Synthesis and biological activity of a novel series of 6,7-dimethoxyquinazoline-2,4(1H,3H)-dione derivatives.

The heterocyclic compounds are very important part of medicinal chemistry, among them it is worth to pay attention on derivatives of quinazoline. They have a broad spectrum of pharmacological activities like anticancer (1ñ3), anti-HIV (3), antitubercular (4), anti-inflammatory (5), anticonvulsant (6) and antihypertensive activity (7). The most recognized derivatives among quinazolines with antihypertensive activity are bunazosin or alfuzosin. Moreover, it was also reported that quinazolines have an interesting antimicrobial activity against different species of pathogenic Gpositive bacteria, G-negative bacteria and fungi (8ñ12). Generally, it seems that quinazoline combined with different type of aryl, heteryl as well as alkyl substituents showed awide range of pharmacological applications. In our earlier work, we also showed that compounds containing short amine fragments exhibit antibacterial and antifungal activity (13, 14). Therefore, it was assumed that compounds having quinazoline residue in the molecule condensed with short alkyl amine may possess some interesting biological activity. In light of this information, we have decided to continue the study on the microbial activity of imide moiety condensed with short amine. This work represents a continuation of our systematic studies of compounds condensed with short alkylamine as anticancer and antibacterial agents. The starting material ñ 6,7-dimethoxyquinazoline-2,4(1H,3H)-dione, was converted into N,Nídialkylamine derivatives by using appropriate chloroalkylamines. Scheme 1 explains the method of preparation of derivatives mentioned in the title of this work. Next, all derivatives were tested for antimicrobial activity against a selection of G-positive, G-negative bacteria, yeasts and also the chosen compounds (II, IV) were tested for their cytotoxic properties in K562, HeLa and normal cells. The results are presented in Table 1. SYNTHESIS AND BIOLOGICAL ACTIVITY OF A NOVEL SERIES OF 6,7-DIMETHOXYQUINAZOLINE-2,4(1H,3H)-DIONE DERIVATIVES