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MOLECULAR DOCKING STUDIES OF AGLYCONE CURCULIGOSIDE A AND

ITS DERIVATIVES WITH HER- RECEPTOR


Mariana Jamco, Megawaty, and Nursamsiar
Sekolah Tinggi Ilmu Farmasi Makassar, Jalan P. Kemerdekaan Km 13.7 Daya, South Sulawesi, Indonesia
e-mail: n.siar@yahoo.co.id

ABSTRAK
The estrogen receptor-alpha is a wonderfully complex protein important in normal biology, breast cancer, and as a target for
anti-cancer agents. The aim of the present study was intended to obtain the information of the interaction of aglycone
curculigoside A and its derivatives with HER- receptor in design of new related anticancer. Docking simulations were performed
by AutoDock 4.2. Aglycone curculigoside A and its derivatives were docked into binding site of receptor HER-. The docking
r esults revealed that aglycone curculigoside A and its derivatives can interact with receptor binding sites. Compound 3
(3,5-dihydroxybenzyl-3,5-dihydroxybenzoate) and 30 (3,5-dihydroxybenzyl-3-nitrobenzoate) exhibited better binding interaction
with free energy of binding (FEB) -7.89 kcal/mol and -7.84 kcal/mol, respectively. Upon interaction HER- with compound 3 forms
hydrogen bonds to Glu419, Gly521, Glu353, Leu346, and His524, while interaction with compound 30 showed hydrogen binding
to Glu353, Leu346, Arg394, His524, and Leu525 residues. Moreover, they have the same pattern of hydrogen bonds with the
known binding ligand (Tamoxiphen) for HER-.

Keywords: Aglycone curculigoside A, HER-, Molecular Docking

INTRODUCTION EXPERIMENTAL
Cancer is a disease characterized by the disturbance or failure
in multiplication regulating mechanisms and other homeostatic functions
in multicellular organisms. The estrogen receptor-alpha is a wonderfully COMPOUNDS MACROMOLECULE
complex protein important in normal biology, breast cancer, and as a target
for anti-cancer agents. Breast cancer is the second leading cause of cancer Geometric Optimization HER- (PDB ID 3ERT)
in the western countries compared to the Asian countries, and about 60% ab initio
percent of breast cancers are detected as estrogen receptor alpha positive hyperchem v8.01
(ER ) cancers. ER is essential for mammary gland development and
plays a central role in breast cancer development, but ER can mediate
VALIDATION
estrogen-induced cell proliferation in an autocrine mode in ER positive AutoDock 4.2
breast cancer cell lines. The diagnostic strategies with the highest positive
predictive value (88%) included hormone receptors (estrogen or progester-
one) and mammaglobin in serial manner .
DOCKING SIMULATION

RESULTS & DISCUSSION


AutoDock 4.2

Figure 1. Binding Interaction between Native Ligand, Compound 3 and 30 with HER-
receptors

CONCLUSIONS
Compound 3 (3,5-dihydroxybenzyl-3,5-dihydroxybenzoate) and REFERENCES
30 (3,5-dihydroxybenzyl-3-nitrobenzoate) exhibited better binding
interaction to HER- with free energy of binding (FEB) -7.89 kcal/mol [1] Greschik H., Flaig R., Renaud J.P., and Moras D., The Journal of Biological
Chemistry, 2004, 279, 33639-33646.
and 7.84 kcal/mol, respectively. they have the same pattern of [2] Skafar D.F. and Koide S., Molecular and Cellular Endocrinology, 2006, 246,
hydrogen bonds with the known binding ligand (Tamoxiphen) for HER- 83-90.
*) Presented at The 5th ICICS (International Conference of the Indonesian Chemical Society , 30 31 August, 2016, Samarinda, Indonesia

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