1228589-93-2Relevant academic research and scientific papers
Non-classical antifolates. Part 2: Synthesis, biological evaluation, and molecular modeling study of some new 2,6-substituted-quinazolin-4-ones
Al-Omary, Fatmah A.M.,Abou-zeid, Laila A.,Nagi, Mahmoud N.,Habib, El-Sayed E.,Abdel-Aziz, Alaa A.-M.,El-Azab, Adel S.,Abdel-Hamide, Sami G.,Al-Omar, Mohamed A.,Al-Obaid, Abdulrahman M.,El-Subbagh, Hussein I.
experimental part, p. 2849 - 2863 (2010/07/02)
A new series of 2,6-substituted-quinazolin-4-ones was designed, synthesized, and evaluated for their in vitro DHFR inhibition, antimicrobial, and antitumor activities. Compounds 22, 33-37, 39-43, and 45 proved to be active DHFR inhibitors with IC50 range of 0.4-1.0 μM. Compound 18 showed broad-spectrum antimicrobial activity comparable to the known antibiotic gentamicin. Compounds 34 and 36 showed antitumor activity at GI50 (MG-MID) concentrations of 11.2, and 24.2 μM, respectively. Molecular modeling study including flexible alignment; electrostatic, hydrophobic mappings; and pharmacophore prediction were performed. A main featured pharmacophore model was developed which justifies the importance of the main pharmacophoric groups as well as of their relative distances. The substitution pattern and spatial considerations of the π-systems in regard to the quinazoline nucleus proved critical for biological activity.
