Abstract
The synthesis of some new 2-thieno-4(3
H)-quinazolinone derivatives and their biological evaluation as antitumor agents using the National Cancer Institute (NCI) disease oriented antitumor screen protocol are investigated. Compounds 2-(2-thienylcarbonylamino)-5-iodo-
N-(4-hydroxyphenyl)-benzamide (
16), 2-(2-thieno)-6-iodo-3-phenylamino-3,4-dihydro-quina-zolin-4-one (
26), and 2-(2-thieno)-4-[4-sulfonamidobenzylamino]-6-iodo-quinazoline (
42), with GI
50 values of 12.7, 10.3, 16.9
μM, respectively, proved to be the most active members in this study, as compared to the known drug 5-FU. Conformational analysis of the most active molecules using molecular modeling and QSAR techniques enabled the understanding of the pharmacophoric requirements for 2-thieno-quinzolinone derivatives as antitumor agents. These three quinazolinone analogs (
16,
26,
42) could be considered as useful templates for future development to obtain more potent antitumor agents.
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