Phenanthrenequinone antiretroviral agents

Compounds 3 and 5 are the first phenanthrenequinones to exhibit significant virucidal activity against the retrovirus equine infectious anemia virus. They differ from hypericin in that their virucidal activity is not light dependent.     

Pediatric pharmacology of antifungal agents

Pediatric age groups display important differences in host biology, predisposing conditions, epidemiology, and presentation of fungal infections relative to the adult population. Over the past decade, major advances have been made in the field of medical mycology. Most importantly, an array of new antifungal agents has entered the clinical arena. Although pediatric approval of several of these agents remains to be established, the pediatric development of antifungal agents is moving forward. Invasive fungal infections will remain important causes for morbidity and mortality in immunocompromised pediatric patients. Although the availability of new therapeutic options is an important advance, antifungal therapy has become increasingly complex, and a thorough understanding of the available antifungal armamentarium is essential for the successful management of individual patients.     

Cellular pharmacology of polynuclear platinum anti-cancer agents

Study of the cellular pharmacology of the dinuclear platinum complexes, BBR3005 ([?trans-PtCl(NH3)2?2H2N(CH2)6NH2]2+), BBR3171 ([?cis-PtCl(NH3)2?2H2N(CH2)6NH2]2+) and the trinuclear platinum complex, BBR3464 ([?trans-PtCl(NH3)2?2 mu-?trans-Pt(NH3)2(H2N(CH2)6NH2)2?]4+) was undertaken in wild type and cisplatin-resistant L1210 murine leukemia cell lines. All complexes are potent cytotoxic agents against the wild type cell line. Only BBR3464 shows enhanced activity against the cisplatin-resistant cell line following a brief exposure. This enhanced activity is attributable, in part, to preserved accumulation, which contrasts with diminished accumulation of cisplatin and both dinuclear platinum complexes. The cisplatin-resistant cell line is relatively tolerant of DNA adducts induced by both cisplatin and BBR3464, but BBR3464 is much less affected. All complexes induce DNA interstrand cross-links. Di/trinuclear complex-induced interstrand cross-linking peaks early, suggesting rapid genomic access and interaction. Subsequent decay suggests susceptibility to DNA repair mechanisms. Peak and area-under-the-curve values for interstrand cross-linking among the complexes correlate poorly with cytotoxic effects, especially in the cisplatin-resistant cell line. This suggests that all interstrand cross-linking adducts are not equal in their cytotoxic effect, or other, non-interstrand cross-linking adducts are significant. BBR3464 has been selected for clinical development largely on the basis of results from in vivo activity and toxicity studies. These results show BBR3464 to have unique properties in the context of acquired cisplatin-resistance that enhance its candidacy as a potential anticancer agent.