A new class of prophylactic metallo-antibiotic possessing potent anti-cancer and anti-microbial properties
Year: 2019
Type: article
Abstract: . Biophysical studies involving calf thymus DNA indicate the complexes intercalate or semi-intercalate DNA via the minor groove. All complexes exhibited excellent nuclease activity with DNA strand scission being mediated predominantly via superoxide and hydroxyl radicals. The complexes were found to have promising anti-proliferative effects against a human breast adenocarcinoma cell line (MCF-7) and a human prostate carcinoma cell line (DU145) with low micromolar and, in some cases, nanomolar cytotoxicities observed. Selective targeting of Gram positive bacteria was also identified by this complex class with one lead compound having an order of magnitude greater potency against Methicillin-resistant S. aureus (MRSA) as compared to the CipA ligand. Importantly, from a clinical stand point, these complexes were also found to be well tolerated in an in vivo Galleria mellonella larvae model, which has both functional and structural similarities to that of the innate immune system of mammals.
Source: Dalton Transactions
DOI: 10.1039/c9dt00250b
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Awards: G1494226688, G2283509467, G3036383818, G3037763369, G3345895242, G4592723558, G4937468798, Polynuclear Platinum(II) Biomaterials (PPtBio) for Antisense Therapeutic Application and Detection of Human Genetic Disease, Click Chemistry for Future Gene Therapies to Benefit Citizens, Researchers and Industry, G6590639739, G7000258675, Exploiting Chromatin as a New Molecular Target for the Development of Novel Metallochemotherapeutics with Enhanced Selectivity and Activity Towards Cancer Cells, Breaking the cancer drug resistance paradigm: a novel prodrug strategy for multi-modal chemotherapeutics, Excellent Tallinn University of Technology Research Chair in Green Chemistry and Technology, G8512683158
OpenAlex ID: W2932278419