Limits...
Progress in the discovery of treatments for C. difficile infection: A clinical and medicinal chemistry review.

Tsutsumi LS, Owusu YB, Hurdle JG, Sun D - Curr Top Med Chem (2014)

Bottom Line: Clostridium difficile is an anaerobic, Gram-positive pathogen that causes C. difficile infection, which results in significant morbidity and mortality.Antibiotics are divided into natural product inspired and synthetic small molecule compounds that may have the potential to be more efficacious than currently approved treatments.This includes potency, selectivity, reduced cytotoxicity, and novel modes of action to prevent resistance.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Sciences, The Daniel K. Inouye College of Pharmacy, University of Hawai'i at Hilo, 34 Rainbow Drive, Hilo, HI 96720, USA. dianqing@hawaii.edu.

ABSTRACT
Clostridium difficile is an anaerobic, Gram-positive pathogen that causes C. difficile infection, which results in significant morbidity and mortality. The incidence of C. difficile infection in developed countries has become increasingly high due to the emergence of newer epidemic strains, a growing elderly population, extensive use of broad spectrum antibiotics, and limited therapies for this diarrheal disease. Because treatment options currently available for C. difficile infection have some drawbacks, including cost, promotion of resistance, and selectivity problems, new agents are urgently needed to address these challenges. This review article focuses on two parts: the first part summarizes current clinical treatment strategies and agents under clinical development for C. difficile infection; the second part reviews newly reported anti-difficile agents that have been evaluated or reevaluated in the last five years and are in the early stages of drug discovery and development. Antibiotics are divided into natural product inspired and synthetic small molecule compounds that may have the potential to be more efficacious than currently approved treatments. This includes potency, selectivity, reduced cytotoxicity, and novel modes of action to prevent resistance.

Show MeSH

Related in: MedlinePlus

Chemical structures of natural product inspired antibiotics with anti-difficile activity.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3921470&req=5

Figure 3: Chemical structures of natural product inspired antibiotics with anti-difficile activity.

Mentions: These antibiotics are of natural origin, e.g., from bacterial sources or plant extracts. Although bacteria and fungi are currently the leading sources of antimicrobials, plants and extracts from plant materials have been used in traditional medicine worldwide and represent an underexploited resource for novel antibacterial therapeutics [178]. These naturally occurring compounds are often part of the plant defense towards attacks by pathogens. Commonly, these compounds are classified as phytoalexins, while other products termed phytoanticipins are inactive [179]. Some common classes of phytochemicals include flavonoids, alkaloids, lactones, and polyphenols which have been reported to show antibacterial activity [178, 180-183]. Due to the rising number of studies that showed activity of plants and their extracts, and the history of efficacy of traditional medicine, these sources may be able to provide a new generation of anti-difficile agents [181]. The antibiotics in Fig. 3 include natural products and natural product analogs with improved anti-difficile activity and/or more desirable physicochemical properties.


Progress in the discovery of treatments for C. difficile infection: A clinical and medicinal chemistry review.

Tsutsumi LS, Owusu YB, Hurdle JG, Sun D - Curr Top Med Chem (2014)

Chemical structures of natural product inspired antibiotics with anti-difficile activity.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3921470&req=5

Figure 3: Chemical structures of natural product inspired antibiotics with anti-difficile activity.
Mentions: These antibiotics are of natural origin, e.g., from bacterial sources or plant extracts. Although bacteria and fungi are currently the leading sources of antimicrobials, plants and extracts from plant materials have been used in traditional medicine worldwide and represent an underexploited resource for novel antibacterial therapeutics [178]. These naturally occurring compounds are often part of the plant defense towards attacks by pathogens. Commonly, these compounds are classified as phytoalexins, while other products termed phytoanticipins are inactive [179]. Some common classes of phytochemicals include flavonoids, alkaloids, lactones, and polyphenols which have been reported to show antibacterial activity [178, 180-183]. Due to the rising number of studies that showed activity of plants and their extracts, and the history of efficacy of traditional medicine, these sources may be able to provide a new generation of anti-difficile agents [181]. The antibiotics in Fig. 3 include natural products and natural product analogs with improved anti-difficile activity and/or more desirable physicochemical properties.

Bottom Line: Clostridium difficile is an anaerobic, Gram-positive pathogen that causes C. difficile infection, which results in significant morbidity and mortality.Antibiotics are divided into natural product inspired and synthetic small molecule compounds that may have the potential to be more efficacious than currently approved treatments.This includes potency, selectivity, reduced cytotoxicity, and novel modes of action to prevent resistance.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Sciences, The Daniel K. Inouye College of Pharmacy, University of Hawai'i at Hilo, 34 Rainbow Drive, Hilo, HI 96720, USA. dianqing@hawaii.edu.

ABSTRACT
Clostridium difficile is an anaerobic, Gram-positive pathogen that causes C. difficile infection, which results in significant morbidity and mortality. The incidence of C. difficile infection in developed countries has become increasingly high due to the emergence of newer epidemic strains, a growing elderly population, extensive use of broad spectrum antibiotics, and limited therapies for this diarrheal disease. Because treatment options currently available for C. difficile infection have some drawbacks, including cost, promotion of resistance, and selectivity problems, new agents are urgently needed to address these challenges. This review article focuses on two parts: the first part summarizes current clinical treatment strategies and agents under clinical development for C. difficile infection; the second part reviews newly reported anti-difficile agents that have been evaluated or reevaluated in the last five years and are in the early stages of drug discovery and development. Antibiotics are divided into natural product inspired and synthetic small molecule compounds that may have the potential to be more efficacious than currently approved treatments. This includes potency, selectivity, reduced cytotoxicity, and novel modes of action to prevent resistance.

Show MeSH
Related in: MedlinePlus