Abstract
A novel method for the partial synthesis of the rare triterpenoid, 3-epihydroxy lup-20(29)-en-19(28)-olide, and 1 from betulinic acid is reported. The binding efficiency, mode of binding for different compounds to the central catalytic domain of topoisomerase IIα, was calculated from a complete 3D molecular docking study on the crystal structure of the enzyme (1bgw, pdb). The compounds 1, 2b, and 2d showed a dose-dependent inhibition of catalytic activity of topoisomerase IIα.
Similar content being viewed by others
References
Berger JM, Gamblin SJ, Harrison SC, Wang JC (1996) Structure and mechanism of DNA topoisomerase II. Nature 379:225–233
Camp D, Davis RA, Campitelli M, Ebdon J, Quinn RJ (2012) Cytotoxic Diterpenoids from Sapium insigne. J Nat Prod 75:722–724
Deweese JE, Osheroff N (2009) The DNA cleavage reaction of topoisomerase II: wolf in sheep’s clothing. Nucleic Acid Res 37:738–748
Dexheimer TS, Pommier Y (2008) DNA cleavage assay for the identification of topoisomerase I inhibitors. Nat Protoc 3:1736–1750
Dong KC, Berger JM (2007) Structural basis for gate-DNA recognition and bending by type IIA topoisomerases. Nature 450:1201–1205
Frisch MJ et al (2009) Gaussian 09, Revision A.02, Gaussian, Inc., Wallingford CT
Ganguly A, Das B, Roy A, Sen N, Dasgupta SB, Mukhopadhyay S, Majumder HK (2007) Betulinic acid, a catalytic inhibitor of topoisomerase I, inhibits reactive oxygen species-mediated apoptotic topoisomerase I-DNA cleavable complex formation in prostate cancer cells but does not affect the process of cell D. Cancer Res 67:11850–11856
Ghosh P, Mandal A, Ghosh J, Pal C, Nanda AK (2012) Synthesis of bioactive 28-hydroxy-3-oxolup-20(29)-en-30-al with antileukemic activity. J Asian Nat Prod Res 14:141–149
Harvey A (2008) Natural products in drug discovery. Drug Discov Today 13:894–901
Mandal A, Ghosh S, Bothra AK, Nanda AK, Ghosh P (2012) Synthesis of friedelan triterpenoid analogs with DNA topoisomerase IIα inhibitory activity and their molecular docking studies. Eur J Med Chem 54:137–143
Noble CG, Maxwell A (2002) The role of GyrB in the DNA cleavage-religation reaction of DNA gyrase: a proposed two metal-ion mechanism. J Mol Biol 318:361–371
Symon AV, Caplun AP, Vlasenkova NK, Gerasimova GK, Shon LB, Litvin EF, Kozlova LM, Surkova EL, Shvets VI (2003) Epimerization of hydroxyl group in lupan series triterpenoids. Russ J Bioorg Chem 29:185–189
Syrovets T, Buchele B, Gedig E, Slupsky JR, Simmet T (2000) Acetyl-boswellic acids are novel catalytic inhibitors of human topoisomerases I and IIα. Mol Pharmacol 58:71–81
Vosberg HP (1985) DNA topoisomerases: enzymes that control DNA conformation. C. Curr Top Microbiol Immunol 114:19–102
Wess G, Urmann M, Sickenberger B (2001) Medicinal chemistry of chalcogens. Angew Chem Int Ed 40:3341–3350
Williams PG (2009) Panning for chemical gold: marine bacteria as a source of new therapeutics. Trends Biotechnol 27(45–52):8
Wu CC, Li TK, Farh L, Lin LY, Lin TS, Yu YJ, Yen TJ, Chiang CW, Chan NL (2011) Structural basis of type II topoisomerase inhibition by the anticancer drug etoposide. Science 22:459–452
Acknowledgments
Financial support from UGC, New Delhi, India, was cordially acknowledged to carry out the work.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Mandal, A., Ghosh, A., Ghosh, S. et al. 3-Epihydroxy lup-20(29)-en-19(28)-olide: partial synthesis, antitopoisomerase activity, and 3D molecular docking. Med Chem Res 25, 1087–1095 (2016). https://doi.org/10.1007/s00044-016-1551-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00044-016-1551-9