Decaprenyl-phosphoryl-ribose 2'-epimerase (DprE1): challenging target for antitubercular drug discovery

Abstract

Tuberculosis has proved harmful to the entire history of mankind from past several decades. Decaprenyl-phosphoryl-ribose 2'-epimerase (DprE1) is a recent target which was identified in 2009 but unfortunately it is neither explored nor crossed phase II. In past several decades few targets were identified for effective antitubercular drug discovery. Resistance is the major problem for effective antitubercular drug discovery. Arabinose is constituent of mycobacterium cell wall. Biosynthesis of arabinose is FAD dependant two step epimerisation reaction which is catalysed by DprE1 and DprE2 flavoprotein enzymes. The current review is mainly emphases on DprE1 as a perspective challenge for further research.

Keywords: Antitubercular agents; Covalent and non covalent inhibitors; DprE1; Future needs.

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Benzothiazinones

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Dinitrobenzamides

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PBTZ169

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VI-9376

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377790

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Benzothiazole-N-oxide

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6-Methyl-7-nitro-5-(trifluoromethyl)-1,3-benzothiazoles

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TCA 1

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TBA-7371 (1–4 azaindoles)

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TBA-7371 (1–4 azaindoles)

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PyrBTZ02 (8-pyrrole-BTZ)

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1,2,4-Triazole containing 1,4-BTZ derivatives (cmp-6c)

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1,3-BTZ azide

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Benzothiazolylpyrimidine-5-carboxamides (cmp-7a)

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Pyrazolopyridones (cmp-19)