Comparative analysis of mutagenic potency of 1-nitro-acridine derivatives

Antitumor 1-nitroacridine derivative C-1748, induces apoptosis, necrosis or senescence in human colon carcinoma HCT8 and HT29 cells

“…1), was found to have significant cytotoxic activity in vitro towards cancer cell lines and high antitumor activity against several prostate (LnCaP, JCA, PC3, TSU) and colon carcinoma (HCT8) xenografts in nude mice [6]. Pre-clinical toxicology studies in rodent and dogs showed C-1748 to have very low systemic toxicity along with a lowered mutagenic potential [7,8,9]. C-1748, as well as Ledakrin and other 1-nitroacridines, after metabolic activation bind covalently to DNA [10] and induced DNA crosslinking in tumor cells, which was crucial for biological activity of these compounds [11,12,13].…”

Pre-clinical evaluation of 1-nitroacridine derived chemotherapeutic agent that has preferential cytotoxic activity towards prostate cancer

“…17 Among several chemotherapeutic regimens being explored are docetaxel, in phase II trials, with response rates between 20-40%; 8,[18][19][20] estramustine plus taxane in phase III Southwest Oncology Group (SWOG) trial with objective responses in less than 20% of patients; 8,20,21 ketoconazole in Eastern Cooperative Oncology Group (ECOG)-sponsored phase III trial 8,[22][23][24] and carboplatin in phase II trials, showed significant prostate specific antigen (PSA) reductions, while less than 10% of patients exhibited a complete response. 25 Only a subpopulation of patients benefit from chemotherapy and since none of the agents are specific for CaP alongwith unacceptable toxicity profiles [30][31][32][33][34][35][36][37][38] makes it imperative to search for alternative chemotherapeutic agents.…”

“…Our pre-clinical toxicology studies in rodents 33 and dogs 34 showed C-1748 to have very low systemic toxicity along with a lowered mutagenic potential. 35 The 4-methyl-1-nitroacridines retain the differential cytotoxic capacity of ledakrin, while demonstrating a striking specificity for CaP and lowered systemic toxicities. 36 The present study uses cell culture models and human cancer cell xenografts to demonstrate that C-1748 has specific anti-cancer activity towards CaP and excellent host tolerance with potential for further clinical development as a chemotherapeutic drug for CaP.…”

New 9-Aminoacridine Derivative: Synthesis, Study and Potential Application as pH Indicator in Organic Solvents

“…4 The anticancer effect of nitro-9-aminoacridine derivatives is reported in the literature. 5,6 The 9-AA is also described to be a suitable matrix for the matrix assisted laser desorption/ionization (MALDI) and can even be used as indicator of transmembrane pH difference.7-9 A pH indicator highlights changes in the hydrogenionic potential and can be used to determine chemical processes involving acids and bases. More complex methods of quantifying acidity require expensive instrumentation, what makes the usage of pH indicators still important.…”

“…4 The anticancer effect of nitro-9-aminoacridine derivatives is reported in the literature. 5,6 The 9-AA is also described to be a suitable matrix for the matrix assisted laser desorption/ionization (MALDI) and can even be used as indicator of transmembrane pH difference.…”