STRUCTURE MODIFICATION AND MOLECULAR MODELING OF 1-(BENZOYLOXY)UREA DERIVATIVES AS ANTICANCER DRUG CANDIDATES

Abstract

Structure modification made in designing new drugs,
by changing the structure of the lead compound.
Changes in the structure of a compound would alter
the physicochemical properties including lipophilic,
electronic and steric properties of the compound
(Korolkovas, 1988; Siswandono, 2014). Changes in
physicochemical properties would lead to changes in
the activity of each compound (Hardjono et al,
2016). Molecular modeling through in silico test is a
test that is done through computer simulation.
Molecular Modeling is used to predict a new drug
candidate compounds to be synthesized. This test
was performed in order to improve efficiency in the
optimization of the activity of the lead compound
(Topliss J.G., 1988, Istyastoro 2007; Jenzen 2007,
Kumar C.S, 2013, Dyah N.W., 2016).
Some derivatives of 1-(Benzoyloxy)urea showed
cytotoxic activity and predicted could be used as
anti-cancer drugs (Hardjono, 2012; Hardjono 2016).
Mechanism of action of urea derivatives including 1-
(Benzoyloxy)urea was by inhibiting the action of the
enzyme ribonucleotide reductase. This in silico test
research done by docking the compound whicg
activities to be predicted using MVD (Molegro
Virtual Docker) program. The target cell used in
docking was 2EUD, a ribonucleotide reductase
enzyme crystal I, which forms a complex with the
derivative 1-(Benzoyloxy)urea. 2EUD chosen
because it was the target cell from Gemsitabin which
work mechanism similar to urea (Xu H., 2006). From
in silico test would be obtain Rerank Score (RS)
values, which was the bond energy between the
ligands and target cell. Small RS value indicated that
the bond energy needed between the compound
with a target cell was also small. The smaller the
bond energy indicated that the bond was more
stable. The more stable binding of ligands to the
receptor, it could be predicted activity will be even
greater (Hardjono, 2012).
In this research would be done molecular modeling
of twenty-four 1-(Benzoyloxy)urea derivatives. The
in silico test result was an image that showed the
hydrogen bond, Electrocic and steric interaction as
well as the value of RS from 1-(Benzoyloxy)urea and
its derivatives. Of the entire RS values obtained
would be seen 1-(Benzoyloxy)urea derivates which
had the smallest RS value or