Synthesis and radioprotective study of new siladithioacetals and germadithioacetals

A series of organosilicon and organogermanium compounds derived from cysteamine, methylcysteamine and 2‐[1‐(1‐naphthyl)ethyl]‐2‐imidazoline have been prepared and their radiopharmacological properties (radioprotective activity and toxicity) have been determined in mice. A number of these new organometallic derivatives have been found to possess radioprotective activity. We have also noted a notable decrease of the toxicity and a fairly large increase in the radioprotective activity in comparison with the unsubstituted organic molecules. Copyright © 2003 John Wiley & Sons, Ltd.     

Synthesis and radiopharmacological study of new metallated thiazolidines and dithioacetals of N-allyl-substituted cysteamine and methylcysteamine

New germa- and silathiazolidines or germa- and siladithioacetals with N-allyl-substituted cysteamine and methylcysteamine ligands have been synthesized and their pharmacological properties (toxicity, radioprotective activity) have been studied. A notable decrease in the toxicity and a rather large increase in the radioprotective activity of these new organometallic derivatives compared to N-allyl-substituted cysteamine and methylcysteamine were observed.     

Radioprotective activity of metalladithioacetals derived from N‐substituted naphthylethylimidazoline

A number of organosilicon and organogermanium derivatives of N‐substituted 2‐[1‐(1‐naphthyl)ethyl]‐2‐imidazoline have been reported and the toxicity of these compounds has been determined in mice. In this paper we report the evaluation of the radioprotective activity of new sila‐ and germa‐dithioacetals derived from N‐substituted 2‐[1‐(1‐naphthyl)ethyl]‐2‐imidazoline. Copyright © 2003 John Wiley & Sons, Ltd.     

New Germaheterocycles,Germadithioacetals and a Germylated Oxide and Sulfide Derived from Cysteamine,Methylcysteamine and N-Substituted Cysteamine: Synthesis and Radioprotective Activity

Further to our work concerning organometallic compounds active in chemical radioprotection, we report the synthesis and pharmacological study (radioprotective activity, toxicity) of new germathiazolidines and germadithioacetals derived from cysteamine, methylcysteamine and N -substituted cysteamine. A germylated oxide and sulfide with methylcysteamine hydrochloride as ligand were also investigated. A notable decrease in the toxicity and a fairly large increase in the radioprotective activity of these new organogermylated compounds were observed compared with cysteamine, methylcysteamine and N -substituted cysteamine.     

Structure-function analysis of the radioprotective and antioxidant activity of flavonoids

The recombination kinetics of a series of flavonoids with stable DPPH radicals are studied. Flavonols are the most reactive. Polarization of the carbonyl in flavones reduces the reactivity. Substitution on C-7 and the B ring has practically no effect on the reactivity. Glycosylation of C-3 reduces the reactivity if the sugar can form two intramolecular H-bonds. The reactivity of the flavonoid phenol hydroxyls, with the exception of the hydroxyl on C-5, is proportional to their number. The most promising antioxidants are lespedin, kaempferitrin, kaempferol, kaempferol-7-rhamnoside, kaempferol-3-robinobioside, and robinin.I. G. Kutateladze Institute of Pharmacochemistry, Georgian Academy of Sciences, Tbilisi, fax (99532)-25-00-26. Translated from Khimiya Prirodnykh Soedinenii, No. 1, pp. 42–46, January–February, 2000.     

Synthesis and application of new organometallic compounds of silicon and germanium in chemical radioprotection

Several organosilicon and organogermanium compounds possessing radioprotective activity have been synthesized. In this paper, we describe the preparation and study of the pharmacological properties of new organometallic compounds such as metallathiazolidines and metalladithioacetals derived from 1‐[N‐(2‐mercaptoethyl)‐­2‐aminoethyl] ‐ 2 ‐ (1‐naphthylmethyl) ‐2‐ imidazoline and 1‐[N‐(2‐mercaptopropyl)‐2‐aminoethyl]‐2‐(1‐naphthylmethyl)‐2‐imidazoline. We have noted a decrease in the toxicity and a rather important increase in the radioprotective activity of these new organometallic derivatives in comparison with the starting organic compounds. Copyright © 1999 John Wiley & Sons, Ltd.     

茶多酚锗的合成及测试

茶多酚锗的合成及测试卢玉振＊张长庚（贵州大学化学系贵阳５５００２５）关键词茶多酚，茶多酚锗，合成，ＬＤ５０１９９６－０３－２６收稿，１９９６－０７－０２修回自从发现一些滋补性药用植物如人参、枸杞子等都含有微量锗以来，有机锗化合物的生化效应研究促进了有...     

The acute toxicity of tri-n-butyltin taurocholate

The acute toxicity for tri-n-butyltin taurocholate (TBT-TA), a newly synthesized organotin steroid, was determined using Long Evans rats. The organotin compound was suspended in corn oil and administered by gavage using standard techniques. The TBT-TA exhibited a taurocholic acid toxicity at 24 h and a tributyltin toxicity at three days. The LD₅₀ values were 611 and 384 mg kg^?1 respectively. The dead rats exhibited distended stomachs, enlarged cecums, and lesions in the gastrointestinal tract. The toxicity is similar to that observed with other trialkyltin compounds.     

The acute toxicity of tri-n-butyltin glycocholate

The oral acute toxicity for tri-n-butyltin glycocholate (TBT-GA), a newly synthesized organotin steroid, was determined using Long Evans rats. The compound was suspended in corn oil and adminstered by gavage using standard techniques. Unlike tri-n-butyltin taurocholate, which exhibited two different toxicities, one for the tri-n-butyltin moiety and one for the taurocholic acid moiety, the TBT-GA exhibited a single toxicity, that of the whole molecule. The LD₅₀ value was 213 mg kg^?1 (0.274 mmol kg), which on a millimolar basis is similar to that observed for other tri-n-butyltin compounds. The dead rats exhibited distended stomachs, enlarged ceca, and lesions in the intestinal tract. The actual cause of death could not be positively identified. Animals that survived more than three days also exhibited time- and dose-related atrophy of the thymus gland. With 36% more male than female rats succumbing to TBT-GA, the chemical appears to be more toxic towards male than female rats.     

氟化钠对小鼠的急性毒性实验研究

为探讨氟化钠对小鼠的急性毒性及反应,采取灌胃法给小鼠一次性给药,观察了7 d内35.00、55.56、88.18、139.97、222.18、352.67、559.79 mg/kg等7个剂量组小鼠的毒性反应和死亡情况,计算了氟化钠经口半数致死量(LD50)及95%可信限.结果表明,各剂量组中毒小鼠均出现不同程度的抽搐、...     

去氢木香内酯衍生物的合成及其抗炎活性研究

去氢木香内酯是一种含有多种生物活性的倍半萜化合物,广泛存在于药材云木香中。去氢木香内酯与伯胺化合物经Michael加成反应,合成得到5个新的去氢木香内酯衍生物(1～5),其结构均经¹H NMR、¹³C NMR和LC-MS确证。采用小鼠巨噬细胞Raw264.7模型初步测试了衍生物的抗炎活性和毒性,结果表明,化合物1对NO的生成抑制率为88±1.02%,表现出较好的抗炎活性,且在MTT实验中其对巨噬细胞的抑制率仅为3.75%,几乎无细胞毒性,可作进一步研究。     

A comparative study on acute toxicity of methylarsonic acid,dimethylarsinic acid and trimethylarsine oxide in mice

The acute toxicity of methylarsonic acid, CH₃AsO(OH)₂ (MAA), dimethylarsininc acid, (CH₃)₂AsO(OH) (DMAA), and trimethylarsine oxide, (CH₃)₃AsO (TMAO), were examined in mice with oral administration. The LD₅₀ values of MAA, DMAA and TMAO were 1.8, 1.2 and 10.6 g kg^?1 respectively. The toxicity of MAA and DMAA was very much lower than that for inorganic arsenic compounds. It was shown that TMAO has a similar acute toxicity to arsenobetaine. On the other hand, when the mice were administered 14.4 g kg^?1 of TMAO once only orally, a garlic-like odor (trimethylarsine, (CH₃)₃As) was definitely detectable in the exhalation of the animals by the human olfactory sense within about a few minutes.     

Synthesis and neurotropic activity of silyl-substituted fufural thiosemicarbazones

5-Silyl-substituted-2-furaldehyde thiosemicarbazones were prepared by the condensation of the corresponding furfurals or furfural diethylace-tals with thiosemicarbazide. The neurotropic activity of the synthesized thiosemicarbazones has been studied. The majority of the compounds examined possess high or medium neurotropic activity of the depressant type. They also show antihypoxic activity and decrease the duration of phenamine stereotype behaviour. Structure-activity correlation has been found.     

Synthesis of new quinoxalinophenazinediones and tetrahydrobenzodipyrrolotetrones of biological interest

The reaction of two equivalents of sodium azide with diarylaminodibromo-p-benzoquinone (I) in DMF for 15–24 h produced quinoxalinophenazinediones together with a byproduct identified as diarylaminodiaminobenzoquinone. On the other hand, the reaction of bromanil with active methylenes, such as diethyl malonate and ethyl acetoacetate, resulted in disubstitution products which, on treatment with primary amines, cyclized into benzodipyrroletetrones. Comparative antifungal and antibacterial studies were made.     

Synthesis and psychotropic properties of 1-triorganylsiloxy- and 1-triorganylgermoxy-germatranes

Triorganylsiloxy- and triorganylgermoxy-germatranes have been prepared by the interaction of the easily available 1-hydroxygermatrane with various hetaryl-silanes and -germanes. The compounds were of the general structure:

• M = Si; X = S, CH = CH (viz. phenyl); n = 0,1,2
• M = Ge; X = CH = CH (viz. phenyl); n = 0

All siloxy- and germoxy-germatranes obtained were subjected to psychotropic assays. Some of phenylsiloxygermatranes are effective for memory enhancement (inhibition of retrogradal amnesia by triphenylsiloxygermatrane was 80%).     

Synthesis and psychotropic properties of furyl- and thienyl-germatranes

Trihalogermyl-furans and -thiophenes were prepared by inserting germanium dibromide (GeBr₂) generated from the dibromogermane(II) dioxanate complex into the carbon-halogen bond of halo-furans and -thiophenes. Their ethanolysis and transesterification by triethanolamine yielded the germatranes which were subjected to psychotropic activity assays. The psychotropic properties of germatranes were found to depend on the type of the heterocycle and on the position of the germatrane moiety.     

The chemical form and acute toxicity of arsenic compounds in marine organisms

A method for the separation and identification of inorganic and methylated arsenic compounds in marine organisms was constructed by using a hydride generation/cold trap/gas chromatography mass spectrometry (HG/CT/GC MS) measurement system. The chemical form of arsenic compounds in marine organisms was examined by the HG/CT/GC MS system after alkaline digestion. It was observed that trimethylarsenic compounds were distributed mainly in the water-soluble fraction of muscle of carnivorous gastropods, crustaceans and fish. Also, dimethylated arsenic compounds were distributed in the water-soluble fraction of Phaeophyceae. It is thought that most of the trimethylated arsenic is likely to be arsenobetaine since this compound released trimethylarsine by alkaline digestion and subsequent reduction with sodium borohydride. The major arsenic compound isolated from the water-soluble fraction in the muscle and liver of sharks was identified as arsenobetaine from IR, FAB Ms data, NMR spectra and TLC behaviour. The acute toxicity of arsenobetaine was studied in male mice. The LD₅₀ value was higher than 10 g kg⁻¹. This compound was found in urine in the non-metabolized form. No particular toxic symptoms were observed following administration. These results suggest that arsenobetaine has low toxicity and is not metabolized in mice. The LD₅₀ values of other minor arsenicals in marine organisms, trimethylarsine oxide, arsenocholine and tetramethylarsonium salt, were also examined in mice.     

Free radical scavenging and radioprotective effects of carnosine and anserine

Two histidine-containing natural dipeptides, carnosine and anserine (β-alanyl-1-methyl-l-histidine), have been examined for their antioxidant and radioprotective abilities. Pulse radiolysis studies indicated the antioxidative properties of carnosine and anserine aqueous solutions at different pH. The rate constants for the reaction OH radical with carnosine at neutral pH were determined to be 5.3×10⁹ M⁻¹ s⁻¹ at 300 nm, and 4.1×10⁹ M⁻¹ s⁻¹ at 400 nm, respectively. Carnosine and anserine also protected plasmid pUC18 DNA from X-ray radiation-induced strand breaks as evidenced from the studies by agarose gel electrophoresis. Carnosine showed higher protective efficiency under the experimental conditions. Our data demonstrated that carnosine and anserine may play an important role in the maintenance of the antioxidant system.     

Synthesis and Insecticidal Activity of Fire Ant Venom Alkaloid-Based 2-Methyl-6-alkyl-Δ1,6-piperideines

2,6-dialkylpiperideines found in the venom of Solenopsis (Hymenoptera, Formicidae) fire ants are a range of compounds possessing various biological activities. A series of racemic 2-methyl-6-alkyl-Δ^1,6-piperideines were synthesized for chemical confirmation of the natural products found in fire ant venom, and the evaluation of their biological activity. Synthetic Δ^1,6-piperideines and the natural compounds in the cis-alkaloid fraction of Solenopsis invicta had identical mass spectra and retention times. Their insecticidal activities against the third-instar larvae of cotton bollworm (Helicoverpa armigera) were evaluated by using injection and topical application methods. All three compounds exhibited no lethal effect at concentrations of 0.05–0.4 mol/L by topical treatment, but moderate lethal effect at 0.4 mol/L through injection treatment. Compound 6a showed significantly higher activity than the natural insecticide nicotine. The differences in activity among compounds 6b, 6c and nicotine were not significant. The elongation of the carbon chain at the 6-position of the piperideine ring appears to decrease insecticidal activity.     

Acute toxicity and metabolism of arsenocholine in mice

The acute toxicity of arsenocholine was examined in mice by oral administration and intravenous injection. The LD₅₀ values of arsenocholine were 6.5 g kg^?1 for oral administration and 187 mg kg^?1 for oral administration and 187 mg kg^?1 for intravenous injection. Decreases of respiration and spontaneous motility were observed in the mice dosed orally at 12 g kg^?1. The animals exhibited ataxia and finally showed paralysis of the hind legs within 20 min of administration. When arsenocholine was administered orally to mice at 5 or 50 mg As kg^?1, the greater part of the arsenic administered was recovered in urine within 96 h. The metabolite of arsenocholine in urine was identified as arsenobetaine by high-performance liquid chromatography-inductively coupled plasma emission spectrometry (HPLC ICP) and fast atom bombardment mass spectrometry (FAB MS). These results suggested that the major part of orally administered arsenocholine was absorbed from the gastrointestinal tract in mice and then rapidly excreted in urine with biotransformation.