Kazuhiko Oyama

Effect of five-membered cyclic phosphorothionates on larval growth, trehalase, digestive enzymes, acetylcholinesterase, and cyclic adenosine 3′,5′-monophosphate level of Tribolium castaneum and Musca domestica

Abstract The 4-isobutyl (iBMOS) and 5-phenyl (5-PMOS) derivatives of 1,3,2-oxazaphospholidine 2-sulfide suppressed the larval growth, pupation, and emergence of Tribolium castaneum and Musca domestica . Feeding larvae iBMOS or 5-PMOS for 2 days reduced weight gain, suppressed soluble gut trehalase activity, and increased whole body levels of cyclic adenosine 3′,5′-monophosphate (cAMP) relative to control. Invertase was slightly suppressed and neither amylase nor protease was affected in vivo by these phosphorus compounds. At a concentration of 10 −4 M , iBMOS and 5-PMOS had no direct effect on these enzymes in vitro . At a dose needed for 50% mortality (LD 50 ) 20 hr after topical application, 5-PMOS caused a 50% inhibition of M. domestica adult females acetylcholinesterase activity (AChE), 60 min after topical application. T. castaneum larvae fed for 24 hr on a diet containing 80 to 320 ppm iBMOS underwent AChE inhibition of 61 to 86%; cAMP content was increased up to 186% and mortality up to 34%, relative to control. Similar phenomena were observed with 80 to 320 ppm of 5-PMOS. It can be concluded that at sublethal concentrations, these compounds reduced trehalase activity, which is important for energy supply in insects, whereas at lethal concentrations they inhibited AChE activity similar to other acyclic phosphorus compounds.

Effect of salithion enantiomers on the trehalase system and on the digestive protease, amylase, and invertase of Tribolium castaneum

Abstract (R)(+)-Salithion was a more potent inhibitor than (S)(−)-enatiomer on the larval growth, pupation, and emergence of Tribolium castaneum. According to concentration needed for 50% larval weight gain inhibition (IC50), (R)(+)-enantiomer was ∼17-fold more potent than the (S)(−)-enantiomer. Larvae fed for 2 days on dietary concentration of 2 and 4 ppm (R)(+)-salithion resulted in larval weight gain inhibition of ∼10 and ∼55%, correlating well with the inhibition of the activity of the soluble larval gut trehalase. Similar correlation was obtained with 20 and 40 ppm of (S)(−)-salithion. At a concentration of 10−4M, salithion enantiomers had no effect on the trehalase activity in vitro. Hence, the compound affects the biological process, leading to a reduced activity of trehalase in vivo. Both enantiomers had no effect in in vivo assays on the digestive protease and amylase activity. Invertase, which plays a minor role in carbohydrate digestion in Tribolium larvae, as compared to amylase, was inhibited to some extent by salithion enantiomers. Hence, the reduced activity of the trehalase system appears to be an important factor for the growth suppression observed after salithion application.

Effect of insecticidal cyclic phosphorothionates on adenylate cyclase and phosphodiesterase

Abstract Octopamine (0.1 and 1 m M ) stimulated the adenylate cyclase prepared from Periplaneta americana ventral nerve cords (615 and 1112% relative to the control). d -(−)-2-Amino-1-phenylethanol (APE) was more potent than 2-amino-1-(4-fluorophenyl)ethanol (an octopamine agonist) and l -(+)-APE in stimulating the adenylate cyclase. 2-Methoxy-5-phenyl-1,3,2,-oxazaphospholidine 2-sulfide (5-PMOS) derived from dl -(±)-APE did not activate adenylate cyclase at 0.75 and 7.5 m M (91 and 95% relative to the control) but suppressed the octopamine (0.1 m M ) potency to 268% at 1 m M relative to the control. Salithion (2-methoxy-4 H -1,3,2-benzodioxaphosphorin 2-sulfide) at 0.1 m M , fenitrothion (dimethyl 3-methyl-4-nitrophenyl phosphorothionate), 2-amino-1-(2,3-dimethoxy)phenylethanol, 5-PMOS, and other oxazaphospholidines at 1 m M showed similar phenomena. 1-Naphthyl-, 2-naphthyl-, 4-ethylphenyl-, and 4-isopropylphenyloxazaphospholidine derivatives at 0.1 m M reduced the octopamine potency at 0.1 m M more severely than the octopamine-receptor antagonists (chlordimeform and cyproheptadine) at 1 m M . 5-(2,3-Dimethoxyphenyl)-2-methoxy-1,3,2-oxazaphospholidine 2-sulfide ( K i = 107.9 μ M ), fenitrothion ( K i = 37.3 μ M ), and 3-isobutyl-1-methylxanthine ( K i = 1.5 μ M ) reduced the phosphodiesterase activity of beef heart in a competitive manner with respect to cyclic adenosine 3′,5′-monophosphate (cAMP). At 50 μ M , salithion, salioxon (2-methoxy-4 H -1,3,2-benzodioxaphosphorin 2-oxide), and other oxazaphospholidines reduced phosphodiesterase activity. Hence, d -(−)-APE could be an agonist, and 5-PMOS and salithion analogs and fenitrothion could be partial antagonists to the octopamine receptor. The increased level of whole-body cAMP of Musca domestica and Tribolium castaneum larvae treated with these phosphorothionates is due to reduction of phosphodiesterase activity.

Synthesis and insecticidal efficacy of pyripyropene derivatives focusing on the C-1, C-7, and C-11 positions’ substituent groups

The C-1, C-7, and C-11 positions of pyripyropene A were chemically modified to improve the insecticidal activity. Some derivatives showed higher insecticidal activities against aphids than pyripyropene A. In particular, the derivative 5c, which possesses three cyclopropyl carbonyl groups at the C-1, C-7, and C-11 positions, had excellent insecticidal activity levels in field and laboratory trials.