• Paranjeet Kaur Lovely Professional University, Jalandhar-Delhi G.T. Road (NH-1), Phagwara, Punjab (INDIA)



Antiandrogen, Oxadiazole, Triazole, Autodock Vina, Molecular docking, Prostate cancer


Objective: To identify the novel and simple bioactive antiandrogens, that can overcome to side effects as well as drug resistance.

Methods: The AutoDock Vina (ADT) 1.5.6 software is used for molecular docking purposes. The molecular structures were drawn in ChemBiodraw ultra and by the help of ChemBiodraw 3D, all structures were energy minimized by MM2 method and converted to pdb extension file which is readable at the ADT interface.

Results: Total ten compounds from both series were shown better binding affinity than R-bicalutamide including oxadiazole and triazole series. Among these pk42 and pk46 were studied in-depth which showed best binding affinity to the androgen receptor. The cis-isomers were found better than their trans-isomer.

Conclusion: Novel 5-styryl-1,2,4-oxadiazole/triazole derivatives were studied through molecular modeling using Autodock Vina. The potent compounds which showed better binding affinity than R-bicalutamide like pk24 and 46 were further analyzed for their interactions. The conformational effect also found significant in binding to the androgen receptor.


Download data is not yet available.


Jemal A, Thomas A, Murray T, Thun M. Cancer statistics. CA Cancer J Clin 2002;52:23.

Eden T. Aetiology of childhood leukaemia. Cancer Treat Rev 2014;36:286-97.

American Cancer Society. Cancer Facts and fig. 2014. Atlanta: American Cancer Society; 2014.

Jain S, Saxena S, Kumar A. Epidemiology of prostate cancer in India. Meta Gene 2014;2:596–605.

Brawer MK. Testosterone replacement in men with andropause: an overview. Rev Urol 2004;6:S9–S15.

Heinlein CA, Chang C. Androgen receptor in prostate cancer. Endocr Rev 2004;25:276–308.

Shang Y, Myers M, Brown M. Formation of the androgen receptor transcription complex. Mol Cell 2002;9:601–10.

Wang Q, Carroll JS, Brown M. Spatial and temporal recruitment of androgen receptor and its coactivators involve chromosomal looping and polymerase tracking. Mol Cell 2005;19:631–42.

Burger A. Abraham DJ. Burger’s medicinal chemistry and drug discovery. 6th ed. Wiley: Hoboken(NJ); 2003.

Foye WO, Williams DA, Lemke TL. Foye’s principles of medicinal chemistry. 5th ed. Lippincott Williams and Wilkins: Philadelphia (PA); 2002.

Singh SM, Gauthier S, Labrie F. Androgen receptor antagonists (antiandrogens): structure-activity relationships. Curr Med Chem 2000;7:211-47.

Goodman LS, Hardman JG, Limbird LE, Gilman AG. Goodman and Gilman’s the pharmacological basis of therapeutics. 10th ed. McGraw-Hill Medical Pub. Division (NY); 2001.

Huggins C, Stevens R, Hodges CV. The effect of castration on advanced carcinoma of the prostate gland. Arch Surg 1947;43:209-23.

Westin P, Stattin P, Damber JE, Bergh A. Castration therapy rapidly induces apoptosis in a minority and decreases cell proliferation in a majority of human prostatic tumors. Am J Pathol 1995;146:1368-75.

Oettel M. Testosterone metabolism, dose-response relationships and receptor polymorphisms: selected pharmacological/ toxicological considerations on benefits versus risks of testosterone therapy in men. Aging Male 2003;6:230-56.

Migeon BR, Brown TR, Axelman J, Migeon CJ. Studies of the locus for androgen receptor: localization on the human X chromosome and evidence for homology with the Tfm locus in the mouse. Proc Natl Acad Sci USA 1981;78:6339-43.

Lubahn DB, Joseph DR, Sullivan PM, Willard HF, French FS, Wilson EM. Cloning of human androgen receptor complementary DNA and localization to the X chromosome. Science 1988;240:327-30.

Chang CS, Kokontis J, Liao ST. Structural analysis of complementary DNA and amino acid sequences of human and rat androgen receptors. Proc Natl Acad Sci USA 1988;85:7211-5.

Lubahn DB, Joseph DR, Sar M, Tan J, Higgs HN, Larson RE, et al. The human androgen receptor: complementary deoxyribonucleic acid cloning, sequence analysis and gene expression in prostate. Mol Endocrinol 1988;2:1265-75.

Trapman J, Klaassen P, Kuiper GG, van der Korput JA, Faber PW, van Rooij HC, et al. Cloning, structure and expression of a cDNA encoding the human androgen receptor. Biochem Biophys Res Commun 1988;153:241-8.

McEwan I. Molecular mechanisms of androgen receptor-mediated gene regulation: structure-function analysis of the AF-1 domain. J Endocr Relat Cancer 2004;11:281-93.

Chawnshang C. Androgens and androgen receptor: mechanisms functions, and clinical applications. Kluwer Academic Publishers: Boston (MA); 2002.

Bohl CE, Gao W, Miller DD, Bell CE, Dalton JT. Structural basis for antagonism and resistance of bicalutamide in prostate cancer. Proc Natl Acad Sci 2005;102:6201-5.

Marhefka CA, Moore BM, Bishop TC, Kirkovsky L, Mukherjee A, Dalton JT, et al. Homology modeling using multiple molecular dynamics simulations and docking studies of the human androgen receptor ligand-binding domain bound to testosterone and nonsteroidal ligands. J Med Chem 2001;44:1729-40.

Zhou ZX, Wong CI, Sar M, Wilson EM. The androgen receptor: an overview. Recent Prog Horm Res 1994;49:249-74.

Myers EW, Miller W. Approximate matching of regular expressions. Bull Math Biol 1989;51:5-37.

Pratt WB, Toft DO. Steroid receptor interactions with heat shock protein and immunophilin chaperones. Endocr Rev 1997;18:306-60.

Heinlein CA, Chang C. Androgen receptor (AR) coregulators: an overview. Endocr Rev 2002;23:175-200.

Shang Y, Myers M, Brown M. Formation of the androgen receptor transcription complex. Mol Cell 2002;9:601-10.

Matias PM, Donner P, Coelho R, Thomaz M, Peixoto C, Macedo S, et al. Structural evidence for ligand specificity in the binding domain of the human androgen receptor. Implications for pathogenic gene mutations. J Biol Chem 2000;275:26164-71.

He B, Minges JT, Lee LW, Wilson EM. The FXXLF motif mediates androgen receptor-specific interactions with coregulators. J Biol Chem 2002;277:10226-35.

Wurtz JM, Bourguet W, Renaud JP, Vivat V, Chambon P, Moras D, et al. A canonical structure for the ligand-binding domain of nuclear receptors. Nat Struct Biol 1996;3:87-94.

Brzozowski AM, Pike AC, Dauter Z, Hubbard RE, Bonn T, Engstrom O, et al. Molecular basis of agonism and antagonism in the estrogen receptor. Nature 1997;389:753-8.

Heery DM, Kalkhoven E, Hoare S, Parker MG. A signature motif in transcriptional co-activators mediates binding to nuclear receptors. Nature 1997;387:733-6.

Bourguet W, Germain P, Gronemeyer H. Nuclear receptor ligand-binding domains: three-dimensional structures, molecular interactions, and pharmacological implications. Trends Pharmacol Sci 2000;21:381-8.

Hur E, Pfaff SJ, Payne ES, Gron H, Buehrer BM, Fletterick RJ. Recognition and accommodation at the androgen receptor coactivator binding interface. J PLoS Biol 2004;2:E274.

Sathya G, Chang CY, Kazmin D, Cook CE, McDonnell DP. Pharmacological uncoupling of androgen receptor-mediated prostate cancer cell proliferation and prostate-specific antigen secretion. Cancer Res 2003;63:8029-36.

He B, Gampe RT, Jr Kole AJ, Hnat AT, Stanley TB, An G, et al. Structural basis for androgen receptor interdomain and coactivator interactions suggests a transition in nuclear receptor activation function dominance. Mol Cell 2004;16:425-38.

Warnmark A, Treuter E, Gustafsson JA, Hubbard RE, Brzozowski AM, Pike AC. Interaction of transcriptional intermediary factor 2 nuclear receptor box peptides with the coactivator binding site of estrogen receptor alpha. J Biol Chem 2002;277:21862-8.

Chang CY, McDonnell DP. Androgen receptor-cofactor interactions as targets for new drug discovery. Trends Pharmacol Sci 2005;26:225-8.

Langley E, Kemppainen JA, Wilson EM. Evidence for anti-parallel orientation of the ligand-activated human androgen receptor dimer. J Biol Chem 1995;270:29983-90.

Khatik GL, Kaur J, Kumar V, Tikoo K, Venugopalan P, Nair VA. Aldol derivatives of Thioxoimidazolidinones as potential anti-prostate cancer agents. Eur J Med Chem 2011;46:3291-301.

Khatik GL, Kaur J, Kumar V, Tikoo K, Nair VA. 1,2,4-Oxadiazoles: a new class of anti-prostate cancer agents. Bioorg Med Chem Lett 2012;22:1912-6.

Kumar V, Rachamalla M, Nandekar P, Khatik GL, Sangamwar AT, Tikoo K, et al. Design and synthesis of optically pure 3-Aryl-6-methyl-2-thioxotetrahydropyrimidin-4(1H)-ones as anti-prostate cancer agents. RSC Adv 2014;4:37868-77.

Kaur P, Khatik GL. Advancements in non-steroidal antiandrogens as potential therapeutic agents for the treatment of prostate cancer. Mini Rev Med Chem 2016;16:531-46.

Chaurasiya S, Kaur P, Nayak SK, Khatik GL. Virtual screening for identification of novel potent EGFR inhibitors through Autodock Vina molecular modeling software. J Chem Pharm Res 2016;8:353-60.

Shruthy VS, Shakkeela Y. In silico design, docking, synthesis and evaluation of thiazole Schiff bases. Int J Pharm Pharm Sci 2014;6:271-5.

Muthukala B, Kanakarajan S, Kamalanathan A. In silico docking of Quercetin compound against the Hela cell line proteins. Int J Curr Pharm Res 2015;7:13-6.

Munusami P, Vasavi C, Divya G. Molecular docking studies on flavonoid compounds: an insight into aromatase inhibitors. Int J Pharm Pharm Sci 2014;6:141-8.

Kalita JM, Ghosh SK, Sahu S, Dutta M. A statistical analysis to find out an appropriate docking method. Asian J Pharm Clin Res 2015;7:158-60.

Trott O, Olson AJ. AutoDock vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem 2010;31:455-61.

Energy minimizations were performed MM2 Interface program on ChemBio3D Ultra 12.0, and structures were drawn by ChemBioDrwa Ultra 12.0 (Cambridge Soft); 1985.



How to Cite

Kaur, P., and G. L. Khatik. “IDENTIFICATION OF NOVEL 5-STYRYL-1,2,4-OXADIAZOLE/TRIAZOLE DERIVATIVES AS THE POTENTIAL ANTI-ANDROGENS THROUGH MOLECULAR DOCKING STUDY”. International Journal of Pharmacy and Pharmaceutical Sciences, vol. 8, no. 10, Oct. 2016, pp. 72-77, doi:10.22159/ijpps.2016v8i10.13844.



Original Article(s)