6,7-Dimethoxyquinazolines as Potential Cytotoxic Agents: Synthesis and in vitro Activity

作者：Yadav Mange Ram^*; Chauhan Bishram Singh; Naik Prashant; Gandhi Hardik; Giridhar Rajani

来源：Letters in Drug Design and Discovery, 2015, 12(3): 190-205.

• Anti-cancer agents
• cancer
• cytotoxicity
• quinazoline
• quinazolinone

It has been reported that 6,7-dimethoxyquinazoline derivatives have cytotoxic potential independent of their alpha(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 n-butyl 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.

• 出版日期2015