Synthesis and structure-activity relationships of new pyrazole derivatives that induce triple response in <i>Arabidopsis</i> seedlings

Abstract

Twenty-seven analogues of pyrazole derivatives were synthesized and subjected to structure-activity relationship studies on inducing the triple response in Arabidopsis seedlings. We found that 3,4-Dichloro-N-methyl-N-[(1-allyl-3,5-dimethyl-1H-pyrazol-4-yl)methyl]benzenesulfonamide (C26) exhibits potent activity on inducing the triple response in Arabidopsis seedlings. C26 (10 µM) induced an exaggerated apical hook in Arabidopsis seedlings. The curvature of the hook of the Arabidopsis seedlings was found to be 300±23 degrees, while ethephon (10 µM), a prodrug of ethylene, and a non-chemically treated control were found to be 128±19 and 58±16 degrees, respectively. C26 also exhibited potent activity on reducing stem elongation. The hypocotyl length of Arabidopsis seedlings treated with C26 (10 µM) was found to be 0.25±0.02 cm, while those of ethephon-treated (10 µM) and treated controls were found to be 0.69±0.06 and 1.15±0.01 cm, respectively. C26 displayed potency inhibiting the root growth of Arabidopsis seedlings similar to that of ethephon.

Synthesis of fluorescently labeled pyrazole derivative induceing a triple response in <i>Arabidopsis</i> seedlings

“…We have previously shown that the modifications of the sulfonamide moiety did not significantly influence the biological activity of EH-1 . 14 ) Thus, introducing a dansyl moiety to EH-1 represents a straightforward approach to developing fluorescence-labeled EH-1 . Dansyl chloride (5-(dimethylamino)naphthalene-1-sulfonyl chloride) is a reagent that reacts with amines to produce stable blue or blue-green fluorescent sulfonamide adducts that display sufficient fluorescence properties.…”

“…The general procedure for preparing N -methyl- N -[(1,3,5-trimethyl-1 H -pyrazol-4-yl)methyl]-5-dimethylamino-1-naphthalenesulfonamide ( EH-DF ) was carried out by reacting N -methyl-1-(1,3,5-trimethyl-1 H -pyrazol-4-yl)methanamine with dansyl chloride in a condition as we described previously. 14 ) (yield: 33%), oil, 1 H NMR (400 MHz, CDCl 3 ); δ: 2.01 (s, 3H), 2.07 (s, 3H), 2.63 (s, 3H), 2.89 (s, 6H), 3.67 (s, 3Hs), 4.08 (s, 2H), 7.19 (d, J =7.3 Hz, 1H), 7.52–7.57 (m, 2H), 8.21 (d.d, J1=1.2, J2=7.3 Hz, 1H), 8.45 (d, J =8.6 Hz, 1H), 8.57 (d, J =8.6 Hz, 1H); 13 C NMR (100 MHz, CD 3 OD): δ 152.9, 148.2, 140.5, 135.1, 134.2 (x2), 131.4, 131.1, 130.8, 128.9, 124.2, 120.7, 116.7, 116.3, 111.5, 51.8, 45.6, 43.8, and 33.5. The HRMS-ESI calculated for C 20 H 26 N 4 O 2 S [M+H]+ was 386.1776, and we found 386.1759.…”

“…The general procedure for preparing N-methyl-N-[ (1,3,5-trimethyl-1H-pyrazol-4-yl) methyl]-5-dimethylamino-1-naphthalenesulfonamide (EH-DF) was carried out by reacting N-methyl-1-(1,3,5-trimethyl-1H-pyrazol-4-yl) methanamine with dansyl chloride in a condition as we described previously. 14) (yield: 33%), oil, 1…”

“…The synthesis of EH-DF was carried out by reacting dansyl chloride with commercially available N-methyl-1-(1,3,5-trimethyl-1H-pyrazol-4-yl) methanamine (Sigma-Aldrich) in a condition we described previously (Scheme 1). 14) Scheme 1. General synthetic route for preparing EH-DF.…”

“…In a previous work, we carried out a structure-activity relationship study of EH-1, and we found that the pyrazole moiety of EH-1 displayed an important effect on promoting the biological activity. 14) Based on this observation, the sulfonamide moiety of EH-1 is a good candidate for introducing a fluorophore to EH-1, thereby developing fluorescence-labeled chemicals with ethylenelike biological activity. In the present work, we report the synthesis of N-methyl-N-[(1,3,5-trimethyl-1H-pyrazol-4-yl) methyl]-5-dimethylamino-1-naphthalenesulfonamide (EH-DF); we also determined the biological activity of EH-DF and discussed the application of EH-DF.…”