Universität zu Köln

Krome, Anna K., Becker, Tim, Kehraus, Stefan, Schiefer, Andrea, Gutschow, Michael, Chaverra-Munoz, Lillibeth ORCID: 0000-0001-9624-7339, Huttel, Stephan, Jansen, Rolf, Stadler, Marc ORCID: 0000-0002-7284-8671, Ehrens, Alexandra ORCID: 0000-0002-2570-4034, Pogorevc, Domen, Muller, Rolf, Hubner, Marc P., Hesterkamp, Thomas, Pfarr, Kenneth, Hoerauf, Achim, Wagner, Karl G. ORCID: 0000-0003-2864-7191 and Konig, Gabriele M. (2022). Corallopyronin A: antimicrobial discovery to preclinical development. Nat. Prod. Rep., 39 (9). S. 1705 - 1721. CAMBRIDGE: ROYAL SOC CHEMISTRY. ISSN 1460-4752

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Abstract

Covering: August 1984 up to January 2022 Worldwide, increasing morbidity and mortality due to antibiotic-resistant microbial infections has been observed. Therefore, better prevention and control of infectious diseases, as well as appropriate use of approved antibacterial drugs are crucial. There is also an urgent need for the continuous development and supply of novel antibiotics. Thus, identifying new antibiotics and their further development is once again a priority of natural product research. The antibiotic corallopyronin A was discovered in the 1980s in the culture broth of the Myxobacterium Corallococcus coralloides and serves, in the context of this review, as a show case for the development of a naturally occurring antibiotic compound. The review demonstrates how a hard to obtain, barely water soluble and unstable compound such as corallopyronin A can be developed making use of sophisticated production and formulation approaches. Corallopyronin A is a bacterial DNA-dependent RNA polymerase inhibitor with a new target site and one of the few representatives of this class currently in preclinical development. Efficacy against Gram-positive and Gram-negative pathogens, e.g., Chlamydia trachomatis, Orientia tsutsugamushi, Staphylococcus aureus, and Wolbachia has been demonstrated. Due to its highly effective in vivo depletion of Wolbachia, which are essential endobacteria of most filarial nematode species, and its robust macrofilaricidal efficacy, corallopyronin A was selected as a preclinical candidate for the treatment of human filarial infections. This review highlights the discovery and production optimization approaches for corallopyronin A, as well as, recent preclinical efficacy results demonstrating a robust macrofilaricidal effect of the anti-Wolbachia candidate, and the solid formulation strategy which enhances the stability as well as the bioavailability of corallopyronin A.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Krome, Anna K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Becker, Tim UNSPECIFIED UNSPECIFIED UNSPECIFIED Kehraus, Stefan UNSPECIFIED UNSPECIFIED UNSPECIFIED Schiefer, Andrea UNSPECIFIED UNSPECIFIED UNSPECIFIED Gutschow, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Chaverra-Munoz, Lillibeth UNSPECIFIED orcid.org/0000-0001-9624-7339 UNSPECIFIED Huttel, Stephan UNSPECIFIED UNSPECIFIED UNSPECIFIED Jansen, Rolf UNSPECIFIED UNSPECIFIED UNSPECIFIED Stadler, Marc UNSPECIFIED orcid.org/0000-0002-7284-8671 UNSPECIFIED Ehrens, Alexandra UNSPECIFIED orcid.org/0000-0002-2570-4034 UNSPECIFIED Pogorevc, Domen UNSPECIFIED UNSPECIFIED UNSPECIFIED Muller, Rolf UNSPECIFIED UNSPECIFIED UNSPECIFIED Hubner, Marc P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hesterkamp, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Pfarr, Kenneth UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoerauf, Achim UNSPECIFIED UNSPECIFIED UNSPECIFIED Wagner, Karl G. UNSPECIFIED orcid.org/0000-0003-2864-7191 UNSPECIFIED Konig, Gabriele M. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-681768
DOI:	10.1039/d2np00012a
Journal or Publication Title:	Nat. Prod. Rep.
Volume:	39
Number:	9
Page Range:	S. 1705 - 1721
Date:	2022
Publisher:	ROYAL SOC CHEMISTRY
Place of Publication:	CAMBRIDGE
ISSN:	1460-4752
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language BACTERIAL RNA-SYNTHESIS; MACROFILARICIDAL ACTIVITY; WOLBACHIA ENDOBACTERIA; MOLECULAR MOBILITY; PYRONE ANTIBIOTICS; GLIDING BACTERIA; DOXYCYCLINE; MYXOPYRONIN; INHIBITORS; ONCHOCERCIASIS Multiple languages Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/68176