The activity of eight topoisomerase inhibitors was investigated against five clinical isolates of Pneumocystis carinii. Susceptibility tests were performed by inoculation of the organisms on to a cell monolayer and parasites were counted after 72 h incubation at 37 degrees C. Culture plates were added with Dulbecco's modified Eagle's medium containing serial dilutions of lomefloxacin, norfloxacin, ofloxacin, pefloxacin, rufloxacin, camptothecin, amsacrine and etoposide. Atovaquone, pentamide isethionate and co-trimoxazole were used as control drugs. Etoposide gave inhibition comparable to that observed with atovaquone. Poor activity was demonstrated by pefloxacin, while the other topoisomerase inhibitors had no significant effect.
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http://dx.doi.org/10.1093/jac/40.4.583 | DOI Listing |
Pharmaceuticals (Basel)
January 2025
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Sohag University, Sohag 82524, Egypt.
Ciprofloxacin, a widely used second-generation fluoroquinolone for treating bacterial infections, has recently shown notable anticancer properties. This review explores progress in developing ciprofloxacin derivatives with anticancer properties, emphasizing key structural changes that improve their therapeutic effectiveness by modifying the basic group at position 7, the carboxylic acid group at position 3, or both. It further investigates the mechanisms by which these derivatives fight cancer, such as inducing apoptosis, arresting the cell cycle, inhibiting topoisomerase I and II, preventing tubulin polymerization, suppressing interleukin 6, blocking thymidine phosphorylase, inhibiting multidrug resistance proteins, and hindering angiogenesis.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Department of Pharmacy, College of Pharmacy, Research Institute for Drug Development, Pusan National University, Busan 46241, Republic of Korea.
Topoisomerase II inhibitors, particularly etoposide, have long been integral to the treatment of lung cancer, especially small cell lung cancer. This review comprehensively examines the mechanisms of action of etoposide, its clinical efficacy, and its role in current lung cancer treatment regimens. Etoposide exerts its anticancer effects by inducing DNA strand breaks through the inhibition of topoisomerase II, leading to cancer cell apoptosis.
View Article and Find Full Text PDFCancers (Basel)
January 2025
Eli Lilly and Company, Indianapolis, IN 46221, USA.
Small-cell lung cancer (SCLC) is a recalcitrant form of cancer, representing 15% of lung cancer cases globally. SCLC is classified within the range of neuroendocrine pulmonary neoplasms, exhibiting shared morphologic, ultrastructural, immunohistochemical, and molecular genomic features. It is marked by rapid proliferation, a propensity for early metastasis, and an overall poor prognosis.
View Article and Find Full Text PDFDrugs
January 2025
Department of Chemical Biology, Helmholtz Centre for Infection Research, Inhoffenstraße 7, 38124, Braunschweig, Germany.
The rise of antimicrobial resistance represents a significant global health threat, driven by the diminishing efficacy of existing antibiotics, a lack of novel antibacterials entering the market, and an over- or misuse of existing antibiotics, which accelerates the evolution of resistant bacterial strains. This review focuses on innovative therapies by highlighting 19 novel antibacterials in clinical development as of June 2024. These selected compounds are characterized by new chemical scaffolds, novel molecular targets, and/or unique mechanisms of action, which render their potential to break antimicrobial resistance particularly high.
View Article and Find Full Text PDFJ Med Chem
January 2025
Department of Respiratory and Critical Care Medicine, Molecularly Targeted Research and Development Laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China.
To overcome the compensatory effect between Topo I and II, one of the reasons accounting for the resistance of SCLC patients, we are pioneering the use of 3-arylisoquinolines to develop dual inhibitors of Topo I/II for the management of SCLC. A total of 46 new compounds were synthesized. Compounds (IC = 1.
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