Title:6,7-Dimethoxyquinazolines as Potential Cytotoxic Agents: Synthesis and in vitro Activity
Volume: 12
Issue: 3
Author(s): Mange Ram Yadav, Bishram Singh Chauhan, Prashant Naik, Hardik Gandhi and Rajani Giridhar
Affiliation:
Keywords:
Anti-cancer agents, cancer, cytotoxicity, quinazoline, quinazolinone.
Abstract: It has been reported that 6,7-dimethoxyquinazoline derivatives have cytotoxic potential independent of their 1-
adrenoceptor blocking potential. Bioisosteres of 2-arylquinazolines are considered to have anti-tumor properties. In the
present study, we have synthesized the 2-aryl and 2-arylmethyl derivatives of quinazolin-4(3H)-one while retaining the
6,7-dimethoxy substituents. Derivatives with n-butyl group attached to position-3 of quinazolinone nucleus were synthesized
with the aim of increasing their lipophilicity. The potential of these synthesized compounds was evaluated against
NCI (National Cancer Institute) 60 cell panel using the NCI disease oriented antitumor screen protocol. Based on the results
of this screening we generalized that compounds having aryl groups directly attached to the quinazoline ring are less
active than those which have one atom linker in between the two ring systems. Substitution of a lipophilic group like nbutyl
decreases cytotoxic activity among the compounds and 4-aminoquinazolines showed better activity than 4-
quinazolinones. Lipophilic groups in the aromatic ring yielded more active compounds as cytotoxic agents. Among the selected
compounds, 4h and 13b were found to be potential lead compounds which could be further optimized as potential
anti-neoplastic agents.
