Leishmania donovani

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• 作者：Pranav Kumar ; Ashutosh Kumar ; Shyam Sundar Verma ; Namrata Dwivedi ; Nasib Singh ; Mohammad Imran Siddiqi ; Rama Pati Tripathi ; Anuradha Dube ; Neeloo Singh
• 刊名：Experimental Parasitology
• 出版年：2008
• 出版时间：September 2008
• 年：2008
• 卷：120
• 期：1
• 页码：73-79
• 全文大小：1413 K

文摘

Pteridine reductase 1 (PTR1, EC 1.5.1.33) is a NADPH dependent short-chain reductase (SDR) responsible for the salvage of pterins in the protozoan parasite Leishmania. This enzyme acts as a metabolic bypass for drugs targeting dihydrofolate reductase, therefore, for successful antifolate chemotherapy to be developed against Leishmania, it must target both enzyme activities. Based on homology model drawn on recombinant pteridine reductase isolated from a clinical isolate of L. donovani, we carried out molecular modeling and docking studies with two compounds of dihydrofolate reductase specificity showing promising antileishmanial activity in vitro. Both the inhibitors appeared to fit well in the active pocket revealing the tight binding of the carboxylic acid ethyl ester group of pyridine moiety to pteridine reductase and identify the important interactions necessary to assist the structure based development of novel pteridine reductase inhibitors.