Abstract
Five novel derivatives 1a, 1b, 1c, 2 and 3 of brevifoliol were synthesized. The structures of all the synthesized derivatives were established on the basis of IR, 1H NMR, 13C NMR and mass spectral data. All the five derivatives were tested for in vitro cytotoxicity against four human cancer cell lines. The result showed that compound 1a, 1b and 1c exhibited significant inhibition of cell growth. The mechanism of action of novel glucosidated derivatives have been explored by in silico molecular docking for anticancer activity against human lung, prostate and cervix cancer cell lines. Based on reported experimental activities on human cancer cell lines, specific molecular targets (e.g. microtubule in case of human lung cancer cell line A-549; indoleamine 2,3-dioxygenase in case of prostate cancer cell lines PC-3 and DU-145 and uridine phosphorylase 1 in case of Hela cell line) have been selected for docking studies and successfully validated for anticancer activity of brevifoliol derivatives.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Alushin GM, Ramey VH, Pasqualato S, Ball DA, Grigorieff N, Musacchio A, Nogales E (2010) The Ndc80 kinetochore complex forms oligomeric arrays along microtubules. Nature 467:805–810
Appendino G, Barboni L, Gariboldi P, Bombordelli E, Gabetta B, Viterbo D (1993) Revised structure of brevifoliol and some baccatin VI derivatives. J Chem Soc Chem Commun 33:1587–1589
Baloglu E, Kingston DGI (1999) The taxane diterpenoids. J Nat Prod 62:1448–1472
Balza F, Tachibana S, Barrios H, Towers GHN (1991) Brevifoliol, a taxane from Taxus brevifolia. Phytochemistry 30:1613–1614
Chattopadhyay SK, Tripathi S, Darokar MP, Faridi U, Sisodia B, Negi S, Kumar JK, Khanuja SPS (2008) Syntheses and cytotoxicities of the analogues of the taxoid brevifoliol. Eur J Med Chem 43:1499–1505
Georg GI, Gollapudi SR, Grunewald GL, Gunn CW, Himes RH, Rao BK, Liang XZ, Mirhom YW, Mitscher LA, Velde DGV, Ye QM (1993a) A reinvestigation of the taxol content of Himalayan Taxus wallichiana Zucc. and a revision of the structure of brevifoliol. Bioorg Med Chem Lett 3:1345–1348
Georg GI, Cheruvallath ZS, Velde DV, Ye QM, Mitscher LA, Himes RH (1993b) Semisynthesis and biological evaluation of brevifoliol 13-[N-benzoyl-(2′R,3′S)-3′-phenylisoserinate. Bioorg Med Chem Lett 3:1349–1350
Khanuja SPS, Kumar TRS, Garg A, Misra RK, Chattopadhyay SK, Srivastva S, Negi AS (2002) United States Patent Publication No. 20040127561 A1
Monks A, Scudiero D, Skehan P, Shoemaker R, Paull K, Vistica D, Hose C, Langley J, Cronise P, Vaigro-Wolff A, Gray-Goodrich M, Campbell H, Mayo J, Boyd M (1991) Feasibility of a high-flux anticancer drug screen using a diverse panel of cultured human tumor cell lines. J Natl Cancer Inst 83:757–766
Oberlies NH, Kroll DJ (2004) Camptothecin and taxol: historic achievements in natural products research. J Nat Prod 67:129–135
Ramalingam S, Belani CP (2004) Paclitaxel for non-small cell lung cancer. Expert Opin Pharmacother 5:1771–1780
Roosild TP, Castronovo S (2010) Active site conformational dynamics in human uridine phosphorylase 1. PLoS ONE 5:e12741
Schiff PB, Horwitz SB (1980) Taxol stabilizes microtubules in mouse fibroblast cells. Proc Natl Acad Sci USA 77:1561–1565
Schiff PB, Fant J, Horwitz SB (1979) Promotion of microtubule assembly in vitro by taxol. Nature 277:665–667
Shi QW, Zhao YM, Si XT, Li ZP, Yamada T, Kiyota H (2006) 1-Deoxypaclitaxel and abeo-taxoids from the seeds of Taxus mairei. J Nat Prod 69:280–283
Skehan P, Storeng R, Scudiero D, Monks A, Mohan JM, Vistica D, Warren JT, Bokesch H, Kenney S, Boyd MR (1990) New colorimetric cytotoxic assay for anticancer-drug screening. J Natl Cancer Inst 82:1107–1112
Sugimoto H, Oda S, Otsuki T, Hino T, Yoshida T, Shiro Y (2006) Crystal structure of human indoleamine 2,3-dioxygenase: catalytic mechanism of O2 incorporation by a heme-containing dioxygenase. Proc Natl Acad Sci USA 103:2611–2616
Tremblay S, Soucy C, Towers N, Gunning PJ, Breau L (2004) Characterization of an abeo-taxane: brevifoliol and derivatives. J Nat Prod 67:838–845
Trott O, Olson AJ (2010) AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization and multithreading. J Comp Chem 31:455–461
Wani MC, Taylor HL, Wall ME, Coggin P, McPhail AT (1971) Plant antitumor agents. VI. The isolation and structure of taxol, a novel antileukemic and antitumour agent from Taxus brevifolia. J Am Chem Soc 93:2325–2327
Zhao Y, Guo N, Lou LG, Cong YW, Peng LY, Zhao QS (2008) Synthesis, cytotoxic activity, and SAR analysis of the derivatives of taxchinin A and brevifoliol. Bioorg Med Chem 16:4860–4871
Acknowledgments
We are grateful to the director, CSIR-CIMAP, Lucknow for providing necessary facilities and financial assistance from the CSIR (Council of Scientific and Industrial Research) networking project NWP-09 is gratefully acknowledged.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Kaur, R., Chattopadhyay, S.K., Chatterjee, A. et al. Synthesis and in vitro anticancer activity of brevifoliol derivatives substantiated by in silico approach. Med Chem Res 23, 4138–4148 (2014). https://doi.org/10.1007/s00044-014-0980-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00044-014-0980-6