Anticytokinin activity of substituted pyrrolo[2,3- d ]pyrimidines

Abstract

Ten substituted pyrrolo[2,3-dpyrimidines were tested as cytokinins and anticytokinins in the tobacco bioassay. Eight new anticytokinins were identified and two were found to be highly active. The most potent species were 4-cyclohexylamino-and 4-cyclopentylamino-2-methylthiopyrrolo[2,3-djpyrimidine, of which 0.05 and 0.009 AM concentrations, respectively, were required to produce detectable inhibition of the growth of tobacco callus cultured on a medium containing 0.003 uM 6(3-methyl-2-butenylamino)purine. The inhibition of growth by moderate (<6.6 uM) concentrations of these compounds was reversible by equal or higher concentrations of 6-(3-methyl-2-butenylamino)purine, but not by indole-3-acetic acid or gibberellic acid. These substituted pyrrolo[2,3-djpyrimidines were also found to enhance bud formation at high cytokinin concentrations, suggesting that a cytokinin may act at more than one cellular site in exerting its growth-promoting and morphogenetic effects.Cytokinins are a class of hormones which promote cell division and participate in the regulation of growth and morphogenesis in plants (1). Although all plants are thought to require cytokinins for growth, intact plants generally grow without exogenous cytokinins, presumably because they make their own. In fact, several highly active cytokinins have been found to occur naturally as N6-substituted adenine derivatives at the purine, ribonucleoside, and ribonucleotide levels (1). Cytokinins are also present in the transfer RNA's of most forms of life, although their presence in tRNA has not been shown to be related to their regulation of growth (1, 2).Cytokinins have been found to influence the behavior of mammalian cells. They have been reported, for example, to inhibit platelet aggregation (3) and the growth of several mammalian cell lines, including cancerous lines (4-6 and references in 5). N6-(3-Methyl-2-butenyl)adenosine (i6Ado) has been reported to be an immunosuppressive agent (7) and to induce hematological remissions in leukemia patients (8,9). Several cytokinins, including i6Ado, have also been shown to be capable of regulating the growth of phytohemagglutinin-transformed human lymphocytes (10 and references therein), presumably by involvement in cyclic AMP metabolism, and i6Ado was shown to act as a competitive inhibitor of beef heart cyclic AMP phosphodiesterase (11).To facilitate the study of the mechanism of cytokinin action and provide potential chemotherapeutic agents, we designed and synthesized a class of structural analogs of cytokinins which behave as anticytokinins in plant bioassays (12,13). Proof that these "anticytokinins" act at the same cellular sites as the cytokinins is not presently accessible, since cytokinin-anticytokinin interaction is not monitored at the molecular level, but this interpretation has been proposed on the basis of the observed biological activities of the analogs in several assays and on the close structural relationship between cytokinins and anticytokinins (14). The successful preparation of a class...

Two Effects of Cytokinin on the Auxin Requirement of Tobacco Callus Cultures

“…Two strains of tissue that arose in this manner (designated I and II in Table I) were subcultured for 15 bimonthly passages on medium without IAA but containing 5 AM i6Ade. (12).…”

Unraveling plant hormone signaling through the use of small molecules

“…In the seventies, several synthetic CK derivatives, such as pyrazolo[4,3-d]pyrimidines (Hecht et al, 1971; Skoog et al, 1973), pyrrolo[2,3-d]pyrimidines (Iwamura et al, 1974, 1975) and 7-deaza analogs of 2-methylthioadenine CK (Skoog et al, 1975) were classified as anti-CKs. It was later shown that these compounds do not act as CK antagonists on CK receptors, as was initially suspected, but that at least some of them act as cyclin-dependent kinase inhibitors (Sṕichal et al, 2007; Arata et al, 2010).…”

Quantitative Structure-Activity Relationships of Insecticides and Plant Growth Regulators: Comparative Studies toward Understanding the Molecular Mechanism of Action

“…In this respect, quite a few structural classes of cytokinin antagonists, anticytokinins, have been developed recently (44)(45)(46)(47)(48) adenylate cytokinins in the preceding section, providing us with an insight into the bulkiness of the receptor cavity into which the alkyl substituents must fit. In this respect, quite a few structural classes of cytokinin antagonists, anticytokinins, have been developed recently (44)(45)(46)(47)(48) adenylate cytokinins in the preceding section, providing us with an insight into the bulkiness of the receptor cavity into which the alkyl substituents must fit.…”