[Measurements and calculations on aglycon liberation from highly masked CMT selectines with beta-glucuronidase at pH 6. Realization of the principle of transport form-activity in anti-cancer drugs: theory of selectivity].
The authors describe methods and results on the aglycon liberation from several glucuronides using beta-flucuronidase in vitro. The glucuronides examined are prototypes of new potent anticancer drugs (so-called CMT selectines). Basing on the knowledge of the values and parameters involved theoretical considerations result in evaluation of the anticipated selective action of CMT selectines in artificially hyperacidified cancer tissues compared to normal tissues. The equations derived from certain mathematical simplifications are presented. The calculated high selectivity S approximately 20 can only be realized in vivo if the "masking index" s as to toxic action and renal clearance of a chosen CMT selectine is greater than 20. In fact, the hitherto known CMT selectines exhibit sufficiently high masking indices that the realization of a true transportation form/active form principle using different cancerotoxic agents as aglycones can be assumed.
D000970:Antineoplastic Agents / Q000378:metabolism*; D001692:Biological Transport; D005965:Glucuronates / Q000378:metabolism*; D005966:Glucuronidase; D006863:Hydrogen-Ion Concentration; D008433:Mathematics; D009369:Neoplasms / Q000188:drug therapy; D013329:Structure-Activity Relationship; D013995:Time
D000970:Antineoplastic Agents; D005965:Glucuronates; D005966:Glucuronidase
Messungen und Berechnungen zur Aglykon-Freisetzung aus hochmaskierten CMT-Selectinen mit beta-Glukuronidase bei pH 6 Realisierung des Transportform-Wirkform-Prinzips mit Kanzerotoxika: Selektivitätstheorie.