Synthesis and Biological Evaluation of Quinazolinone Derivatives as Antibacterial and Anti-Inflammatory Agents

There is a strong relationship between bacterial infection and inflammation (Sy et al., 2011). Bacterial infection often produces pain and inflammation. Inflammation remains a com- mon with poorly controlled clinical problem which can be life threatening in extreme form of allergy, autoimmune diseases and rejection of transplanted organs (Gounon and Huerre, 1996). The treatment options which can be used for inflammatory diseases are unsatisfactory and complicated due to their lack of efficacy and adverse effect profile. It seemed worthwhile to look for candidates acting on more than one path- way involved in inflammatory conditions (Bot et al., 2011).

Quinazolin-4-one ring system has been consistently re- warded as a promising molecule because of its broad spectrum of pharmaceutical activities like antihistaminic (Lemura et al., 1989), anti inflammatory (Amin et al., 2010), antibacterial (Kini and Grover, 2006), antidiabetic (Ram et al., 2003), anti- cancer (Abbas et al., 2012), antifungal (Liu et al., 2006), anthelmintics (Connolly et al., 2005) and antiviral activities (Dinakaran et al., 2003). In addition to that, anti-inflammatory quinazolines possess remarkable anti-inflammatory activity through inhibition of tumor necrosis factor-alpha (TNF-a) and interleukin-6 (IL-6) (Rajan et al., 2010).

On the other hand, sulfonamide derivatives have been reported to possess significant antibacterial activities through competitive inhibition of dihydropteroate synthetase enzyme (DHPS) which is involved in folate synthesis (Skold, 2000). Moreover, some sulfonamides work as anti-inflammatory drugs like celecoxib which works as a COX-2 inhibitor (Gassani et al., 2010) and acetazolamide which works by diuretic mechanism (Jaiswal et al., 2004). On light of these findings, we planned to prepare the target com- pounds as hybrid molecules. These molecules contain the quinazolinone ring system and fused with sulfonamide derivatives to form a group of compounds resembling and collecting both features of nitrogen heterocyclic moiety and sulfonamide moiety. In addition, iodine atoms exist at 6th and 8th positions from quinazoline nucleus. Iodine was selected because it has received consider- able attention in organic synthesis due to its high tolerance to air and moisture, low-cost, nontoxic nature and ready availability. Presence of iodine increases the lipophilicity of the molecules, the surface of contact, the absorption and the distribution (Laznicek et al., 1985; Yanming et al., 2003).