Reducing Environmental Pollution by Antibiotics through Design for Environmental Degradation

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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 spread
of 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 in
silico 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 the
environment. 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.
Original languageEnglish
JournalACS Sustainable Chemistry & Engineering
Issue number28
Pages (from-to)9358–9368
Number of pages11
Publication statusPublished - 19.07.2021

Bibliographical 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 kindly provided by ChemAxon Ltd. (Budapest, Hungary).

Publisher Copyright:
© 2021 The Authors. Published by American Chemical Society.