Design, synthesis, anti-inflammatory evaluation, and molecular docking studies of novel quinazoline-4(3<i>H</i>)-one-2-carbothioamide derivatives
Le Thanh Hang Nguyen, Vũ Đình Hoàng, Phạm Minh Quân, Quoc Anh Ngo, Ngoc Binh Vo
Abstract
, 8k), is responsible for the potent anti-inflammatory activity of these novel quinazolinone derivatives. Computational modeling studies revealed that compounds 8d, 8g, and 8k are potent inhibitors of TLR4 signaling through the formation of hydrophobic interactions and are stabilized by hydrogen bonds. Replacing the thioamide (8k) with an amide (8q) resulted in an 83-fold decrease in NO inhibitory potency. This highlights the important role of H-bonding involving the thioamide group. The structural shape difference results in favorable interactions of quinazolinones containing thioamide linkers compared to amide linkers to the target receptor. Furthermore, the ADMET profiles and physicochemical properties of these three lead compounds were predicted to meet the criteria for drug-like properties. Therefore, these compounds may be potential candidates for the treatment of many inflammatory diseases associated with immune disorders.