Poster presentation
151
MOLECULAR DOCKING BASED BINDING ENERGIES OF SOME
O-ALKYL DERIVATIVES OF GOSSYPOL
S. Yuldasheva
1,2
, M. Uktamova
1,2
, A.G. Eshimbetov
2
, K.U. Khodjaniyazov
1,2
1) National University of Uzbekistan, Tashkent, Uzbekistan
2) Institute of Bioorganic Chemistry, Tashkent, Uzbekistan
e-mail: hamidkhodjaniyazov@yandex.ru
Gossypol is a natural product with binaphthol-aldehyde chemical behavior. Gossypol
exists in three tautomeric forms: aldehyde, ketol, and lactol. Only two of the six
phenolic hydroxyls may not be affect by these transformations. These are precisely the
hydroxyl groups of the gossypol molecule on the 6,6
-positions. Overexpression of
epidermal growth factor receptor is known to be involved in the pathogenesis of non-
small cell lung cancer (NSCLC). The resistance mutation EGFR
L858R=T790M
reduced the
effectiveness of EGFR inhibitors used in clinical practice. It was shown that gossypol
inhibited cell proliferation and induced apoptosis of NSCLC cells by targeting
EGFR
L858R=T790M
. In addition, other proteins such as human neutrophil elastase (HNE),
matrix metalloproteinases (MMP 2 and 9) and tyrosinase are also involved to assess
anticancer activity. Therefore, we subjected gossypol and its alkyl derivatives on these
positions for molecular docking (MD) calculations to assessment binding energies after this
type chemical transformation. Chemical structures of ligands, i.e. gossypol (G), its
O
6-mono-
and
O
6,
O
6
-di-alkyl derivatives [alkyl is –CH
2
-COX (X=OH, NH
2
)] were constructed and 3D
structures optimized using Avogadro software and subjected to MD calculations on CB-dock.
The protein structures were edited by deleting all water molecules and co-crystallized ligands.
Docking scores (kcal/mol) were shown in the following table.
Table
Substance
Protein (or Enzyme) purified from water and ligands
4RJ8
1H1B
1QIB
4H1Q
2Y9W
Gossypol
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