Structure based designing and ADME-T studies of butenolide derivatives as potential agents against receptor ICAM-1: A drug target for cerebral malaria

• Detailed mechanism of pathogenesis of cerebral malaria was studied, which revealed that protein receptor ICAM-1 is the main host receptor involved in the cytoadherence of infected erythrocytes to the brain venules.
• Compounds having potency to inhibit the cytoadherence may limit the sequestration of brain in cerebral malaria.
• A library of 44 hypothetical butenolide based hits was evaluated as ICAM-1 receptor inhibitors using in silico approaches of molecular docking and ADME-T predictions.
• Binding modes of hypothetical hits were compared with drug Artesunate.
• Finally the whole effort leads to total nine most promising analogues (1c, 2b, 2c, 2d, 2h, 3c, 3d, 3i and 4d) which can be explored further as a template to design more potential agents against cerebral malaria.

An attempt toward designing of some butenolide derivatives against Cerebral Malaria (CM), as inhibitors of Intercellular adhesion molecule- 1(ICAM-1) was carried out using in silico approaches of molecular docking studies. ADME-T studies were also performed to further optimize the ligands. Binding conformations were compared with Artesunate, the main drug used in treatment of CM, the designed ligands exhibited comparative binding with artesunate. Finally the whole effort leads to total nine most promising analogues (1c, 2b, 2c, 2d, 2h, 3c, 3d, 3i and 4d) which can be explored further as a template to design more potential agents against cerebral malaria.