title: Rubrolides as model for the development of new lactones and their aza analogs as potential photosynthesis inhibitors.
abstract: Natural phytotoxins and their synthetic analogs are a potential source of new bioactive compounds for agriculture. Analogs of rubrolides, a class of γ-alkylidene-γ-lactones isolated from different ascidians, have been shown to interfere with the photosynthetic electron-transport chain, yet their activity needs to be improved. With this aim, ten 5-aryl-6-benzyl-4-bromopyridazin-3(2H)-ones were prepared in yields ranging from 44 to 88% by reaction of their correspondent γ-alkylidene-γ-lactones with NH2 NH2 . The structures of these rubrolide analogs were determined by (1) H- and (13) C-NMR, 2D-NMR (COSY and HETCOR), NOE difference, and MS techniques. These compounds were evaluated for their abilities of interfering with the light-driven reduction of ferricyanide by isolated spinach chloroplasts. Lactones with electron-withdrawing substituents in the para-position of the benzylidene ring were the most effective inhibitors. Characterization of the activity of 11b/11b' suggested a mechanism based on the interaction with the plastoquinone binding site of photosystem II. Addition of several compounds to the culture medium of a cyanobacterial model strain was found to inhibit algal growth. However, the relative effectiveness was not consistent with their activity in vitro, suggesting the occurrence of multiple targets and/or detoxyfication mechanisms. Indeed, the compounds showed differential effects on the heterotrophic growth of some crop species, Cucumis sativus and Sorghum bicolor. Pyridazin-3(2H)-ones 12e, 12i, and 12j, which have been found poorly active against the photosynthetic electron transport, were the most effective in inhibiting the growth of some weeds, Ipomoea grandifolia and Brachiaria decumbens, under greenhouse conditions.
authors.affiliation: Department of Chemistry, Federal University of Viçosa, Av. PH Rolfs, Viçosa, MG 36570-000, Brazil.
authors.forename: Ulisses A
authors.initials: UA
authors.lastname: Pereira
authors.affiliation: Department of Chemistry, Federal University of Viçosa, Av. PH Rolfs, Viçosa, MG 36570-000, Brazil. lcab@ufmg.br.|Department of Chemistry, Universidade Federal de Minas Gerais, Av. Pres. Antônio Carlos, 6627, Campus Pampulha, CEP 31270 - 901, Belo Horizonte, MG, Brazil, (phone: +55-31-38993068; fax: +55-31-38993065). lcab@ufmg.br.
authors.forename: Luiz C A
authors.initials: LC
authors.lastname: Barbosa
authors.affiliation: Department of Chemistry, Federal University of Viçosa, Av. PH Rolfs, Viçosa, MG 36570-000, Brazil.
authors.forename: Antônio J
authors.initials: AJ
authors.lastname: Demuner
authors.affiliation: Department of Plant Science, Federal University of Viçosa, Av. PH Rolfs, Viçosa, MG 36570 - 000, Brazil.
authors.forename: Antônio A
authors.initials: AA
authors.lastname: Silva
authors.affiliation: Department of Life Science and Biotechnology, University of Ferrara, via L. Borsari 46, IT-44121 Ferrara (phone: +39-0532-455311).
authors.forename: Michele
authors.initials: M
authors.lastname: Bertazzini
authors.affiliation: Department of Life Science and Biotechnology, University of Ferrara, via L. Borsari 46, IT-44121 Ferrara (phone: +39-0532-455311). flg@unife.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Forlani
mesh_terms: D001372:Aza Compounds / Q000737:chemistry / Q000494:pharmacology*; D035201:Brachiaria / Q000187:drug effects / Q000254:growth & development; D018553:Cucumis sativus / Q000187:drug effects / Q000254:growth & development; D004305:Dose-Response Relationship, Drug; D027741:Ipomoea / Q000187:drug effects / Q000254:growth & development; D007783:Lactones / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D010788:Photosynthesis / Q000187:drug effects*; D045868:Sorghum / Q000187:drug effects / Q000254:growth & development
chemical_list: D001372:Aza Compounds; D007783:Lactones
keywords: Photosynthetic inhibitors; Plant growth regulators; Pyridazin-3(2H)-ones; Rubrolides; γ-Lactones, γ-alkylidene