| dc.description.abstract | A significant amount of research has been done on plants of Kenya resulting in the
isolation of thousands of natural products, but data on these natural products is not
systematically organized in a readily accessible form. This has necessitated the
construction of a web-based database of natural products of Kenya. The database is
named mitishamba and is hosted at http://mitishamba.uonbi.ac.ke.
The mitishamba database was queried for chromones, chromanones and chalcones
that were subjected to structure based drug design using Fred (OpenEye) docking
utility program with 1TV5 PDB structure of the PfDHODH receptor to identify
ligands that bind with the active site. Ligand-based drug design (Shape and
electrostatics comparison) was also done on the ligands against query A77 1726 (38)
(the ligand that co-crystallized with PfDHODH receptor) using ROCS and EON
programs, respectively, of OpenEye suite. There was an above average similarity
among the top performing ligands in the docking studies with shape and electrostatic
comparison. This led to the identification of compounds of interest which were
targeted for synthesis and antiplasmodial assay.
A chromanone, 7-hydroxy-2-(4-methoxyphenyl) chroman-4-one (48) and two
intermediate chalcones, 2’,4’-dihydroxy-4-methoxychalcone (45) and 2’,4’-
dihydroxy-4-chlorochalcone (47), were synthesized and subjected to antiplasmodial
assay. Whereas 45 showed strong activity, 47 and 48 had moderate activity against
the chloroquine resistant K1 strain of P. falciparum with IC50 values of 4.56±1.66,
17.62 ± 5.94 and 18.01 ±1.66 μg/ml, respectively. Since the synthesized compounds
showed antiplasmodial potential, there is need for further computational refinement of
these compounds to optimize their antiplasmodial activity. | en_US |
