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NISCAIR ONLINE PERIODICALS REPOSITORY (NOPR) >
NISCAIR PUBLICATIONS >
Research Journals >
Indian Journal of Biochemistry and Biophysics (IJBB) >
IJBB Vol.49 [2012] >
IJBB Vol.49(2) [April 2012] >
| Title: | Pharmacophoric studies of in vitro inhibition of Plasmodium falciparum growth |
| Authors: | Hariharan, Sivaram |
| Keywords: | Bisphosphonates
3D-QSAR
Pharmacophore
PHASE
Plasmodium falciparum
Antimalarials |
| Issue Date: | Apr-2012 |
| Publisher: | NISCAIR-CSIR, India |
| Abstract: | Malaria continues to be a scourge in India and the situation has been
compounded by the emergence of resistant strains of Plasmodium falciparum which
is the primary cause of fatality in this disease. Therefore, there is an
urgent need to develop newer drugs. Molecular modeling and pharmacophoric
determination have become predominant methods today in the design and synthesis
of newer and more effective drugs. Many Plasmodium specific enzymes and
proteins involved in crucial biochemical pathways have been identified and
their structures have been determined by X-ray crystallography. These enzymes
and proteins are excellent targets for newer antimalarial agents.
Bisphosphonates have shown potent inhibitory activity against Plasmodium
farneysl diphosphate synthase (FPPS) enzyme, which is vital to the protein
prenylation pathway of the organism. In this study, a set of 26 bisphosphonate
inhibitors, synthesized by Oldfield et al
[J Med Chem (2008) 51, 7827-7833]
were subjected to rigorous 3D-QSAR studies using the PHASE computational package.
In vitro Plasmodium growth inhibition rather than direct enzyme inhibition
was considered in the study for a more realistic approach. Good statistical
correlations were obtained for the pharmacophoric model as revealed by the
regression values, indicating good stability of the model. Three hydrogen bond
acceptors and a hydrogen bond donor defined the pharmacophore from the present
study. This pharmacophore, AAAD (A = Hydrogen bond acceptor and D = Hydrogen
bond donor) was put through a search-run for matching structures from the SPECS
database yielding four matching structures, which could function as starting
points for more novel and potent antimalarials. |
| Page(s): | 101-108 |
| CC License: |  CC Attribution-Noncommercial-No Derivative Works 2.5 India |
| ISSN: | 0975-0959 (Online); 0301-1208 (Print) |
| Source: | IJBB Vol.49(2) [April 2012]
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