الفهرس | Only 14 pages are availabe for public view |
Abstract Schistosomiasis (Bilharziasis) is an acute and chronic parasitic disease caused by blood flukes (trematode worms) of the genus Schistosoma. Molluscicides of plant origin have gained recently great attention and proved to be a good strategy for snail control. Life cycle of Schistosoma mansoni is complex and requires two hosts; a human dfinitive host and an intermediate snail host. The parasite develops from miracidia, the infective larvae of snails, to cercariae, the infective stage of human, within Biomphalaria snails. Analogs of nitrogen- based heterocycles hold a unique position in medicinal chemistry as a valuable source of therapeutic agents. Alkaloids from plants are promising compounds for searching for new drugs against infectious diseases. Quinoline is one of the pharmaceutical cores used in drug discovery. This pharmaceutical core containing N-heterocyclic has potent biological importance as an antimicrobial, antiviral, antioxidant, anti-inflammatory and anticancer agents. The present work aimed to evaluate the activity of natural product analogues derived from N-heterocycles analogues based on quinoline, acridine and neocryptolepine against S. mansoni aquatic stages and B. alexandrina snails. The mortality of snails, egg laying capacity and growth rate of exposed snails were recorded daily. The mean total numbers of hemocytes/ml, differential number and phagocytic activity were examined after 24 hours of exposure. Histological structure, total protein content and electrophoretic protein pattern in (ovotestis and digestive glands) were examined after the first and the second weeks of exposure. The results of the present study are summarized as follows: 1. Regarding to the structural modifications of naturally occurring pharmaceutical compounds, cooperation with the Department of Chemistry was achieved for synthesis and characterization of six of N-heterocycles analogues based on quinoline, acridine and neocryptolepine motifs standing for CAAQ, APACQ, AEAA and APAA. 2. Molecular docking studies were demonstrated on the six prepared compounds to investigate their affinity for cysteine protease protein. Compound AEAN showed the best binding affinities -5.9386 and -5.3160 and RMSD values of 1.4522 and 1.1881 in both proteins PDB: 2P7U and PDB: 1CJL, respectively. Compound AEAN chemical bonding and the residues involved in its interaction site with the proteins PDB: 2P7U and PDB: 1CJL. |