Corticosteroids structure-activity relationships

Robert, D, Amat, L. and Carb6-Dorca, R. (1999). Three-Dimensional Quantitative Structure-Activity Relationships from Timed Molecular Quantum Similarity Measures Prediction of the Corticosteroid-Binding Globulin Binding Affinity for a Steroid Family. J.Chem.Inf.Comput.Sci., 39, 333-344. [R]... 

Robert D, Amat L, Carbo-Dorca R. Three-dimensional quantitative structure-activity relationships from tuned molecular quantum similarity measures prediction of the corticosteroid-binding globulin binding affinity for a steroid family. J Chem Inf Comput Sci 1999 39 333-344. 

Green MJ, Berkenkopf J, Fernandez X, et al. Synthesis and structure-activity relationships in a novel series of topically active corticosteroids. J Steroid Biochem 1979 11 61-66. 

Popper TL, Gentles MJ, Kung TT, et al. Structure-activity relationships of a series of novel topical corticosteroids. J Steroid Biochem 1987 27 837-843. 

Structure-Activity Relationships of Corticosteroid Cross-Reactions... 

Table I contains a list of drugs with confirmed activity of PGS ase inhibitors. Shen and GryglewskiH have independently proposed structure activity relationships to account for the inhibitory action of most, if not all, of the compounds mentioned in Table I. Other structures reported as PGS ase inhibitors are corticosteroids,some psychotropic drugs,antiestrogens,fatty acid hydroperoxides,1 3 and various acetylenic fatty acids.

PhiUipps GH, Bailey EJ, Bain BM, BoreUa RA, Buckton JB, Clark JC, Doherty AE, English AF, Fazakerley H. Synthesis and structure-activity relationships in a series of antiinflammatory corticosteroid analogs, halomethyl androstane 17p-carhothioates and-7p-carhoselenoates. J. Med. Chem. 1994 37 3717-3729. 

Although structure-function relationships of G-6-Pase are of interest in themselves, it is important to point out that the alterations of activity seen in vitro as a result of treatment with phospholipases have functional counterparts in vivo. Already mentioned above is the Kq-s-p change in fasted or alloxan-diabetic animals (Segal and Washko, 1959 Nordlie et al., 1968). In some settings it is also possible to show that apparent increases in the activity of G-6-Pase at Vmax are not due to the synthesis of new enzyme. In rats treated with the corticosteroid triamcinolone, for example, G-6-Pase activity increases, but this increase is not inhibited by prior administration of actinomycin D (Arion and Nordlie, 1967). On the other hand, whereas in vitro treatment of micro-somes with deoxycholate increases the activity of G-6-Pase in micro-somes from control animals by about 50 percent, the increase on deoxycholate treatment of microsomes from animals treated with acti-... 

A monograph concerned with the configurations and conformations of corticosteroids provides detailed information particularly on mass spectra and and n.m.r., and discusses side-chain conformations of corticosteroids both with and without C-18 oxygen functions the relationships between biological activity and conformation are discussed. The structural features and conformations compatible with anaesthetic activity in pregnane derivatives have also been reviewed. ... 

In connection with the work on the relationship between chemical structure and anti-inflammatory activity, the effect of ursolic acid, betulin, betulinic acid and erythrodiol on a system of chronic dermal edema and cellular proliferation caused by repeated administration of TPA has recently been examined [89], This experimental model of chronic inflammation has considerable selectivity for corticosteroids and leukotriene synthesis inhibitors. Erythrodiol and ursolic acid were significantly effective and also reduced the neutrophil infiltration detected by MPO activity. The lupane derivatives, betulin and betulinic acid, despite their possible steroid-like mechanism of action [47], were not effective in the chronic model. This result could mean that a six-member E ring of the pentacyclic structure is necessary for the activity against a multiple dose of TPA. The data confirm that a hydroxyl group at the C-28 position is important for the activity, as is also true in the case of erythrodiol, and it may explain the anti-inflammatory effect of this compound in each of the methods. 

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