S. Erkoç; Synthesis of Novel Potent Drug Molecules Active... Nov. 21

SYNTHESIS OF NOVEL POTENT DRUG MOLECULES ACTIVE AGAINST PROSTATE CANCER AND CYCLOPOLYMERS OBTAINED BY CONTROLLED/LIVING POLYMERIZATION
TECHNIQUES (ATRP AND RAFT POLYMERIZATION)

Selda Erkoc
Bogazici University, Department of Chemistry, Bebek 34342, Istanbul, Turkey

Reducing the androgen level can prevent the growth of the prostate cancer cells. Strong and
selective inhibition of CYP17 enzyme (17α-hydroxylase/17,20-lyase (P450 17)) by using drug
molecules results in a complete or exclusive elimination of androgen biosynthesis. Therefore,
this enzyme has become a promising therapeutic target. Structure-based drug design approach
(SBDD) was used to discover novel lead compounds active against CYP17 enzyme and a nonsteroidal
lead compound with the IC50 value of 35.65 μM was discovered. In order to increase
the activity of the lead compound against the CYP17, lead optimization studies were done.
Firstly, lead compound derivatives were evaluated on the computer generated model of CYP17.
Then, the compounds that have favorable energy values in docking studies were synthesized to
be effective in nanomolar concentrations. As a result, a new compound with the IC50 value of 9
μM was found. The activity of this compound is about four times higher than the activity of the
lead compound.
Controlled/living polymerization techniques (ATRP and RAFT Polymerization) were used in the
cyclopolymerization of symmetrical difunctional monomers, alkyl α-(hydroxymethylacrylate)
(RHMA) ether dimers. Under tuned conditions, cyclopolymers with six-membered
tetrahydropyrane repeat units were obtained in high conversions with controlled molecular
weights and low polydispersities. The livingness of the cyclopolymers was shown through
successful block copolymerization studies.

November 21, FENS L045 from 13:40-14:30