Reducing Environmental Pollution by Antibiotics through Design for Environmental Degradation

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Reducing Environmental Pollution by Antibiotics through Design for Environmental Degradation. / Leder, Christoph; Suk, Morten; Lorenz, Stefanie et al.
In: ACS Sustainable Chemistry & Engineering, Vol. 9, No. 28, 19.07.2021, p. 9358–9368.

Research output: Journal contributionsJournal articlesResearchpeer-review

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Leder C, Suk M, Lorenz S, Rastogi T, Pfeifer C, Kietzmann M et al. Reducing Environmental Pollution by Antibiotics through Design for Environmental Degradation. ACS Sustainable Chemistry & Engineering. 2021 Jul 19;9(28):9358–9368. doi: 10.1021/acssuschemeng.1c02243

Bibtex

@article{981a769b984440d68574ee820efe907c,
title = "Reducing Environmental Pollution by Antibiotics through Design for Environmental Degradation",
abstract = "The spread of antibiotic-resistant pathogenic bacteria is an increasing health issue worldwide. A possible origin of antibiotic resistance could be the persistence of antibiotics in the aquatic environment. To tackle this problem, restricted control of application of antibiotics in human and veterinary medicine has been proposed. However, these measures do not prevent the spreadof antibiotic resistance but may delay the process, since antibiotics are still continuously emitted into the environment and many persist there. Derived from ciprofloxacin (CIP), CIP-Hemi, a fluoroquinolone with improved environmental properties, was developed following the benign by design approach and using insilico and in vitro methods. CIP-Hemi was designed to maintain its required metabolic stability (human liver microsomes, intestinal microsomes, blood plasma) and antibiotic activity (MIC in the μg mL−1 range) against the target while transforming into an inactive fragment (CIP-d-CP) and a degradable linker present under acidic conditions, e.g., after excretion or when released into theenvironment. Moreover, CIP-Hemi and CIP-d-CP showed weaker cytotoxic and mutagenic or genotoxic effects compared to the parent compound CIP and therefore underline the feasibility of CIP-Hemi as a viable antibiotic drug candidate, demonstrating benign by design as a promising approach.",
keywords = "Chemistry, Antibiotics, Benign by design, Fluoroquinolones, Sustainability Science, Sustainable pharmacy, Green chemistry",
author = "Christoph Leder and Morten Suk and Stefanie Lorenz and Tushar Rastogi and Christian Pfeifer and Manfred Kietzmann and Daniel Jonas and Marion Buck and Axel Pahl and Klaus K{\"u}mmerer",
note = "Financial support from the German Federal Environmental Foundation (Deutsche Bundesstiftung Umwelt; Sustainable Pharmacy 2, Project No. 30389) is gratefully acknowledged. The authors thank Steffi Hinz and Janin Westphal for their excellent technical assistance and Lisa Kessler for helpful technical advice on the algal assay. The authors also acknowledge Multicase Inc. and Leadscope Inc. for kindly providing CASE Ultra and Leadscope QSAR software, respectively. A part of the antimicrobial screening was performed by CO-ADD (The Community for Antimicrobial Drug Discovery), funded by the Wellcome Trust (U.K.) and The University of Queensland (Australia). The molecular structure representations and SMILES codes were generated with Marvin sketch 15.6.8.0 kindly provided by ChemAxon Ltd. (Budapest, Hungary). Publisher Copyright: {\textcopyright} 2021 The Authors. Published by American Chemical Society.",
year = "2021",
month = jul,
day = "19",
doi = "10.1021/acssuschemeng.1c02243",
language = "English",
volume = "9",
pages = "9358–9368",
journal = "ACS Sustainable Chemistry & Engineering",
issn = "2168-0485",
publisher = "American Chemical Society",
number = "28",

}

RIS

TY - JOUR

T1 - Reducing Environmental Pollution by Antibiotics through Design for Environmental Degradation

AU - Leder, Christoph

AU - Suk, Morten

AU - Lorenz, Stefanie

AU - Rastogi, Tushar

AU - Pfeifer, Christian

AU - Kietzmann, Manfred

AU - Jonas, Daniel

AU - Buck, Marion

AU - Pahl, Axel

AU - Kümmerer, Klaus

N1 - Financial support from the German Federal Environmental Foundation (Deutsche Bundesstiftung Umwelt; Sustainable Pharmacy 2, Project No. 30389) is gratefully acknowledged. The authors thank Steffi Hinz and Janin Westphal for their excellent technical assistance and Lisa Kessler for helpful technical advice on the algal assay. The authors also acknowledge Multicase Inc. and Leadscope Inc. for kindly providing CASE Ultra and Leadscope QSAR software, respectively. A part of the antimicrobial screening was performed by CO-ADD (The Community for Antimicrobial Drug Discovery), funded by the Wellcome Trust (U.K.) and The University of Queensland (Australia). The molecular structure representations and SMILES codes were generated with Marvin sketch 15.6.8.0 kindly provided by ChemAxon Ltd. (Budapest, Hungary). Publisher Copyright: © 2021 The Authors. Published by American Chemical Society.

PY - 2021/7/19

Y1 - 2021/7/19

N2 - The spread of antibiotic-resistant pathogenic bacteria is an increasing health issue worldwide. A possible origin of antibiotic resistance could be the persistence of antibiotics in the aquatic environment. To tackle this problem, restricted control of application of antibiotics in human and veterinary medicine has been proposed. However, these measures do not prevent the spreadof antibiotic resistance but may delay the process, since antibiotics are still continuously emitted into the environment and many persist there. Derived from ciprofloxacin (CIP), CIP-Hemi, a fluoroquinolone with improved environmental properties, was developed following the benign by design approach and using insilico and in vitro methods. CIP-Hemi was designed to maintain its required metabolic stability (human liver microsomes, intestinal microsomes, blood plasma) and antibiotic activity (MIC in the μg mL−1 range) against the target while transforming into an inactive fragment (CIP-d-CP) and a degradable linker present under acidic conditions, e.g., after excretion or when released into theenvironment. Moreover, CIP-Hemi and CIP-d-CP showed weaker cytotoxic and mutagenic or genotoxic effects compared to the parent compound CIP and therefore underline the feasibility of CIP-Hemi as a viable antibiotic drug candidate, demonstrating benign by design as a promising approach.

AB - The spread of antibiotic-resistant pathogenic bacteria is an increasing health issue worldwide. A possible origin of antibiotic resistance could be the persistence of antibiotics in the aquatic environment. To tackle this problem, restricted control of application of antibiotics in human and veterinary medicine has been proposed. However, these measures do not prevent the spreadof antibiotic resistance but may delay the process, since antibiotics are still continuously emitted into the environment and many persist there. Derived from ciprofloxacin (CIP), CIP-Hemi, a fluoroquinolone with improved environmental properties, was developed following the benign by design approach and using insilico and in vitro methods. CIP-Hemi was designed to maintain its required metabolic stability (human liver microsomes, intestinal microsomes, blood plasma) and antibiotic activity (MIC in the μg mL−1 range) against the target while transforming into an inactive fragment (CIP-d-CP) and a degradable linker present under acidic conditions, e.g., after excretion or when released into theenvironment. Moreover, CIP-Hemi and CIP-d-CP showed weaker cytotoxic and mutagenic or genotoxic effects compared to the parent compound CIP and therefore underline the feasibility of CIP-Hemi as a viable antibiotic drug candidate, demonstrating benign by design as a promising approach.

KW - Chemistry

KW - Antibiotics

KW - Benign by design

KW - Fluoroquinolones

KW - Sustainability Science

KW - Sustainable pharmacy

KW - Green chemistry

UR - http://www.scopus.com/inward/record.url?scp=85111067533&partnerID=8YFLogxK

U2 - 10.1021/acssuschemeng.1c02243

DO - 10.1021/acssuschemeng.1c02243

M3 - Journal articles

VL - 9

SP - 9358

EP - 9368

JO - ACS Sustainable Chemistry & Engineering

JF - ACS Sustainable Chemistry & Engineering

SN - 2168-0485

IS - 28

ER -