Ramanathan K, Shanthi V, Kanika Verma


Objective: Paclitaxel is one of the most effective anticancer agents. It is used as a chemotherapy agent for a spectrum of cancer types. However,
paclitaxel resistance is one of the foremost problems for chemotherapy. Most importantly, an emergence of paclitaxel resistance due to mutation
(F270V) in β-tubulin has been extremely deliberated in recent years. With the rise of paclitaxel-resistant mutation in β-tubulin, there is a need to add
a novel inhibitor from natural source, as they have less chance of getting resistance additionally less side effects. Keeping this in mind, we have utilized
experimental and in silico approaches to isolate the potent inhibitor for β-tubulin target protein.

Methods: We have extracted phytocompounds from Cassia fistula plant, and the structures were recognized with the help of gas chromatographymass
spectrometry technique. Subsequently, oral bioavailability and toxicity analysis were executed for the extracted compounds by employing
MOLINSPIRATION and OSIRIS program, respectively. Furthermore, docking analysis was performed using YASARA algorithm. In addition, bioactivity
analysis for the screened compounds was performed using prediction of activity spectra for substances program.

Results: The results from our analysis clearly depict that HOP-22(29)-EN-3.BETA.-OL could be a promising inhibitor for the treatment of cancer and
provide direction for future research. Further in vitro and in vivo exploration is also required to identify whether HOP-22(29)-EN-3.BETA.-OL have
anticancer effect or not.

Conclusion: The combination of computational approach and experimentalanalysis provides an easy approach to identify novel candidate for the target protein β-tubulin.

Keywords: Phytochemicals, Gas chromatography mass spectrometry, Bioavailability, Molecular docking, Prediction of activity spectra for substances

| PDF |


Mollinedo F, Gajate C. Microtubules, microtubule-interfering agents and apoptosis. Apoptosis 2003;8(5):413-50.

Zhou J, Giannakakou P. Targeting microtubules for cancer chemotherapy. Curr Med Chem Anticancer Agents 2005;5(1):65-71.

Jordan A, Hadfield JA, Lawrence NJ, McGown AT. Tubulin as a target for anticancer drugs: Agents which interact with the mitotic spindle. Med Res Rev 1998;18(4):259-96.

Dumontet C, Sikic BI. Mechanisms of action of and resistance to antitubulin agents: Microtubule dynamics, drug transport, and cell death. J Clin Oncol 1999;17(3):1061-70.

Newman DJ, Cragg GM, Snader KM. Natural products as sources of new drugs over the period 1981-2002. J Nat Prod 2003;66(7):1022-37.

Cragg GM, Newman DJ. Plants as a source of anti-cancer agents. J Ethnopharmacol 2005;100(1-2):72-9.

Anusha K, Govindappa M, Channabasava R, Chandrappa CP, Ramachandra YL, Prasad SK. Phytochemical analysis of Cassia fistula and its in vitro antimicrobial, antioxidant and anti-inflammatory activities. AMPR 2015;3(1):8-17.

Anusha K, Govindappa M, Ramachandra YL, Prasad SK. GC-MS analysis of methanol extract of cassia fistula and its in vitro anticancer activity on human prostate cancer cell line. IAJPS 2015;5(2):937-44.

Theeshan B, Vidushi SN, Okezie IA. Phytochemical constituents of cassia fistula. Afr J Biotechnol 2005;4(13):1530-40.

Kalaiselvan A, Gokulakrishnan K, Anand T. Gas chromatography-Mass spectrum analysis of bioactive components of the ethanol extract of Andrographis paniculata. J Pharm Biomed Sci 2012;20(20):1-3.

Ambritha B, Rekha R, Shanthia S, Monisha T, Lavanya R, Ramanathan K, et al. Investigation of Phytocompounds and Computational Approach for the Evaluation of Therapeutic Properties of Ethanolic Leaf Extract of Callistemon citrinus. Int J Pharm Sci Rev Res 2016;37(1):110-6.

Feng QL, Wu J, Chen GQ, Cui FZ, Kim TN, Kim JO. A mechanistic study of the antibacterial effect of silver ions on Escherichia coli and Staphylococcus aureus. J Biomed Mater Res 2000;52(4):662-8.

Ravichandran V, Tiah ZX, Subashini G, Terence FW, Eddy FC, Nelson J, et al. Biosynthesis of silver nanoparticles using mangosteen leaf extract and evaluation of their antimicrobial activities. J Saudi Chem Soc 2011;15:113-20.

Sermakkani M, Thangapandian V. GC-MS Analysis of cassia italic leaf methanol extract. Asian J Pharm Clin Res 2012;5(2):90-4.

Devi KV, Shanmugasundaram R, Mohan VR. GC-MS Analysis of ethanol extract of Entadapursaetha DC seed. Biosci Discov 2012;3(1):30-3.

Elavarasi S, Saravanan K, Renuka C. A systematic review on medicinal plants used to treat diabetes mellitus. IJPCBS 2013;3(3):983-92.

Subashri B, Justin Koil Pillai Y. A comparative study of antioxidant activity of Baccopa monnieri (L.) pennell using various solvent extracts and its GC-MS Analysis. Int J Pharm Pharm Sci 2014;6(2):494-8.

Xu S, Chi S, Jin Y, Shi Q, Ge M, Wang S, et al. Molecular dynamics simulation and density functional theory studies on the active pocket for the binding of paclitaxel to tubulin. J Mol Model 2012;18(1):377-91.

Guex N, Peitsch MC. SWISS-MODEL and the Swiss-PdbViewer: An environment for comparative protein modeling. Electrophoresis 1997;18(15):2714-23.

Feldman HJ, Snyder KA, Ticoll A, Pintilie G, Hogue CW. A complete small molecule dataset from the protein data bank. FEBS Lett 2006;580(6):1649-53.

Gasteiger J, Rudolph C, Sadowski J. Automatic generation of 3D-atomic coordinates for organic molecules. Tetrahedron Comput Methodol 1990;3:537-47.

Ertl P, Rohde B, Selzer P. Fast calculation of molecular polar surface area as a sum of fragment-based contributions and its application to the prediction of drug transport properties. J Med Chem 2000;43(20):3714-7.

Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev 1997;23:3-25.

Muegge I. Selection criteria for drug-like compounds. Med Res Rev 2003;23(3):302-21.

Buntrock RE. ChemOffice Ultra 7.0. J Chem Inf Comput Sci 2002;42(6):1505-6.

Sander T. OSIRIS Property Explorer. Allschwil: Actelion Pharmaceuticals Ltd.; 2001.

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(2):455-61.

Krieger E, Vriend G. Models@Home: Distributed computing in bioinformatics using a screensaver based approach. Bioinformatics 2002;18(2):315-8.

Li GH, Huang JF. CDRUG: A web server for predicting anticancer activity of chemical compounds. Bioinformatics 2012;28(24):3334-5.

Li GH, Huang JF. Inferring therapeutic targets from heterogeneous data: HKDC1 is a novel potential therapeutic target for cancer. Bioinformatics 2014;30(6):748-52.

Khurana N, Ishar MP, Gajbhiye A, Goel RK. PASS assisted prediction and pharmacological evaluation of novel nicotinic analogs for nootropic activity in mice. Eur J Pharmacol 2011;662(1-3):22-30.

Goel RK, Singh D, Lagunin A, Poroikov V. Pass-assisted exploration of new therapeutic potential of natural products. Med Chem Res 2011;20(9):1509-14.

About this article







Additional Links

Manuscript Submission


Asian Journal of Pharmaceutical and Clinical Research
Vol 9 Issue 5 September 2016 Page: 182-188

Print ISSN


Online ISSN



99 Views | 166 Downloads

Authors & Affiliations

Ramanathan K
VIT University

Shanthi V
VIT University

Kanika Verma
VIT University

Article Tools

Email this article (Login required)
Email the author (Login required)


  • There are currently no refbacks.