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New chemotypes for wALADin1-like inhibitors of delta-aminolevulinic acid dehydratase from Wolbachia endobacteria |
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| Authors: | Christian S. Lentz Dagmar Stumpfe Juergen Bajorath Michael Famulok Achim Hoerauf Kenneth M. Pfarr |
| Affiliation: | 1. Institute of Medical Microbiology, Immunology and Parasitology, University Hospital of Bonn, Sigmund-Freud Str. 25, 53127 Bonn, Germany;2. Department of Life Science Informatics, B-IT, LIMES, Program Unit Medicinal Chemistry and Chemical Biology, Universität Bonn, Dahlmannstr. 2, 53113 Bonn, Germany;3. LIMES Institute, Chemical Biology & Medicinal Chemistry Unit, Universität Bonn, Gerhard-Domagk-Str. 1, 53121 Bonn, Germany |
| Abstract: | Substituted benzimidazoles of the wALADin1-family have recently been identified as a new class of species-selective inhibitors of delta-aminolevulinic acid dehydratase (ALAD) from Wolbachia endobacteria of parasitic filarial worms. Due to its Wolbachia-dependent antifilarial activity, wALADin1 is a starting point for the development of new drugs against filarial nematodes. We now present several other chemotypes of ALAD inhibitors that have been identified based upon their molecular similarity to wALADin1. A tricyclic quinoline derivative (wALADin2) with a different inhibitory mechanism and improved inhibitory potency and selectivity may represent an improved drug lead candidate. |
| Keywords: | Delta-aminolevulinic acid dehydratase Heme biosynthesis wALADin |
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