RESUMO
A series of lavendamycin analogues with two, three or four substituents at the C-6, C-7 N, C-2', C-3' and C-11' positions were synthesized via short and efficient methods and evaluated as potential NAD(P)H:quinone oxidoreductase (NQO1)-directed antitumor agents. The compounds were prepared through Pictet-Spengler condensation of the desired 2-formylquinoline-5,8-diones with the required tryptophans followed by further needed transformations. Metabolism and toxicity studies demonstrated that the best substrates for NQO1 were also the most selectively toxic to NQO1-rich tumor cells compared to NQO1-deficient tumor cells.
Assuntos
Antineoplásicos/síntese química , Estreptonigrina/análogos & derivados , Antineoplásicos/metabolismo , Antineoplásicos/toxicidade , Linhagem Celular Tumoral , Humanos , NAD(P)H Desidrogenase (Quinona)/química , NAD(P)H Desidrogenase (Quinona)/genética , NAD(P)H Desidrogenase (Quinona)/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Estreptonigrina/química , Estreptonigrina/metabolismo , Estreptonigrina/toxicidade , Relação Estrutura-AtividadeRESUMO
A new classification of melanocytic nevi is presented that may incorporate 1 of 3 anatomic patterns, 1 of 12 architectural patterns, and 1of 3 cellular patterns in the diagnosis. In this scheme, the patterns are easy to understand, logical, and the end result is an unambiguous descriptive diagnosis. A pattern diagnosis for melanocytic nevi allows for an understandable and reproducible interpretation by the physician. The nosology of a pattern diagnosis is familiar to physicians. It is common to have a variety of histopathologic patterns for a clinical condition alone or in combination and to be portrayed in the clinical diagnosis. There are countless examples in the literature, such as squamous cell carcinoma (superficial, spindle cell, atypical fibroxanthomatous, pseudovascular types) and basal cell carcinoma (superficial, nodular, pigmented, cystic, morpheaform, fibroepithelial types) to mention but a few. Our classification emphasizes the benignancy of the melanocytic nevus and makes it feasible for the physician to picture it. A pattern diagnosis thus results in a bona fide service to the patient resulting in less confusion, misinterpretation, or fear of malignancy, as well as unnecessary surgery.