Biosci Hypotheses 2, 388–392.CrossRefGoogle Scholar
  2. [2]
    Boopathy, S.N., Kathiresan, K. 2010. Anticancer drugs from marine flora: An overview. J Oncol 2010, 214186.Google Scholar
  3. [3]
    Cui, C.B., Liu, H.B., Gu, J.Y., Gu, Q.Q., Cai, B., Zhang, D.Y., Zhu, T.J. 2007. Echinosporins as new cell cycle inhibitors and apoptosis inducers from marine-derived Streptomyces albogriseolus. Fitoterapia 78, 238–240.PubMedCrossRefGoogle Scholar
  4. [4]
    Dharmaraj, S. 2010. Marine Streptomyces as a novel source of bioactive substances. World J Microbiol Biotechnol 26, 2123–2139.CrossRefGoogle Scholar
  5. [5]
    Fiedler, H.P., Bruntner, C., Riedlinger, J., Bull, A.T., Knutsen, G., Goodfellow, M., Jones, A., Maldonado, L., Pathom-aree, W., Beil, W., Schneider, K., Keller, S., Sussmuth, R.D. 2008. Proximicin A, B and C, novel aminofuran antibiotic and anticancer compounds isolated from marine strains of the actinomycete Verrucosispora. J Antibiot 61, 158–163.PubMedCrossRefGoogle Scholar
  6. [6]
    Gorajana, A., Kurada, B.V., Peela, S., Jangam, P., Vinjamuri, S., Poluri, E., Zeeck, A. 2005. 1-Hydroxy-1-norresistomycin, a new cytotoxic compound from a marine actinomycete, Streptomyces chibaensis AUBN1/7. J Antibiot 58, 526–529.PubMedCrossRefGoogle Scholar
  7. [7]
    Hanahan, D., Weinberg, R.A. 2000. The role of apoptosis in cancer development and treatment response. Cell 100, 57–70.PubMedCrossRefGoogle Scholar
  8. [8]
    Hanson, B.E., Vesole, D.H. 2009. Retaspimycin hydrochloride (IPI-504): A novel heat shock protein inhibitor as an anticancer agent. Expert Opin Investig Drugs 18, 1375–1383.PubMedCrossRefGoogle Scholar
  9. [9]
    Hirai, H., Kawanishi, N., Iwasawa, Y. 2005 Recent advances in the development of selective small molecule inhibitors for cyclin-dependent kinases. Curr Top Med Chem 5,167–179.PubMedCrossRefGoogle Scholar
  10. [10]
    Innis, C.A. 2007. siteFiNDERj3D: A web-based tool for predicting the location of functional sites in proteins. Nucl Acids Res 35, W489–W494.PubMedCrossRefGoogle Scholar
  11. [11]
    Jakobi, K., Hertweck, C. 2004. A gene cluster encoding resistomycin biosynthesis in Streptomyces resistomycificus: Exploring polyketide cyclization beyond linear and angucyclic patterns. J Am Chem Soc 126, 2298–2299.PubMedCrossRefGoogle Scholar
  12. [12]
    Jemal, A., Siegel, R., Xu, J., Ward, E. 2010. Cancer Statistics, 2010. CA: Cancer J Clinicians 60, 277–300.CrossRefGoogle Scholar
  13. [13]
    Jeong, S.Y., Shin, H.J., Kim, T.S., Lee, H.S., Park, S.K., Kim, H.M. 2006. Streptokordin, a new cytotoxic compound of the methylpyridine class from a marinederived Streptomyces sp. KORDI-3238. J Antibiot 59, 234–240.PubMedCrossRefGoogle Scholar
  14. [14]
    Jha, D.K., Panda, L., Anbarasu, A. 2011. Comparative analysis and identification of novel β-lactamase inhibitors. J Pharma Biosci 2, B88–B98.Google Scholar
  15. [15]
    Lansiaux, A., Pourquier, P. 2011. Molecular determinants of response to topoisomerase II inhibitors. Cancer 98, 1299–1310.Google Scholar
  16. [16]
    Lee, C.H., Huntsman, D.G., Cheang, M.C., Parker, R.L., Brown, L., Hoskins, P., Miller, D., Gilks, C.B. 2005. Assessment of Her-1, Her-2, And Her-3 expression and Her-2 amplification in advanced stage ovarian carcinoma. Int J Gynecol Pathol 24, 147–152.PubMedCrossRefGoogle Scholar
  17. [17]
    Liu, F., Liu, Q., Yang, D., Bollag, W.B., Robertson, K., Wu, P., Liu, K. 2011.Verticillin overcomes apoptosis resistance in human colon carcinoma through DNA methylation-dependent upregulation of BNIP3. Cancer Res 71, 6807–6816.PubMedCrossRefGoogle Scholar
  18. [18]
    Martin, G.D., Tan, L.T., Jensen, P.R., Dimayuga, R.E., Fairchild, C.R., Raventos-Suarez, C., Fenical, W. 2007. Marmycins A and B, cytotoxic pentacyclic C-glycosides from a marine sediment-derived actinomycete related to the genus Streptomyces. J Nat Prod 70, 1406–1409.PubMedCrossRefGoogle Scholar
  19. [19]
    Maskey, R.P., Li, F., Qin, S., Fiebig, H.H., Laatsch, H. 2003. Chandrananimycins A-C: Production of novel anticancer antibiotics from a marine Actinomadura sp. isolate M048 by variation of medium composition and growth conditions. J Antibiot 56, 622–629.PubMedCrossRefGoogle Scholar
  20. [20]
    Messaoudi, S., Peyrat, J.F., Brion, J.D., Alami, M. 2008. Recent advances in Hsp90 inhibitors as antitumor agents. Anticancer Agents Med Chem 8, 761–782.PubMedCrossRefGoogle Scholar
  21. [21]
    Miyata, Y. 2005. Hsp90 inhibitor geldanamycin and its derivatives as novel cancer chemotherapeutic agents. Curr Pharm Des 11, 1131–1138.PubMedCrossRefGoogle Scholar
  22. [22]
    Moasser, M.M. 2007. The oncogene HER2: Its signaling and transforming functions and its role in human cancer pathogenesis. Oncogene 26, 6469–6487.PubMedCrossRefGoogle Scholar
  23. [23]
    Murakami, M. 2012. Signaling required for blood vessel maintenance: Molecular basis and pathological manifestations. Int J Vasc Med 2012, 293641.PubMedGoogle Scholar
  24. [24]
    Olano, C., Méndez, C., Salas J.A. 2009. Antitumor compounds from marine actinomycetes. Marine Drugs 7, 210–248.PubMedCrossRefGoogle Scholar
  25. [25]
    Ortega, S., Malumbres, M., Barbacid, M. 2002. Cyclin D-dependent kinases, INK4 inhibitors and cancer. Biochim Biophys Acta 1602, 73–87.PubMedGoogle Scholar
  26. [26]
    Pripp, A.H. 2007. Docking and virtual screening of ACE inhibitory dipeptides. Eur Food Res Technol 225, 589–592.CrossRefGoogle Scholar
  27. [27]
    Rutledge, S.E., Chin, J.W., Schepartz, A. 2002. A view to a kill: Ligands for Bcl-2 family proteins. Curr Opin Chem Biol 6, 479–485.PubMedCrossRefGoogle Scholar
  28. [28]
    Shah, M.A. Schwartz, G.K. 2006. Cyclin dependent kinases as targets for cancer therapy. Cancer Ther 1, 311–332.Google Scholar
  29. [29]
    Shin, H.J., Jeong, H.S., Lee, H.S., Park, S.K., Kim, H.M., Kwon, H.J. 2007. Isolation and structure determination of streptochlorin, an antiproliferative agent from a marine-derived Streptomyces sp. 04DH110. J Microbiol Biotechnol 17, 1403–1406.PubMedGoogle Scholar
  30. [30]
    Takahashi, A., Kurasawa, S., Ikeda, D., Okami, Y., Takeuchi, T. 1989. Altemicidin, a new acaricidal and antitumor substance. I. Taxonomy, fermentation, isolation and physico-chemical and biological properties. J Antibiot (Tokyo) 42, 1556–1561.CrossRefGoogle Scholar

Copyright information

© International Association of Scientists in the Interdisciplinary Areas and Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.School of Biosciences and TechnologyVIT UniversityVelloreIndia

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