DESIGN OF HYDROXY XANTHONES DERIVATIVES AS ANTICANCER USING QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP
Abstract
ABSTRACT
Objective: The objective of the research is to design a new hydroxy xanthone derivative has anticancer activity using quantitative structure-activity
relationship (QSAR).
Methods: The QSAR designed new compounds were calculated by parameterized model 3 methods and analysis of multi-linear regression (MLR).
Result: The result showed that the best model as follows:
LogIC
= –9.132 qC1 + 28.853 qC5 + 2.456 qC6 – 7.375 qC10 – 5.112 qC11 + 3.900
This result has appropriate some statistical parameters (n=24; PRESS=0.999; r
50
2
=0.782; SEE=0. 235; R=0. 885; F
cal
/F
Conclusion: This Model could be used to design of halogen-substituted hydroxy xanthone scaffold and predict their inhibitory concentration (IC
tab
=4.68).
) as
anticancer in the range of 0.001 - 0.484 μM.
Keywords: Anticancer, Quantitative structure-activity relationship, Xanthone.
50
Downloads
References
REFFERENCES
Heffeter P, Jakupec MA, Körner W, Chiba P, Pirker C, Dornetshuber R,
et al. Multidrug-resistant cancer cells are preferential targets of the
new antineoplastic lanthanum compound KP772 (FFC24). Biochem
Pharmacol 2007;73(12):1873-86.
Khonkarn R, Mankhetkorn S, Talelli M, Hennink WE, Okonogi S.
Cytostatic effect of xanthone-loaded mPEG-b-p(HPMAm-Lac2)
micelles towards doxorubicin sensitive and resistant cancer cells.
Colloids Surf B Biointerfaces 2012;94:266-73.
Iranshahi M, Sahebkar A, Hosseini ST, Takasaki M, Konoshima T,
Tokuda H. Cancer chemopreventive activity of diversin from Ferula
diversivittata in vitro and in vivo. Phytomedicine 2010;17(3-4):269-73.
Tsuruo T. Molecular cancer therapeutics: Recent progress and targets in
drug resistance. Intern Med 2003;42(3):237-43.
Li R, Hehlman R, Sachs R, Duesberg P. Chromosomal alterations cause
the high rates and wide ranges of drug resistance in cancer cells. Cancer
Genet Cytogenet 2005;163(1):44-56.
Shi LM, Fan Y, Myers TG, O’Connor PM, Paull KD, Friend SH, et al.
Mining the NCI anticancer drug discovery databases: Genetic function
approximation for the QSAR study of anticancer ellipticine analogues.
J Chem Inf Comput Sci 1998;38(2):189-99.
Oloff S, Mailman RB, Tropsha A. Application of validated QSAR
models of D1 dopaminergic antagonists for database mining. J Med
Chem 2005;48(23):7322-32.
Meneses-Marcel A, Marrero-Ponce Y, Machado-Tugores Y, MonteroTorres
A,
Pereira
DM, Escario
JA, et
al. A
linear
discrimination analysis
based
virtual screening
of trichomonacidal
lead-like
compounds:
Outcomes of in silico studies supported by experimental results. Bioorg
Med Chem Lett 2005;15(17):3838-43.
Santana L, Uriarte E, González-DÃaz H, Zagotto G, Soto-Otero R,
Méndez-Alvarez E. A QSAR model for in silico screening of MAO-A
inhibitors. Prediction, synthesis, and biological assay of novel
coumarins. J Med Chem 2006;49(3):1149-56.
Alam S, Khan F. QSAR and docking studies on xanthone derivatives
for anticancer activity targeting DNA topoisomerase IIa. Drug Des
Devel Ther 2014;8:183-95.
Amanatie A, Jumina J, Mustofa M, Hanafi M, Armunanto R. QSAR
study of xanthone derivatives as antiplasmodial agent. Indones J Chem
;10:357-62.
Suphavanich K, Maitarad P, Hannongbua S, Sutda P, Suksamrarmn S,
Tantirungrotechai Y, et al. CoMFA an CoMSIA study on a new series
of xanthone derivatives against the oral human epidomoid carcinoma
(KB) cancer cell line. Monatash Chem 2009;140:273-80.
Cui J, Hu W, Cai Z, Liu Y, Li S, Tao W, et al. New medicinal properties
of mangostins: Analgesic activity and pharmacological characterization
of active ingredients from the fruit hull of Garcinia mangostana L.
Pharmacol Biochem Behav 2010;95(2):166-72.
Jung HA, Su BN, Keller WJ, Mehta RG, Kinghorn AD. Antioxidant
xanthones from the pericarp of Garcinia mangostana (Mangosteen).
J Agric Food Chem 2006;54(6):2077-82.
Cheng JH, Huang AM, Hour TC, Yang SC, Pu YS, Lin CN. Antioxidant
xanthone derivatives induce cell cycle arrest and apoptosis and enhance
cell death induced by cisplatin in NTUB1 cells associated with ROS.
Eur J Med Chem 2011;46(2):1222-31.
Nakatani K, Atsumi M, Arakawa T, Oosawa K, Shimura S,
Nakahata N, et al. Inhibitions of histamine release and prostaglandin
E2 synthesis by mangosteen, a Thai medicinal plant. Biol Pharm Bull
;25(9):1137-41.
Sakagami Y, Iinuma M, Piyasena KG, Dharmaratne HR. Antibacterial
activity of alpha-mangostin against vancomycin resistant
Enterococci (VRE) and synergism with antibiotics. Phytomedicine
;12(3):203-8.
Suksamrarn S, Suwannapoch N, Phakhodee W, Thanuhiranlert J,
Ratananukul P, Chimnoi N, et al. Antimycobacterial activity of
prenylated xanthones from the fruits of Garcinia mangostana. Chem
Pharm Bull (Tokyo) 2003;51(7):857-9.
Kaomongkolgit R, Jamdee K, Chaisomboon N. Antifungal activity of
alpha-mangostin against Candida albicans. J Oral Sci 2009;51(3):401-6.
Chen LG, Yang LL, Wang CC. Anti-inflammatory activity of mangostins
from Garcinia mangostana. Food Chem Toxicol 2008;46(2):688-93.
Matsumoto K, Akao Y, Kobayashi E, Ohguchi K, Ito T, Tanaka T,
et al. Induction of apoptosis by xanthones from mangosteen in human
leukemia cell lines. J Nat Prod 2003;66(8):1124-7.
Aisha AF, Abu-Salah KM, Ismail Z, Majid AM. In vitro and in vivo
anti-colon cancer effects of Garcinia mangostana xanthones extract.
BMC Complement Altern Med 2012;12:104.
Su QG, Liu Y, Cai YC, Sun YL, Wang B, Xian LJ. Anti-tumour effects
of xanthone derivatives and the possible mechanisms of action. Invest
New Drugs 2011;29(6):1230-40.
Kuete V, Sandjo LP, Ouete JL, Fouotsa H, Wiench B, Efferth T.
Cytotoxicity and modes of action of three naturally occurring xanthones
(8-hydroxycudraxanthone G, morusignin I and cudraxanthone I) against
sensitive and multidrug-resistant cancer cell lines. Phytomedicine
;21(3):315-22.
Luo L, Qin K, Dai ZK, Gou SH. Synthesis and biological evaluation
of novel benzo [b] xanthone derivatives as potential antitumor agents.
J Serbian Chem Soc 2013;78:1301-8.
Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA,
Cheeseman JR, et al. Gaussian 09, Revision A.02. Wallingford, CT:
Gaussian, Inc.; 2009.
Yee BJ. Chemical synthesis of 1,6 dioxygenated xanthones and their
cytotoxic activities. B. Sc Degree, Faculty of Science, Universiti
Tungku Abdul Rahman; 2011.
Jain SV, Ghate M, Bhadoriya KS, Bari SB, Chaudhari A, Borse JS.
D, 3D-QSAR and docking studies of 1,2,3-thiadiazole thioacetanilides
analogues as potent HIV-1 non-nucleoside reverse transcriptase
inhibitors. Org Med Chem Lett 2012;2(1):22.
Podunavac-Kuzmanovic SO, Cvetkovic DD, Barna DJ. QSAR
analysis of 2-amino or 2-methyl-1-substituted benzimidazoles against
Pseudomonas aeruginosa. Int J Mol Sci 2009;10(4):1670-82.
Golbraikh A, Shen M, Xiao Z, Xiao YD, Lee KH, Tropsha A. Rational
selection of training and test sets for the development of validated
QSAR models. J Comput Aided Mol Des 2003;17(2-4):241-53.
Modak VP, Pathak H, Thayer M, Singer SJ, Wyslouzil BE. Experimental
Asian J Pharm Clin Res, Vol 9, Issue 2, 2016, 180-185
Yuanita et al.
evidence for surface freezing in supercooled n-alkane nanodroplets.
Phys Chem Chem Phys 2013;15(18):6783-95.
Motta LF, Almeida WP. Quantitative structure-activity relationships
(QSAR) of a series of ketone derivatives as anti-Candida albicans. Int J
Drug Disc 2011;3:100-17.
Frimayanti N, Yam ML, Lee HB, Othman R, Zain SM, Rahman NA.
Validation of quantitative structure-activity relationship (QSAR)
model for photosensitizer activity prediction. Int J Mol Sci
;12(12):8626-44.
Mudasir M, Wibowo YM, Pranowo HD. Design new potent insecticides
of organophosphate derivatives based on QSAR Analysis. Indones J
Chem 2013;13(1):86-93.
Woo S, Jung J, Lee C, Kwon Y, Na Y. Synthesis of new xanthone
analogues and their biological activity test – Cytotoxicity,
topoisomerase II inhibition, and DNA cross-linking study. Bioorg Med
Chem Lett 2007;17(5):1163-6
Published
How to Cite
Issue
Section
The publication is licensed under CC By and is open access. Copyright is with author and allowed to retain publishing rights without restrictions.