ABSTRACT
The title compound, C(23)H(23)NO(5)·CH(2)Cl(2), was obtained via the alkyl-ation of the 12-hydr-oxy-2,3,8,9-tetra-methoxy-benzo[c]phenanthridine salt. The benzo[c]phenanthridine ring system is essentially planar, with a mean out-of-plane deviation of 0.026â Å. A dicloromethane mol-ecule of solvation is present and located between the sheets of phenanthridine mol-ecules, preventing any significant inter-molecular hydrogen-bonding or π-π inter-actions.
ABSTRACT
Bicyclic analogues of the plant hormone abscisic acid (ABA) were designed to incorporate the structural elements and functional groups of the parent molecule that are required for biological activity. The resulting tetralone analogues were predicted to have enhanced biological activity in plants, in part because oxidized products would not cyclize to forms corresponding to the inactive catabolite phaseic acid. The tetralone analogues were synthesized in seven steps from 1-tetralone and a range of analogues were accessible through a second route starting with 2-methyl-1-naphthol. Tetralone ABA 8 was found to have greater activity than ABA in two bioassays. The absolute configuration of (+)-8 was established by X-ray crystallography of a RAMP hydrazone derivative. The hydroxymethyl compounds 10 and 11, analogues for studying the roles of 8- and 9-hydroxy ABA 3 and 6, were also synthesized and found to be active.
Subject(s)
Abscisic Acid/analogs & derivatives , Abscisic Acid/chemistry , Tetralones/chemistry , Tetralones/chemical synthesis , Abscisic Acid/pharmacology , Arabidopsis/drug effects , Arabidopsis/physiology , Germination/drug effects , Models, Molecular , Molecular Conformation , Plant Growth Regulators/chemistry , Seeds/drug effects , Seeds/physiology , Spectroscopy, Fourier Transform Infrared , Tetralones/pharmacologyABSTRACT
Analogues of the antimalarial alkaloid nitidine have been prepared with high potency against both chloroquine-sensitive and -resistant strains of Plasmodium falciparum in vitro. Simple modifications, using an established synthetic route, resulted in an analogue with IC(50) below 5ng/mL against a chloroquine-sensitive strain of P. falciparum. N-Ethylethoxidine had IC(50) below 30ng/mL against both chloroquine-sensitive and chloroquine-resistant strains of P. falciparum.
Subject(s)
Antimalarials/chemistry , Phenanthridines/chemistry , Plasmodium falciparum/drug effects , Animals , Antimalarials/pharmacology , Humans , Microbial Sensitivity Tests , Netropsin/chemistry , Netropsin/pharmacology , Phenanthridines/pharmacology , Plasmodium falciparum/physiologyABSTRACT
An affinity probe has been developed for isolation of receptor proteins that bind the plant hormone abscisic acid (ABA). The structural features required for biological activity have been preserved, and the probe has been demonstrated to bind to known ABA-binding proteins.
