c. difficile

Ridinilazole (SMT19969) is a novel narrow-spectrum nonabsorbable antibiotic. Ridinilazole showed potent inhibition of C. difficile (MIC90=0.125 mg/L) and was markedly more active than either metronidazole (MIC90 = 8 mg/L) or vancomycin (MIC90 = 2 mg/L).

Penicillin V Potassium (Phenoxymethylpenicillin potassium salt) is an orally administered, broad-spectrum penicillin antibiotic used for treating mild to moderate infections caused by susceptible gram-positive organisms.

Ibezapolstat (ACX-362E) is an orally active DNA polymerase IIIC inhibitor, an antibiotic with antibacterial activity that inhibits Clostridioides difficile (C. difficile) and can be used for studying Clostridioides difficile infections.

MGB-BP-3 is a synthetic antibiotic with bactericidal activity that inhibits bacterial DNA replication and can be used to study recurrent C. difficile infections.

SCUT1-2 is a bifunctional antibacterial agent with good oral bioavailability in mice (F=56.8%). It effectively kills the vegetative cells of C. difficile with a MIC of 0.06-0.50 μg/mL and inhibits spore germination in vitro. SCUT1-2 alleviates weight loss and diarrhea symptoms caused by C. difficile infection (CDI) in mice and prevents recurrence.

Cholic acid anilide is a synthetic bile acid and derivative of cholic acid that inhibits the germination of C. difficile strain R20291 spores in vitro (IC50 = 1.8 μM).1 |1. Sharma, S.K., Yip, C., Esposito, E.X., et al. The design, synthesis, and characterizations of spore germination inhibitors effective against an epidemic strain of Clostridium difficile. J. Med. Chem. 61(15), 6759-6778 (2018).

Isodeoxycholic Acid is a bile acid that is formed via epimerization of deoxycholic acid by intestinal bacteria. It has a greater critical micelle concentration than DCA, indicating reduced detergent activity, and is less active than DCA in inhibiting growth in a panel of seven gut commensal bacteria species. Isodeoxycholic Acid(0.1%) inhibits spore germination induced by taurocholic acid in several C. difficile strains, as well as decreases the cytotoxicity of C. difficile culture supernatants to Vero cells. Plasma levels of isodeoxycholic acid are decreased in a rat model of high-fat diet-induced obesity compared with rats fed a normal diet.

ATPase-IN-2 is a compound that acts as an inhibitor of ATPase, with an IC50 value of 0.9 μM. It also inhibits the glycohydrolase activity of C. difficile toxin B (TcdB) with an AC50 value of 30.91 μM. ATPase-IN-2 is commonly utilized in ATP-related research [1].

Cefminox (Sodium) is a new cephamycin antibiotic possessing a D-amino acid moiety derived from D-cysteine at the C-7B side chain. Cefminox is active against a wide range of bacteria, especially Gram-negative and anaerobic bacteria. Cefminox shows excellent in vivo efficacy (ED50) which is higher than would be expected from its in vitro activity (MIC). Moreover, cefminox possesses more potent activity in suppression of bacterial regrowth than other cephems[1]. Cefminox (Sodium) was the most active beta-lactam, with an MIC at which 50% of isolates are inhibited (MIC50) of 1.0 microg ml and an MIC90 of 16.0 microg ml. Cefminox was especially active against Bacteroides fragilis (MIC90, 2.0 microg ml), Bacteroides thetaiotaomicron (MIC90, 4.0 microg ml), fusobacteria (MIC90, 1.0 microg ml), peptostreptococci (MIC90, 2.0 microg ml), and clostridia, including Clostridium difficile (MIC90, 2.0 microg ml)[2]. The use of a single preoperative dose of cefminox was similar in efficacy to 3 doses of cefoxitin administered every 4 hours, and that the serum and tissue concentrations attained provide adequate antibiotic coverage[3]. Moreover, cefminox as a dual agonist of IP (Prostacyclin receptor) and PPARγ (peroxisome proliferator-activated receptor-gamma) that significantly inhibits PASMC proliferation by up-regulation of PTEN (phosphatase and tensin homolog) and cAMP ( cyclic adenosine monophosphate), suggesting that it has potential for treatment of PAH(pulmonary arterial hypertension)[4].

Benastatin B is a polyketide synthase-derived benastatin that has been found in Streptomyces and has diverse biological activities. It inhibits glutathione S-transferase (GST; Ki = 3.7 µM for the rat liver enzyme).2 Benastatin B also inhibits the transglycosylase activity of A. baumannii, C. difficile, E. coli, and S. aureus recombinant penicillin-binding proteins (PBPs; IC50s = 16, 53.3, 30.7, and 31.6 µM, respectively).3 It is active against several bacteria, including methicillin-resistant S. aureus (MRSA; MIC = 3.12 µg ml).

Bezlotoxumab, a human monoclonal antibody, targets and binds to Clostridium difficile (C. difficile) toxin B, thereby inhibiting its ability to damage intestinal epithelium and cause colitis [1].

Actoxumab is a humanized monoclonal antibody targeting Clostridium difficile toxin A (TcdA), preventing the binding of TcdA to target cells and neutralizing toxin activity by inhibiting the first step of TcdA.

Antibacterial Agent 156 (Compound 57), a bactericidal that selectively targets C. difficile cell-wall synthesis, demonstrates potent activity with minimal inhibitory concentrations of 0.5 μg mL for MIMIC50 (101 strains) and 1 μg mL for MIC90 (101 strains) [1].

Compound 6d (Antibacterial agent 159) is an antibiotic effective against impetigo and Clostridium difficile infection (CDI), with no observed recurrence for CDI and minimal impact on the beneficial gut microbiome [1].

Scandoside, a cyclic enolide that can be isolated from Haemophilus difficile, exhibits anti-inflammatory activity, inhibits the expression levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), TNF-α, and IL-6 messenger RNA (mRNA), and inhibits the nuclear transcription factor, kappa-B alpaha (IκB-α), p38, extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) inhibitor phosphorylation.

D-CopA3 is an inhibitor of MDM2 and an activator of the p53 signaling pathway. It exhibits cytotoxicity in colorectal cancer cells HCT-116, LoVo, and RKO with IC50 values of 15-18 μM and induces JNK Beclin-1 mediated autophagy. D-CopA3 downregulates the expression of the cell cycle inhibitor protein p21Cip1 Waf1, enhances mucosal barrier function, and reduces infiltration of inflammatory mediators. It shows anti-inflammatory properties in mouse models of acute enteritis induced by C. difficile toxin A and chronic colitis induced by DSS. Additionally, D-CopA3 demonstrates antitumor activity in a mouse HCT-116 xenograft model.