Bis-Cyclic Guanidines as a Novel Class of Compounds Potent against Clostridium difficile

ChemMedChem
Chunhui LiJianfeng Cai

Abstract

Clostridium difficile infection (CDI) symptoms range from diarrhea to severe toxic megacolon and even death. Due to its rapid acquisition of resistance, C. difficile is listed as an urgent antibiotic-resistant threat, and has surpassed methicillin-resistant Staphylococcus aureus (MRSA) as the most common hospital-acquired infection in the USA. To combat this pathogen, a new structural class of pseudo-peptides that exhibit antimicrobial activities could play an important role. Herein we report a set of bis-cyclic guanidine compounds that show potent antibacterial activity against C. difficile with decent selectivity. Eight compounds showed high in vitro potency against C. difficile UK6 with MIC values of 1.0 μg mL-1 , and cytotoxic selectivity index (SI) values up to 37. Moreover, the most selective compound is also effective in the treatment of C. difficile-induced disease in a mouse model of CDI, and appears to be a very promising new candidate for the treatment of CDI.

References

Feb 1, 2002·The New England Journal of Medicine·John G Bartlett
May 13, 2005·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Jacques PepinClaude Bourassa
Jan 5, 2008·Nature Clinical Practice. Gastroenterology & Hepatology·Lynne V McFarland
Feb 7, 2008·Emerging Infectious Diseases·Matthew D RedelingsLaurene Mascola
May 15, 2008·British Journal of Biomedical Science·J S Brazier
Oct 29, 2008·Antimicrobial Agents and Chemotherapy·Kaori TanakaKunitomo Watanabe
May 22, 2009·Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases·M GrareR E Duval
Mar 24, 2010·Infection Control and Hospital Epidemiology : the Official Journal of the Society of Hospital Epidemiologists of America·Stuart H CohenUNKNOWN Infectious Diseases Society of America
Jun 5, 2010·Expert Opinion on Investigational Drugs·Hoonmo L KooHerbert L Dupont
Feb 15, 2013·Journal of the American Chemical Society·Thomas BöttcherJon Clardy
Nov 19, 2013·Current Topics in Medicinal Chemistry·Lissa S TsutsumiDianqing Sun
Feb 18, 2014·Cell·Laura HobleyAnthony J Michael
Aug 26, 2014·Chembiochem : a European Journal of Chemical Biology·Megan C JenningsWilliam M Wuest
Jan 7, 2015·Nature·Losee L LingKim Lewis
Feb 26, 2015·The New England Journal of Medicine·Fernanda C LessaL Clifford McDonald
Apr 29, 2015·Pediatric Hematology and Oncology·Chittalsinh M RauljiLolie C Yu
Oct 27, 2015·Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics·Regis P KowalskiFrancis S Mah
Sep 28, 2017·Chemical Reviews·Sean E RossiterWilliam M Wuest
Oct 21, 2017·Chemical Communications : Chem Comm·Peng TengJianfeng Cai
Apr 28, 2018·Chemical Communications : Chem Comm·Mohini M KonaiJayanta Haldar

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Citations

Jul 1, 2020·Frontiers in Chemistry·Minghui WangJianfeng Cai
Mar 1, 2021·European Journal of Medicinal Chemistry·Seong-Heun KimDaniele Castagnolo
Jan 17, 2020·ACS Applied Materials & Interfaces·Mi ZhouJianfeng Cai
Sep 12, 2020·Journal of Medicinal Chemistry·Minghui WangJianfeng Cai

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