Structure-activity relationships for unsaturated dialdehydes. 6. The mutagenic activity of 11 compounds in the V79/HGPRT assay.

The mutagenic activity of 11 sesquiterpenoid unsaturated dialdehydes in the V79/HGPRT assay has been determined, and is compared with previously published data on the mutagenicity of the same compounds towards Ames Salmonella strains. One compound, isovelleral, is a potent mutagen in both assays, while six compounds, which are positive in the Ames Salmonella/microsome assay, show no significant activity in this study. One compound, acetylmerulidial, is negative in the Ames Salmonella/microsome assay but significantly although weakly mutagenic in the V79/HGPRT assay. The remaining three compounds are inactive in both assays. The study is part of a general investigation of quantitative structure-activity relationships for unsaturated dialdehydes, a class of natural occurring compounds known for their potent and numerous biological activities.     

Studies on plant growth-regulating substances. XXIX. The plant growth-retarding properties of certain quaternary ammonium halides

The plant growth-retarding activity of a series of N-methyl-N-chloro-alkyl-pyrrolidinium and -piperidinium halides has been measured using wheat and barley seedlings and dwarf bean plants. Some of these compounds possess activity comparable to that of 2-chloroethyl-trimethyl-ammonium chloride (CCC). The activities of twenty-four quaternary halides of pyridine, N-methyl-pyrrolidine and N-methylpiperidine, each possessing a chlorinated benzyl group, have also been determined in the wheat seedling and dwarf bean tests. Many of these compounds were active and activity could be correlated with the substitution pattern in the benzyl group.     

Bioactive sesquiterpenes from Santolina rosmarinifolia subsp. Canescens. A conformational analysis of the germacrane ring.

The hexane extract of aerial parts of Santolina rosmarinifolia subsp. canescens afforded eight new sesquiterpenes in addition to known compounds. Their structures were determined by spectroscopic methods and chemical transformations. The conformational analysis of the germacrane constituents was carried out by spectroscopic methods, including NMR at varying temperature and by molecular mechanics calculations. The antifeedant, antibacterial and antitumoral activity of selected compounds has been tested.     

Antioxidant components of Laetiporus sulphureus (Bull.: Fr.) Murr. fruit bodies

Antioxidant activity of fruit bodies of Laetiporus sulphureus (Bull.: Fr.) Murr. (Polyporales) obtained by the natural plantation growing method in Pribaikal'e (Irkutsk region) has been studied. It was determined that the ethyl acetate fraction of L. sulphureus, which was chromatographically separated into seven compounds identified as quercetin, kaempferol, (+)-catechin, p-coumaric, gallic, caffeic, and chlorogenic acids was characterized with more expressed antioxidant activity. All compounds were extracted from this basidiomycete species for the first time. The quantitative amount of the substances isolated from L. sulphureus was determined by HPLC. It was found that antioxidant activity of preparations obtained from L. sulphureus is conditioned by phenolic compounds.     

Studies on plant growth-regulating substances. XLIX. Phenoxyalkenes

A series of phenoxyalkenes has been examined in a number of tests for plant growth-regulating and selective herbicidal properties. Some of these compounds were found to possess high activity. The results are discussed in terms of chemical structure/biological activity relationships and mode of action.     

Effect of five-membered heterocycles against Leishmania donovani infection.

Impact of change of heteroatom in pentavalent heterocycles, viz., pyrroles, isoxazoles, imidazoles and crotonates on the profile of antileishmanial activity against amastigotes of L. donovani using in vivo test system and macrophage-amastigote culture system has been studied. Sixty-three compounds were tested. Nine imidazoles showed marginal activity in vivo, whereas 3 out of 10 compounds of isoxazolone series and 2 out of 4 substituted aminocrotonates exhibited antileishmanial activity. Of the 30 substituted pyrroles, except 8 all showed antileishmanial activity in vivo on day 7 post treatment.     

The effects of some pharmacologically active amines on the rate of gastric emptying in rats.

The effects of several pharmacologically active amines on gastric emptying rate in male rats has been investigated. Of the compounds tested those with anticholinergic activity; amitriptyline, nortriptyline, imipramine, desmethylimipramine, 3-methylamino-1:1-diphenyl-prop-1-ene and its primary and tertiary amine analogues, dexamphetamine and methylamphetamine, all inhibited gastric emptying of a non-absorbable marker, polyethylene {1,2?¹⁴C} glycol. The compounds with little or no anticholinergic activity did not affect gastric emptying. The activity of the compounds in inhibiting gastric emptying falls in approximately the same order as their anticholinergic activity, lending support to the hypothesis that inhibition of gastric emptying is $\text{via}$ in anti-cholinergic mechanism. The results also indicate that absorption is a prerequisite of activity in inhibiting gastric emptying and suggests that these compounds are not acting $\text{via}$ a local mechanism.     

Anti-tubercular agents. Part IV: Synthesis and antimycobacterial evaluation of nitroheterocyclic-based 1,2,4-benzothiadiazines

In continuation of our earlier work on benzothiadiazines, we have prepared a series of nitrofuran, nitrothiophene and arylfuran coupled benzothiadiazines and evaluated them for antimycobacterial and antibacterial activities. One of the compounds 2f has shown good in vitro antimycobacterial activity. All the synthesized compounds have shown moderate to good antibacterial activity.     

Compounds of Mo, V and W in biochemistry and their biomedical activity.

Molybdenum, vanadium and tungsten compounds are widely applied as analytical reagents for determination of numerous pharmacologically active substances and different biochemical parameters. Recent data from the available literature pointed to a very potent biomedical activity of compounds containing these trace elements. The present paper represents a survey on the structure and chemical properties of these compounds, as well as on their biological activity, mostly based on their interaction with cations of biomolecules, such as phospholipids and proteins. Besides, their potent inhibitory effects on cellular targets, bacterial and viral DNA and RNA polymerases will be discussed, as well. Numerous authors clearly demonstrated the antiviral (especially anti-HIV), anticoagulant and antineoplastic properties of the compounds containing the above trace elements. It has been also shown that these compounds act on some cellular enzymatic systems leading to the normalisation of blood pressure, blood glucose and serum lipid levels. Also, compounds of these trace elements represent potent antiobesity agents and express hepatoprotective and antioxidative stress activity.     

Investigations on fungicides: XV. The fungitoxicity and systemic antifungal activity of N-(2, 2, 2-trichloro-1-methoxyethyl) formamide and related compounds

The direct and systemic antifungal activity of 100 compounds structurally related to iV-(2, 2, 2-trichloro-i-methoxyethyl)formamide has been measured. Some of the compounds showed either protectant or systemic activity against powdery mildew fungi. Compounds not possessing a terminal formamido group showed little anti-mildew activity and for good systemic activity an alkyloxy or alkylamino side-chain in the molecule appeared to be necessary.     

Novel potent inhibitors of A. thaliana cytokinin oxidase/dehydrogenase

The synthesis of a new group of 2-X-6-anilinopurines, including compounds with potential cytokinin-like activities, with various substitutions (X=H, halogen, amino, methylthio or nitro) on the phenyl ring is described. The prepared compounds have been characterized using standard physico-chemical methods, and the influence of individual substituents on biological activity has been compared in three different bioassays, based on the stimulation of tobacco callus growth, retention of chlorophyll in excised wheat leaves and the dark induction of betacyanin synthesis in Amaranthus cotyledons. The biological activity of the prepared compounds was also assessed in receptor assays, in which the ability of the compounds to activate the cytokinin receptors AHK3 and AHK4/CRE1 was studied. Finally, the interactions of the compounds with the Arabidopsis cytokinin oxidase/dehydrogenase AtCKX2 (heterologously expressed) were investigated. Systematic testing led to the identification of two very potent inhibitors of AtCKX2: 2-chloro-6-(3-methoxyphenyl)aminopurine and 2-fluoro-6-(3-methoxyphenyl)aminopurine.     

Synthesis and SAR studies of 1-substituted-n-(4-alkoxycarbonylpiperidin-1-yl)alkanes as potent antiarrhythmic agents.

Synthesis and SAR studies of the title compounds have resulted in the identification of structural and physicochemical parameter (Vw) contributing for antiarrhythmic activity. Among the two most promising compounds 3a & 3b, the 3a has shown antiarrhythmic activity comparable to quinidine.     

Glucosyl Zeatin and Glucosyl Ribosylzeatin from Vinca rosea L. Crown Gall Tumor Tissue

Recently detected but unidentified cytokinin activity in crown gall tumor tissue from Vinca rosea L. grown on media containing sources of reduced nitrogen has now been attributed to two adenine-type cytokinins. These compounds are glucopyranosyl derivatives of zeatin and ribosylzeatin. The substitution in each case is on the isopentenyl chain of the parent compound. Neither of these compounds had activity in the soybean callus bioassay at concentrations lower than 1 nm whereas zeatin had activity at 0.1 nm.     

Synthesis and anticonvulsant activity of 3-aryl-5H-2,3-benzodiazephine AMPA antagonists.

A novel series of 3-aryl-5H-2,3-benzodiazepines with N-3 aromatic substituents has been synthesized. Good in vivo anticonvulsant activity of the new compounds has been demonstrated employing the maximal electroshock seizure test in mice. Evaluation of a subset of the compounds in the cortical wedge assay confirmed the new structures to be AMPA antagonists.     

Pyrazolobenzodiazepines: Part I. Synthesis and SAR of a potent class of kinase inhibitors

A novel series of pyrazolobenzodiazepines 3 has been identified as potent inhibitors of cyclin-dependent kinase 2 (CDK2). Their synthesis and structure–activity relationships (SAR) are described. Representative compounds from this class reversibly inhibit CDK2 activity in vitro, and block cell cycle progression in human tumor cell lines. Further exploration has revealed that this class of compounds inhibits several kinases that play critical roles in cancer cell growth and division as well as tumor angiogenesis. Together, these properties suggest a compelling basis for their use as antitumor agents.     

Modified-peptide inhibitors of amyloid beta-peptide polymerization.

Cellular toxicity resulting from nucleation-dependent polymerization of amyloid beta-peptide (Abeta) is considered to be a major and possibly the primary component of Alzheimer's disease (AD). Inhibition of Abeta polymerization has thus been identified as a target for the development of therapeutic agents for the treatment of AD. The intrinsic affinity of Abeta for itself suggested that Abeta-specific interactions could be adapted to the development of compounds that would bind to Abeta and prevent it from polymerizing. Abeta-derived peptides of fifteen residues were found to be inhibitory of Abeta polymerization. The activity of these peptides was subsequently enhanced through modification of their amino termini with specific organic reagents. Additional series of compounds prepared to probe structural requirements for activity allowed reduction of the size of the inhibitors and optimization of the Abeta-derived peptide portion to afford a lead compound, cholyl-Leu-Val-Phe-Phe-Ala-OH (PPI-368), with potent polymerization inhibitory activity but limited biochemical stability. The corresponding all-D-amino acyl analogue peptide acid (PPI-433) and amide (PPI-457) retained inhibitory activity and were both stable in monkey cerebrospinal fluid for 24 h.     

Antimicrobial activity of the extract and isolated compounds from Baccharis dracunculifolia D. C. (Asteraceae)

Baccharis dracunculifolia D.C. (Asteraceae) is the most important plant source of the Brazilian green propolis. Since propolis is known for its antimicrobial activity, the aim of this work was to evaluate the antimicrobial activities of B. dracunculifolia and some of its isolated compounds. The results showed that the leaves extract of B. dracunculifolia (BdE) presents antifungal and antibacterial activities, especially against Candida krusei and Cryptococcus neoformans, for which the BdE showed IC50 values of 65 microg mL(-1) and 40 microg mL(-1), respectively. In comparison to the BdE, it was observed that the green propolis extract (GPE) showed better antimicrobial activity, displaying an IC50 value of 9 microg mL(-1) against C. krusei. Also, a phytochemical study of the BdE was carried out, affording the isolation of ursolic acid (1), 2a-hydroxy-ursolic acid (2), isosakuranetin (3), aromadendrin-4'-methylether (4), baccharin (5), viscidone (6), hautriwaic acid lactone (7), and the clerodane diterpene 8. This is the first time that the presence of compounds 1, 2, and 8 in B. dracunculifolia has been reported. Among the isolated compounds, 1 and 2 showed antibacterial activity against methicillin-resistant Staphylococcus aureus, displaying IC50 values of 5 microg mL(-1) and 3 microg mL(-1), respectively. 3 was active against C. neoformans, showing an IC50 value of 15 microg mL(-1) and a MIC value of 40 microg mL(-1), while compounds 4-8 were inactive against all tested microorganisms. The results showed that the BdE, similar to the GPE, displays antimicrobial activity, which may be related to the effect of several compounds present in the crude extract.     

Effect of actoprotectors on Ca, Mg-dependent ATPase activity in the sarcoplasmatic reticulum of rabbit muscles

The effect of different chemical compounds on Ca, Mg-dependent ATPase (Ca-ATPase) sarcoplasmic reticulum (SR) hydrolytic activity as well as their actoprotecting (AP) activity, the ability to increase organism's resistance under muscle stress and antihypoxanthic (AH) activity to increase the organism's survival under conditions of low pressure has been studied. The compounds with AP-activity have been shown to be strong inhibitors of Ca-ATPase SR hydrolytic activity. No correlation between AP-activity of the compounds and their effect on Ca-ATPase SR has been found. The membranotropic activity of actoprotectors has been shown by electronic paramagnetic resonance method. A suggestion has been made to use Ca-ATPase SR as a tested object during the forecasting actoprotecting activity of new chemical compounds.