ANALISIS IN SILICO GENISTEIN DAN ANALOGNYA SEBAGAI INHIBITOR KANKER PAYUDARA RESEPTOR ESTROGEN ALFA POSITIF (ERα+)
ABSTRACT: Breast cancer is the
highest mortality disease on women in the world and about 60-80% of the cases
are ERα+ breast cancer. The discovery of more selective to HERα, safe, and
potential new anticancer agent is expected to help the treatment of ERα+ breast
cancer. In silico analysis had been carried out by computational chemistry methods,
including determination of physicochemical parameters such as
lipophilicity/CLogP, molar refractivity/CMR, bond energy/HOMO-LUMO and E-Gap,
partial charge reactivity; determination of structural similarity by
overlaying, and the interaction analysis of genistein and its analogues against
HERα by docking method. The result showed that group of -7OH on the C ring and
group of -4'OH on the A ring of genistein were the major pharmacophore. More
number of hydrogen bonds (especially to Arg394), shorter distance, and lower free
binding energy resulted higher inhibitory activity, it was shown by MA6 which
had 4 of hydrogen bonds (-14,51 kcal/mol) and each of them bound to Arg394 (=N-
aromatic, substituent of -4'OR), Arg394 (-4'OR), His524 (-7OR), and Leu391 (=N-
aromatic, substituent of -4'OR). Genistein, MA6, and MA8 had similar activity
to tamoxifen even predicted more potent (MA6), it was correlated to its binding
with Arg394. The complete result of in silico analysis confirmed the activity
of genistein and its analogues as an inhibitor of ERα+ breast cancer.
Penulis: Fauzan Zein M, Rika
Andriani, Sophi Damayanti
Kode Jurnal: jpfarmasidd150263
