RESUMEN
Despite significant research in understanding of neoplastic diseases, the success rate for oncology drugs is relatively very low. A major challenge before the scientific community is to design new chemical entities that will be highly selective for cancer cells so as to minimize side effects. Classification models (CMs) models play a prominent role in prediction of the biological properties of newly designed compounds before their synthesis and prevent non-optimal use of resources. Though correlation models far outnumber classification models for development of various therapeutic agents but the significance of classification models for development of anti-cancer agents can not be underestimated. Various techniques employed for development of classification models for anti-cancer activity have been briefly reviewed. Moreover, successful use of some of these classification techniques for the development of models for anti-proliferative activity has been illustrated using a data set comprising of 53 analogues of N-Benzoylated phenoxazines and phenothiazines. Resulting classification models with high degree of accuracy can play a vital role in providing lead structures for the development of novel anti-proliferative agents for cancer chemotherapy.
Asunto(s)
Antineoplásicos/clasificación , Diseño Asistido por Computadora , Diseño de Fármacos , Oxazinas/clasificación , Fenotiazinas/clasificación , Antineoplásicos/química , Antineoplásicos/farmacología , Árboles de Decisión , Humanos , Concentración 50 Inhibidora , Células K562 , Neoplasias/tratamiento farmacológico , Oxazinas/química , Oxazinas/farmacología , Fenotiazinas/química , Fenotiazinas/farmacología , Análisis de Componente Principal , Relación Estructura-Actividad , Máquina de Vectores de SoporteRESUMEN
In the course of screening for inhibitors of osteoclastogenesis, a new substance designated as ICM0201 was isolated from a fermentation broth of Cunninghamella sp. F-1490. ICM0201 inhibited the formation of osteoclasts in mouse bone marrow cells with an IC50 value of 0.78 microg/ml and showed weak cytotoxicity against bone marrow cells.
Asunto(s)
Antibacterianos/clasificación , Cunninghamella/química , Compuestos Heterocíclicos con 3 Anillos/clasificación , Oxazinas/clasificación , Animales , Antibacterianos/biosíntesis , Antibacterianos/aislamiento & purificación , Antibacterianos/farmacología , Fermentación , Compuestos Heterocíclicos con 3 Anillos/aislamiento & purificación , Compuestos Heterocíclicos con 3 Anillos/metabolismo , Compuestos Heterocíclicos con 3 Anillos/farmacología , Masculino , Ratones , Ratones Endogámicos C57BL , Oxazinas/aislamiento & purificación , Oxazinas/metabolismo , Oxazinas/farmacología , Células Tumorales CultivadasRESUMEN
Benadrostin, a new inhibitor of poly(ADP-ribose) synthetase was discovered in the fermentation broth of Streptomyces flavovirens MH499-O'F1. It was purified by chromatography followed by solvent extraction and then isolated as colorless prisms. Benadrostin has the molecular formula of C8H5NO4. It was competitive with the substrate, and the inhibition constant (Ki) was 34 microM.
