title: Screening of potential targets in Plasmodium falciparum using stage-specific metabolic network analysis.
abstract: The Apicomplexa parasite Plasmodium is a major cause of death in developing countries which are less equipped to bring new medicines to the market. Currently available drugs used for treatment of malaria are limited either by inadequate efficacy, toxicity and/or increased resistance. Availability of the genome sequence, microarray data and metabolic profile of Plasmodium parasite offers an opportunity for the identification of stage-specific genes important to the organism's lifecycle. In this study, microarray data were analysed for differential expression and overlapped onto metabolic pathways to identify differentially regulated pathways essential for transition to successive erythrocytic stages. The results obtained indicate that S-adenosylmethionine decarboxylase/ornithine decarboxylase, a bifunctional enzyme required for polyamine synthesis, is important for the Plasmodium cell growth in the absence of exogenous polyamines. S-adenosylmethionine decarboxylase/ornithine decarboxylase is a valuable target for designing therapeutically useful inhibitors. One such inhibitor, [Formula: see text]-difluoromethyl ornithine, is currently in use for the treatment of African sleeping sickness caused by Trypanosoma brucei. Structural studies of ornithine decarboxylase along with known inhibitors and their analogues were carried out to screen drug databases for more effective and less toxic compounds.
authors: Ashok and Rita Patel Institute of Integrated Study and Research in Biotechnology and Allied Sciences (ARIBAS), New Vallabh Vidyanagar, Anand, Gujarat, 388121, India.
authors: Neel
authors: N
authors: Dholakia
authors: Ashok and Rita Patel Institute of Integrated Study and Research in Biotechnology and Allied Sciences (ARIBAS), New Vallabh Vidyanagar, Anand, Gujarat, 388121, India. pinakindhandhukia@aribas.edu.in.
authors: Pinakin
authors: P
authors: Dhandhukia
authors: Ashok and Rita Patel Institute of Integrated Study and Research in Biotechnology and Allied Sciences (ARIBAS), New Vallabh Vidyanagar, Anand, Gujarat, 388121, India.
authors: Nilanjan
authors: N
authors: Roy
mesh_terms: D012437:Adenosylmethionine Decarboxylase / Q000037:antagonists & inhibitors / Q000737:chemistry; D000962:Antimalarials / Q000737:chemistry* / Q000494:pharmacology; D015195:Drug Design; D005786:Gene Expression Regulation; D006801:Humans; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D020411:Oligonucleotide Array Sequence Analysis; D009955:Ornithine Decarboxylase / Q000737:chemistry; D010802:Phylogeny; D010963:Plasmodium falciparum / Q000187:drug effects / Q000201:enzymology* / Q000254:growth & development*; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D000962:Antimalarials; D015800:Protozoan Proteins; D009955:Ornithine Decarboxylase; D012437:Adenosylmethionine Decarboxylase
keywords: Comparative docking; Computer- aided drug design; In silico drug design; Malaria; Ornithine decarboxylase; Plasmodium falciparum