Potencies for PGE1, l-sirenin, PROG, and PROG analogs to elicit calcium influx in human sperm
| # | Steroid | Steroid Alone | + 30 µM Mibefradil | ||||||
|---|---|---|---|---|---|---|---|---|---|
| pEC50 | Emax, % | n | pEC50 | Emax, % | n | ||||
| Activator | 1 | PROG | 8.43 ± 0.21 | 111 | 7 | 8.22 ± 0.15 | 42 | 3 | |
| 2 | PGE1 | 8.40 ± 0.24 | 101 | 8 | 8.33 ± 0.43 | 22 | 5 | ||
| 3 | l-sirenin | 6.02 ± 0.26 | 102 | 3 | 5.48 ± 0.23 | 22 | 3 | ||
| A Ring or A–B Ring Fusion | 10 | 3α,5α-pregnanolone | 6.56 ± 0.21 | 85 | 5 | 6.40 ± 0.19 | 29 | 3 | |
| 11 | 3α,5β-pregnanolone | 6.26 ± 0.25 | 102 | 3 | 6.47 ± 0.22 | 33 | 3 | ||
| 12 | 3β,5α-pregnanolone | 7.16 ± 0.11 | 99 | 4 | 7.08 ± 0.31 | 38 | 4 | ||
| 13 | 3β,5β-pregnanolone | 6.89 ± 0.20 | 92 | 4 | 7.05 ± 0.23 | 37 | 4 | ||
| 14 | 5α-dihydroprogesterone | 6.99 ± 0.05 | 87 | 3 | 6.95 ± 0.12 | 34 | 3 | ||
| 15 | 5β-dihydroprogesterone | 6.87 ± 0.17 | 95 | 3 | 6.67 ± 0.35 | 20 | 3 | ||
| 16 | 5α,6α-epoxypregnan-3,20-dionea | 6.08 ± 0.37 | 83 | 3 | 5.96 ± 0.19 | 12 | 3 | ||
| 17 | 5β,6β-epoxypregnan-3,20-dionea | 6.38 ± 0.07 | 84 | 3 | — | <10 | 3 | ||
| 18 | 2,2-dimethylprogesteronea | 6.31 ± 0.16 | 99 | 3 | — | <10 | 3 | ||
| B Ring | 19 | 6β-methylprogesteronea | 6.58 ± 0.12 | 90 | 3 | — | <10 | 3 | |
| 20 | 6α-methylprogesteronea | 6.16 ± 0.14 | 96 | 3 | 6.62 ± 0.20 | 18 | 3 | ||
| 21 | 6β-hydroxyprogesterone | 6.91 ± 0.10 | 116 | 3 | 6.72 ± 0.09 | 35 | 3 | ||
| 22 | 5α-hydroxy-6β-methylpregnan-3,20-dionea | 5.30 ± 0.55 | 95 | 3 | — | <10 | 3 | ||
| C Ring | 23 | 11β-hydroxyprogesterone | 7.73 ± 0.13 | 90 | 5 | 7.54 ± 0.55 | 52 | 4 | |
| 24 | 11α-hydroxyprogesterone | 6.90 ± 0.08 | 100 | 3 | 6.93 ± 0.45 | 32 | 4 | ||
| D Ring | 25 | 17α-hydroxyprogesterone | 7.98 ± 0.35 | 115 | 5 | 8.02 ± 0.36 | 67 | 3 | |
| 26 | 3α,5β-THDOC | 5.80 ± 0.26 | 100 | 3 | 5.98 ± 0.39 | 18 | 4 | ||
| 27 | 3α,5α-THDOC | 6.05 ± 0.21 | 96 | 6 | 6.20 ± 0.26 | 37 | 4 | ||
| 28 | 16α-hydroxyprogesterone | 6.77 ± 0.18 | 106 | 3 | 6.71 ± 0.27 | 47 | 3 | ||
| 29 | 17α-acetoxyprogesterone | <5 | 31 | 8 | <5 | 37 | 3 | ||
| 30 | 17α-hydroxy-6α-methylprogesterone | 6.33 ± 0.10 | 96 | 3 | — | <10 | 3 | ||
The potency (EC50 values, mean ±SD) and maximum response (Emax) produced by each compound was determined in the absence and presence of 30 µM mibefradil. Emax is expressed as a percent of the response produced by a saturating concentration of PROG (3 µM). The number of independent experiments indicated by n. Fitted parameters were not calculated for compounds producing Emax < 10%.
↵aSynthesized compound (see Supplemental Schemes 1–3 and Synthetic Procedures for synthesis and characterization).