Gyorgy Matolcsy

Effect of support characteristics on the determination of the lipophilicity of some neutral, acidic and alkaline compounds by reversed-phase thin-layer chromatography

The lipophilicity of some neutral, acidic and alkaline compounds was determined by reversed-phase thin-layer chromatography applying silica, aluminium oxide and cellulose in different degrees impregnated with paraffin oil as support. The lipophilicity of all compounds increased on all supports at increasing extent of impregnation; paraffin oil gradually covered the active adsorption sites of supports. The lowest RM values were determined on cellulose support owing to its lower adsorptive capacity. The alkaline compounds showed higher RM values on silica and the acidic compounds on aluminium oxide, proving that also the surface pH value of the support influences the lipophilicity determination.

Anomalies in the reversed-phase thin-layer chromatographic behaviour of some heterocyclic quaternary ammonium salts

Abstract The determination of the lipophilicity of 3,3,5-trimethyl-1-azocycloheptane- and 1,3,3-trimethyl-6-azobicyclo[3.2.1]octane derivatives by reversed-phase thin-layer chromatography shows marked anomalies. In ion-free eluent systems the RM values show an extremely small dependence on the proportio of organic solvent solvent in the mobile phase. A logarithmic relationship was found between the RM value and the pH of the eluent system. The effect of ion concentration can be modelled by a polynomial function. These anomalies can be explained by the change in the ion-pair formation of the very hydrophilic quaternary ammonium group and by the change in the solvate shell around the very lipophilic organic part of the molecule caused by different pH values and by different ion concentrations.

New trifluoropropanone sulfides as highly active and selective inhibitors of insect juvenile hormone esterase

Abstract A series of α,α′-bis(2-oxo-3,3,3-trifluoropropylthio)alkanes was synthesized by the alkylation of the appropriate α,α′-alkanedithiol with 3-bromo-1,1,1-trifluoropropan-2-one. The compounds were tested for in vitro inhibition of insect juvenile hormone esterase (JHE), electric eel acetylcholinesterase (AChE), porcine carboxylesterase, and yeast lipase. Inhibition of hemolymph JHE from fifth instar larvae of the cabbage looper, Trichoplusia ni (Hubner) (Lepidotera: Noctuidae), was in the nanomolar range for many compounds. The inhibition of the other three enzymes was only moderate in comparison to JHE. The inhibition of JHE was compared to carbon chain length, differing heteroatoms, and presence of methyl side-chains. The most effective compound was 1,1,1,16,16,16-hexafluoro-4,13-dithiahexadecane-2,15-dione ( I 50 : 8.2 × 10 −10 M ). The kinetics of inhibition were found to be time-dependent against both JHE and AChE enzymes using representative compounds of both high and low inhibitory potential. Second-order inhibition velocity constants were determined and found to be in agreement with the I 50 values.

Role of β-alanine in pupal cuticle coloration in the tobacco hornworm, Manduca sexta: Effects of β-alanine analogues on melanization and catecholamine levels

Abstract Hydrazino and aminooxy derivatives of β-alanine were found to cause blackening of Manduca sexta pupal cuticle when they were injected into pharate pupae at the onset of pre-ecdysial tanning. One of these compounds, ethyl hydrazinoacetate (EHA), was used for further study. It was effective if injected up to about 4 hr before pupal ecdysis. These melanized cuticles contained excessive amounts of dopamine and decreased amounts of N - β -alanyldopamine (NBAD) and N -acetyldopamine (NADA). Furthermore, EHA induced elevated dopamine and lowered β-alanine levels in the hemolymph. Similar blackening occurred when 20 mg/animal dopamine was injected. Injection of excess β-alanine rescued the normal brown color, irrespective of the concentration of EHA. Also, EHA caused melanization in vitro in the presence of dopamine, whereas the addition of β-alanine and NBAD allowed normal pupal coloration in vitro . These hydrazino and aminooxy compounds likely interfere with β-alanine synthesis or mobilization and thus with N -acylation of the catecholamines to form NBAD and N - β -alanylnorepinephrine.

Projuvenoids: Synthesis and biological evaluation of sulfenylated, sulfinylated, and sulfonylated carbamates

Applying the proinsecticide principle developed earlier for neurotoxic carbamate insecticides, a series of new N-sulfenylated, N-sulfinylated, and N-sulfonylated derivatives of fenoxycarb were synthesized and evaluated for juvenile hormone mimicking activity. Laboratory evaluations of the compounds using Pieris brassicae and Sitophilus oryzae, as well as field experiments using Bemisia tabaci, showed that several symmetrical biscarbamates with either a sulfenyl or sulfinyl bridge possessed higher activity than the parent carbamate. From the unsymmetrical compounds containing biologically inert derivatizing moieties, one of the sulfenylated biscarbamates also showed improved activity against P. brassicae. The changes in the biological activity of the sulfur-containing derivatives compared to that of the parent compound are attributed to the modified physicochemical characteristics, i.e., increased lipophilicity facilitating penetration, transport, as well as protection of the compound from metabolism.

Inhibition of spiracle and crochet formation and juvenile hormone activity of isothiocyanate derivatives in the tobacco hornworm, Manduca sexta

Abstract The structure-activity relationship of various aliphatic, alicyclic, and aromatic mono- and bisisothiocyanates affecting the growth and development of the tobacco hornworm, Manduca sexta, larva was studied. While topical application of short-chain aliphatic monoisothiocyanates to thirdinstar M. sexta larvae did not affect larval development, aromatic mono- and diisothiocyanates were toxic within the dose range tested. Short-chain alkylene and alicyclic 1,3- or 1,4-bisisothiocyanate derivatives, however, prevented the formation of abdominal spiracles and of crochets on the abdominal prolegs at molts following treatment. Their ED50 values for causing spiracular abnormalities ranged from 25 to 208 nmol/larva. Moreover, long-chain mono- or bisisothiocyanates with structural resemblance to known juvenoids had juvenile hormone activity in the black M. sexta assay (their ED50 range from 0.12 to 4.8 nmol/larva) and, in some cases, the formation of supernumerary sixth-instar larvae was observed. Surprisingly, nonjuvenoidlike bisisothiocyanates derived from α-amino acids ornithine and lysine also showed charateristic juvenile hormone effect in this test system (the ED50 values are 0.11 and 0.34 nmol/larva, respectively). The structural requirements for the two different types of activities as well as hypotheses about the possible mode of actions are also discussed.

Inhibitory effect of an in vivo activated soft analogue of A‐phenyl‐B‐triazolium metyrapone during pupariation in Sarcophaga bullata

Experiments with the ovoviviparous fleshfly Sarcophaga bullata (Parker) (Dipt., Sarcophagidae), showed that the compound 4‐(dodecanoyloxymethyl)‐1‐(2‐methyl‐1‐oxo‐1‐phenyl‐2‐propyl)‐(1,2,4‐triazolium) chloride (NKI‐42002) was an in vivo inhibitor of the cytochrome P‐450‐dependent monooxygenase system (MFO) during pupariation. The hard analogue of A‐phenyl‐B‐triazolium metyrapone and the soft analogue of A‐phenyl‐B‐imidazolium metyrapone showed no specific activity. Our results suggest that the soft quaternary group may help the transport of A‐phenyl‐B‐triazolium metyrapone to the MFO system.

Alkylene-bis-isothiocyanates: novel insect growth regulators

In search for selective anti-insect agents some mono- and bis-isothiocyanates were prepared and tested on third instar larvae of Manduca sexta. The alkylene-bis-isothiocyanates 4, 5 and 6 had a novel effect preventing formation of the abdominal spiracles and of the hooks (crochets) at the following molt to the 4th instar. Some of these larvae died in the molt, while spiracles remained absent also in the larvae which were able to molt to the 5th instar. Histological examination indicated a selective destruction of spiracle forming cells. This novel action might serve as starting point of a new approach in selective insect control.

Dithiocarbamate Derivatives as Herbicide Safeners

Abstract The growing environmental and toxicological concern about the dichloroacetamide type herbicide safeners prompted us to search for alternative safener types. Based on analogy considerations, a random screening of structurally unrelated bivalent sulphur compounds was performed, followed by successive structure optimization phases representing both speculative and empirical elements. Dithiocarbamate ester type compounds derived from 1,4-exaza-spiro[4.5]decane revealed highest protecting potency both agains thiolcarbamate and chlor-acetanilide herbicides in corn (Zea mays L.), with the benzylic and allylic esters being the most active.

A rapid method for the evaluation of nerve conduction blocking compounds

A simple and easily accessible cockroach nerve preparation is described. Afferent potentials elicited by electric stimulation of the cercus showed remarkable stability, providing a fairly adequate background for pharmacological experimentation. Type I and type II pyrethroids were tested on the nerve preparation, and the results were compared with toxicity data obtained on the same species. Blockade of nerve conduction showed positive correlation (r = 0.804) with lethal effects. The preparation would be useful for determining neuronal point of attack of test compounds and the study of pyrethroids.