SCHEMBL19952957

Last updated
SCHEMBL19952957
SCHEMBL19952957 structure.png
Identifiers
  • 4-[3-(4-cyclopentyloxyphenyl)-1,2,4-oxadiazol-5-yl]phenol
PubChem CID
Chemical and physical data
Formula C19H18N2O3
Molar mass 322.364 g·mol−1
3D model (JSmol)
  • C1CCC(C1)OC2=CC=C(C=C2)C3=NOC(=N3)C4=CC=C(C=C4)O
  • InChI=1S/C19H18N2O3/c22-15-9-5-14(6-10-15)19-20-18(21-24-19)13-7-11-17(12-8-13)23-16-3-1-2-4-16/h5-12,16,22H,1-4H2
  • Key:LTWUHRPUKBTFBZ-UHFFFAOYSA-N

SCHEMBL19952957 is an oxadiazole based antibiotic, originally developed in 2014 as a potential treatment for infections with methicillin-resistant Staphylococcus aureus (MRSA) and other antibiotic resistant bacteria. Subsequently, it has been found to be useful against Clostridium difficile as it not only kills active bacteria, but also inhibits the germination of the dormant spores which can otherwise often lead to persistent infections that repeatedly recur upon cessation of antibiotic treatment. While it is still only being researched in animals at this stage, this dual action is a significant advance over existing antibiotics, and it is likely that drugs from this class may be developed as new medications for the treatment of antibiotic resistant infections in humans. [1] [2] [3] [4]

See also

Related Research Articles

<span class="mw-page-title-main">Antibiotic</span> Antimicrobial substance active against bacteria

An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention of such infections. They may either kill or inhibit the growth of bacteria. A limited number of antibiotics also possess antiprotozoal activity. Antibiotics are not effective against viruses such as the common cold or influenza; drugs which inhibit growth of viruses are termed antiviral drugs or antivirals rather than antibiotics. They are also not effective against fungi; drugs which inhibit growth of fungi are called antifungal drugs.

<span class="mw-page-title-main">Vancomycin</span> Antibiotic medication

Vancomycin is a glycopeptide antibiotic medication used to treat a number of bacterial infections. It is used intravenously as a treatment for complicated skin infections, bloodstream infections, endocarditis, bone and joint infections, and meningitis caused by methicillin-resistant Staphylococcus aureus. Blood levels may be measured to determine the correct dose. Vancomycin is also taken orally as a treatment for severe Clostridium difficile colitis. When taken orally it is poorly absorbed.

<i>Clostridium</i> Genus of Gram-positive bacteria, which includes several significant human pathogens

Clostridium is a genus of anaerobic, Gram-positive bacteria. Species of Clostridium inhabit soils and the intestinal tract of animals, including humans. This genus includes several significant human pathogens, including the causative agents of botulism and tetanus. It also formerly included an important cause of diarrhea, Clostridioides difficile, which was reclassified into the Clostridioides genus in 2016.

<i>Clostridioides difficile</i> infection Disease caused by C. difficile bacteria

Clostridioides difficile infection , also known as Clostridium difficile infection, is a symptomatic infection due to the spore-forming bacterium Clostridioides difficile. Symptoms include watery diarrhea, fever, nausea, and abdominal pain. It makes up about 20% of cases of antibiotic-associated diarrhea. Antibiotics can contribute to detrimental changes in gut microbiota; specifically, they decrease short-chain fatty acid absorption which results in osmotic, or watery, diarrhea. Complications may include pseudomembranous colitis, toxic megacolon, perforation of the colon, and sepsis.

<span class="mw-page-title-main">Clindamycin</span> Antibiotic

Clindamycin is an antibiotic medication used for the treatment of a number of bacterial infections, including osteomyelitis (bone) or joint infections, pelvic inflammatory disease, strep throat, pneumonia, acute otitis media, and endocarditis. It can also be used to treat acne, and some cases of methicillin-resistant Staphylococcus aureus (MRSA). In combination with quinine, it can be used to treat malaria. It is available by mouth, by injection into a vein, and as a cream or a gel to be applied to the skin or in the vagina.

An antimicrobial is an agent that kills microorganisms (microbicide) or stops their growth. Antimicrobial medicines can be grouped according to the microorganisms they act primarily against. For example, antibiotics are used against bacteria, and antifungals are used against fungi. They can also be classified according to their function. The use of antimicrobial medicines to treat infection is known as antimicrobial chemotherapy, while the use of antimicrobial medicines to prevent infection is known as antimicrobial prophylaxis.

<span class="mw-page-title-main">Glycopeptide antibiotic</span> Class of antibiotic drugs

Glycopeptide antibiotics are a class of drugs of microbial origin that are composed of glycosylated cyclic or polycyclic nonribosomal peptides. Significant glycopeptide antibiotics include the anti-infective antibiotics vancomycin, teicoplanin, telavancin, ramoplanin and decaplanin, corbomycin, complestatin and the antitumor antibiotic bleomycin. Vancomycin is used if infection with methicillin-resistant Staphylococcus aureus (MRSA) is suspected.

<span class="mw-page-title-main">Carbapenem</span> Class of highly effective antibiotic agents

Carbapenems are a class of very effective antibiotic agents most commonly used for the treatment of severe bacterial infections. This class of antibiotics is usually reserved for known or suspected multidrug-resistant (MDR) bacterial infections. Similar to penicillins and cephalosporins, carbapenems are members of the beta-lactam antibiotics drug class, which kill bacteria by binding to penicillin-binding proteins, thus inhibiting bacterial cell wall synthesis. However, these agents individually exhibit a broader spectrum of activity compared to most cephalosporins and penicillins. Furthermore, carbapenems are typically unaffected by emerging antibiotic resistance, even to other beta-lactams.

<span class="mw-page-title-main">Fecal microbiota transplant</span> Process of transplantation of fecal bacteria from a healthy individual into a recipient

Fecal microbiota transplant (FMT), also known as a stool transplant, is the process of transferring fecal bacteria and other microbes from a healthy individual into another individual. FMT is an effective treatment for Clostridioides difficile infection (CDI). For recurrent CDI, FMT is more effective than vancomycin alone, and may improve the outcome after the first index infection.

<span class="mw-page-title-main">Rifaximin</span> Antibiotic medication

Rifaximin, is a non-absorbable, broad spectrum antibiotic mainly used to treat travelers' diarrhea. It is based on the rifamycin antibiotics family. Since its approval in Italy in 1987, it has been licensed in over more than 30 countries for the treatment of a variety of gastrointestinal diseases like irritable bowel syndrome, and hepatic encephalopathy. It acts by inhibiting RNA synthesis in susceptible bacteria by binding to the RNA polymerase enzyme. This binding blocks translocation, which stops transcription. It is marketed under the brand name Xifaxan by Salix Pharmaceuticals.

Any cause that reduces or increases reproductive success in a portion of a population potentially exerts evolutionary pressure, selective pressure or selection pressure, driving natural selection. It is a quantitative description of the amount of change occurring in processes investigated by evolutionary biology, but the formal concept is often extended to other areas of research.

<i>Clostridium tetani</i> Common soil bacterium and the causative agent of tetanus

Clostridium tetani is a common soil bacterium and the causative agent of tetanus. Vegetative cells of Clostridium tetani are usually rod-shaped and up to 2.5 μm long, but they become enlarged and tennis racket- or drumstick-shaped when forming spores. C. tetani spores are extremely hardy and can be found globally in soil or in the gastrointestinal tract of animals. If inoculated into a wound, C. tetani can grow and produce a potent toxin, tetanospasmin, which interferes with motor neurons, causing tetanus. The toxin's action can be prevented with tetanus toxoid vaccines, which are often administered to children worldwide.

<span class="mw-page-title-main">Polypeptide antibiotic</span> Class of antibiotics

Polypeptide antibiotics are a chemically diverse class of anti-infective and antitumor antibiotics containing non-protein polypeptide chains. Examples of this class include actinomycin, bacitracin, colistin, and polymyxin B. Actinomycin-D has found use in cancer chemotherapy. Most other polypeptide antibiotics are too toxic for systemic administration, but can safely be administered topically to the skin as an antiseptic for shallow cuts and abrasions.

<span class="mw-page-title-main">Ramoplanin</span> Antibiotic chemical

Ramoplanin (INN) is a glycolipodepsipeptide antibiotic drug derived from strain ATCC 33076 of Actinoplanes. It is effective against Gram-positive bacteria.

<span class="mw-page-title-main">Fidaxomicin</span> Antibiotic

Fidaxomicin, sold under the brand name Dificid among others, is the first member of a class of narrow spectrum macrocyclic antibiotic drugs called tiacumicins. It is a fermentation product obtained from the actinomycete Dactylosporangium aurantiacum subspecies hamdenesis. Fidaxomicin is minimally absorbed into the bloodstream when taken orally, is bactericidal, and selectively eradicates pathogenic Clostridioides difficile with relatively little disruption to the multiple species of bacteria that make up the normal, healthy intestinal microbiota. The maintenance of normal physiological conditions in the colon may reduce the probability of recurrence of Clostridioides difficile infection.

Copper and its alloys are natural antimicrobial materials. Ancient civilizations exploited the antimicrobial properties of copper long before the concept of microbes became understood in the nineteenth century. In addition to several copper medicinal preparations, it was also observed centuries ago that water contained in copper vessels or transported in copper conveyance systems was of better quality than water contained or transported in other materials.

<span class="mw-page-title-main">Cadazolid</span> Chemical compound

Cadazolid is an experimental antibiotic of the oxazolidinone class made by Actelion Pharmaceuticals Ltd. which is effective against Clostridium difficile, a major cause of drug resistant diarrhea in the elderly. Current drug treatments for this infection involve orally delivered antibiotics, principally fidaxomicin, metronidazole and vancomycin; the last two drugs are the principal therapeutic agents in use, but fail in approximately 20 to 45% of the cases. The drug works by inhibiting synthesis of proteins in the bacteria, thus inhibiting the production of toxins and the formation of spores. Cadazolid progressed through to Phase III clinical trials, but in its financial results for Q1 2018, Idorsia mentions that Actelion informed them that "following completion of Phase 3 data analysis of cadazolid - it has decided to discontinue the development of the compound."

<i>Clostridioides difficile</i> Species of bacteria

Clostridioides difficile is a bacterium that is well known for causing serious diarrheal infections, and may also cause colon cancer. It is known also as C. difficile, or C. diff, and is a Gram-positive species of spore-forming bacteria. Clostridioides spp. are anaerobic, motile bacteria, ubiquitous in nature and especially prevalent in soil. Its vegetative cells are rod-shaped, pleomorphic, and occur in pairs or short chains. Under the microscope, they appear as long, irregular cells with a bulge at their terminal ends. Under Gram staining, C. difficile cells are Gram-positive and show optimum growth on blood agar at human body temperatures in the absence of oxygen. C. difficile is catalase- and superoxide dismutase-negative, and produces up to three types of toxins: enterotoxin A, cytotoxin B and Clostridioides difficile transferase (CDT). Under stress conditions, the bacteria produce spores that are able to tolerate extreme conditions that the active bacteria cannot tolerate.

References

  1. US 10662164,Chang M, Mobashery S, Spink E, Ding D, Testero S, Leemans E, Boudreau M,"Non-beta lactam antibiotics",issued 26 May 2020, assigned to University of Notre Dame.
  2. US 11168062,Chang M, Mobashery S, Ding D,"Compounds for the treatment of Clostridium difficile infection",issued 9 November 2021, assigned to University of Notre Dame.
  3. Janardhanan J, Kim C, Qian Y, Yang J, Meisel JE, Ding D, et al. (May 2023). "A dual-action antibiotic that kills Clostridioides difficile vegetative cells and inhibits spore germination". Proceedings of the National Academy of Sciences of the United States of America. 120 (20): e2304110120. Bibcode:2023PNAS..12004110J. doi: 10.1073/pnas.2304110120 . PMC   10193928 . PMID   37155891. S2CID   258565494.
  4. Yirka B (9 May 2023). "Dual-action antibiotic found that kills C. difficile, preventing reinfections". Medical Xpress.