Anti-inflammatory steroids, lysosomal stabilization and parachor.
Parachor is an additive constitutive property of a molecule and is related to the molar volume and the surface tension. The parachor of a steroid can be calculated from its constituent atoms and bonds. The parachor of a biologically active molecule is related to the ability of that molecule to permeate hydrophobic regions of cells, especially cellular membranes. An examination of the parachor values of a large number of steroids shows that these values are correlated with a number of different biological activities, from independent sources. The ability of steroids to release lysosomal enzymes from isolated lysosomes in vitro is inversely related to the parachor of the steroid. A similar relationship holds for the release of lysosomal beta-glucoronidase (EC 3.2.1.31) from isolated lysosomes of rat preputial gland following in vivo administration of steroids. The relative anti-inflammatory potencies of steroids by several assay methods are directly proportional to their parachors. The relative ability of corticosteroids to uncouple oxidative phosphorylation and to swell isolated mitochondria in vitro show a direct proportionality with the steroidal parachor. The percutaneous absorptions of steroids show good correlation with parachors, stratum corneum-water partition coefficients and amylcaproate-water partition coefficients; but not with hexadecane-water partition coefficients. The application of parachor as a structure-activity correlation parameter in drug design is likely to yield useful information. The advantages and limitations of the calculated parachor method are discussed.
D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents; D001681:Biological Assay; D004967:Estrogens / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology*; D005966:Glucuronidase / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008247:Lysosomes / Q000201:enzymology*; D008933:Mitochondrial Swelling / Q000187:drug effects; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010539:Permeability; D011374:Progesterone / Q000494:pharmacology*; D051381:Rats; D012867:Skin / Q000378:metabolism; D013329:Structure-Activity Relationship; D013500:Surface Tension
D000728:Androgens; D000893:Anti-Inflammatory Agents; D004967:Estrogens; D005938:Glucocorticoids; D011374:Progesterone; D005966:Glucuronidase