STEROIDS CLIX

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Abstract
Thirty progesterone analogues were tested for inhibitory activity on radial growth of Curvularia lunata and Trichophyton mentagrophytes. 21,21-dimethoxy progesterone (DMP) and 21, 21-diethoxy progesterone were the most active compounds on C. lunata and DMP, progesterone, 19-norprogesterone and deoxycorticosterone were most inhibitory on T. mentagrophytes. DMP also inhibited Colletptricham coffeanum, Fusarium moniliforme, Fusarium sativum and Rhizoctonia solani. Gram-positive bacteria, including mycobacteria, were inhibited by concentrations of DMP ranging from 1 to 100 ug/ml- Nocardia asteroides and N. brasiliensis showed sensitivity to the steroid at concentrations from 5 to 50 [mu]g/ml. No antimicrobial effect was observed on gram-negative bacteria and yeasts. DMP was essentially bacteriostatic or fungistatic and its effects on radial growth of C. lunata were not modified by inactive steroids (cortisone, hydro-cortisone) or precursors (squalene). However, inhibition of mycelial synthesis in submerged cultures was reversed by squalene or deoxycorticosterone. The complexity of groups attached to C-21, the suppression of the double bond between C-4 and C-5, reduction of A4-3 keto function, introduction of a double bond at C-l, and halogenation were modifications which decreased fungistatic action of DMP. T. mentagrophytes was influenced to a lesser degree by modifications of the steroid molecule. Metabolic studies related to 11-B hydroxylation of Reichstein''s compound S by C. lunata demonstrated that DMP at the concentrations from 1-10 [mu]g/ml significantly inhibited the formation of hydrocortisone. The inhibitory steroid prevents both cellular synthesis and enzyme action. In contrast, DMP did not affect the steroid hydroxylating abilities of Cunninghamella bainieri or adrenal gland homogenates.