A new antimalarial approach for designing an anticancer regiment by in silico methods: The iron chelating multitarget hybrid HPO drivatives

Toward the design of new drugs, many efforts have been made to synthesize the analogues of a hybrid pharmacophore such as iron chelating agent such as H.PO with 4-aminoquinoline drivatives for prevention of malaria disease through inhibition of growth and nucleation the hemozoin crystal[1]. The accumulation of the CQ based scaffold in digestive vacuole and interference in the hemoglobin digestion and inhibition of the conversion of hem to hemozoin exhibits antimalarial activity[2]. The 4-HPO drivatives have similar strctures of diferiprone that has a good potential as iron chelating agent[3]. Several target proteins disturb this mechanism such as hemoglobin, β.hematin sheet, plasmepsin enzyme[4]. Reverse docking studies with GOLD algorithm, pharmacophore modeling and biological activity evaluation have been displayed multitarget action in biological pathway a typical antimalarial agent. Significantly, nonpeptidomimetic inhibitors show an interaction with hemoglobin, heme and aspartic protease, which may be improved the selectivity of the interaction. Antimalaria and anticancer mechanism of the cited compounds could be attributed to a similar way by rapid uptake and increasing the concentration of iron in cancerous cell[5] and improved the selectivity profile against human aspartic proteases[6]. In silico methods like pharmacophore modeling and protein ligand docking investigation now adays play fundamental rules for new drug design .There are several reports that used this method to revealed the exact mechanism of the protein drug interaction which is a requirement for designing of new drugs.[7]

Keywords:

Antimlaria , heme , hybrid , multitarget