Title:Privileged 1,2,4-Oxadiazoles in Anticancer Drug Design: Novel 5- Aryloxymethyl-1,2,4-oxadiazole Leads for Prostate Cancer Therapy
VOLUME: 13 ISSUE: 3
Author(s):Alexey Lukin, Ruben Karapetian, Yan Ivanenkov and Mikhail Krasavin
Affiliation:Institute of Chemistry, Saint Petersburg State University, 26 Universitetskii Prospect, Peterhof 198504 Russian Federation.
Keywords:1, 2, 4-oxadiazoles, privileged structures, prostate cancer, DU-145 cell line, hit rate, tubulin inhibitors, colchicines
binding site, in silico docking.
Abstract:Based on the structure of the previously identified leads, new series of compounds containing 1,2,4-oxadiazole
core was designed. A small, diverse library of 51 compounds including both 2-(acylamino)ethyl and 2-ureidoethyl side
chains was synthesized using parallel chemistry and tested for antiproliferative activity against prostate cancer DU-145
cell line. Four hit compounds – all belonging to 2-ureidoethyl series – were identified and three compounds were confirmed
as 10-20 µM inhibitors. The similarity in compounds’ periphery and the data obtained previously suggest a similar
mode of action for these compounds which was postulated as tubulin inhibition and was confirmed by in silico docking.
These data provide further evidence for the privileged character of 1,2,4-oxadiazoles in antiproliferative compound design.
