475266-28-5Relevant academic research and scientific papers
Photoactivated Colibactin Probes Induce Cellular DNA Damage
Moodie, Lindon W. K.,Hubert, Madlen,Zhou, Xin,Albers, Michael F.,Lundmark, Richard,Wanrooij, Sjoerd,Hedberg, Christian
supporting information, p. 1417 - 1421 (2019/01/04)
Colibactin is a small molecule produced by certain bacterial species of the human microbiota that harbour the pks genomic island. Pks+ bacteria induce a genotoxic phenotype in eukaryotic cells and have been linked with colorectal cancer progression. Colibactin is produced in a benign, prodrug form which, prior to export, is enzymatically matured by the producing bacteria to its active form. Although the complete structure of colibactin has not been determined, key structural features have been described including an electrophilic cyclopropane motif, which is believed to alkylate DNA. To investigate the influence of the putative “warhead” and the prodrug strategy on genotoxicity, a series of photolabile colibactin probes were prepared that upon irradiation induced a pks+ like phenotype in HeLa cells. Furthermore, results from DNA cross-linking and imaging studies of clickable analogues enforce the hypothesis that colibactin effects its genotoxicity by directly targeting DNA.
New anti-MRSA and anti-VRE carbapenems: Synthesis and structure-activity relationships of 1β-metyl-2-(thiazol-2-ylthio)carbapenems
Sunagawa, Makoto,Itoh, Masanori,Kubota, Kubota,Sasaki, Akira,Ueda, Yutaka,Angehrn, Peter,Bourson, Anne,Goetschi, Erwin,Hebeisen, Paul,Then, Rudolf L.
, p. 722 - 757 (2007/10/03)
Discovery of novel antimicrobial agents effective against infections caused by drug-resistant pathogens is an important objective. In order to find a new parenteral carbapenem antibiotic, which has potent antibacterial activity especially against methicillin-resistant staphylococci, vancomycin-resistant enterococci and penicillin-resistant Streptococcus pneumoniae, a series of 1β-methylcarbapenems with thiazol-2-ylthio groups at the C-2 position have been synthesized. Structure-activity relationships were investigated which led to SM-197436 (27), SM-232721 (44) and SM-232724 (41), being selected for further evaluation.
