Author(s): ElSubbagh HI, Hassan GS, ElMessery SM, AlRashood ST, AlOmary FA,
Abstract Share this page
Abstract A new series of tetrahydro-quinazoline and tetrahydro-1H-dibenzo[b,e][1,4]diazepine analogs were synthesized and tested for their DHFR inhibition and in vitro antitumor activity. Compound 35 showed a remarkable DHFR inhibitory potency (IC₅₀, 0.004 μM) which is twenty fold more active than methotrexate (MTX). Compounds 17 and 23 proved to be fifteen fold more active than the known antitumor 5-FU, with MG-MID GI₅₀, TGI, and LC₅₀ values of 1.5, 46.8, 93.3 and 1.4, 17.4, 93.3 μM, respectively. Computer modeling studies allowed the identification that methoxy and methyl substituents, the π-system of the chalcone core, the nitrogen atoms, on the dibenzodiazepine ring as pharmacophoric features essential for activity. These mark points could be used as template model for further future optimization. Copyright © 2014 Elsevier Masson SAS. All rights reserved.
This article was published in Eur J Med Chem
and referenced in Drug Designing: Open Access