Biological properties

Biological Properties.—2-(Halogenoacetylamino)-5-methyl-l,3,4-thiadiaz-oles possess antitumour activity against Walker tumours, but are ineffective against Crooker sarcoma.  

2-/ -Methoxybenzenesulphonamido-5-isobutyl-l, 3,4-thiadiazole (179) has hypoglycaemic properties, but produces neoplasms of the urinary bladder in rats, though not in dogs. This difference may possibly be due to the nature of the metabolites produced in the two species. These were isolated from urines by preparative t.l.c. and identified by their mass and n.m.r. spectra. Three metabolites are common to both dog and rat, viz. 2-p-hydroxy-benzenesulphonamido-5-isobutyl-l,3,4-thiadiazole, (180), and (182), derived 

Information is available concerning the cytostatic properties of 2-amino-1,3,4-thiadiazole and its acyl derivatives, and its 5-isopropyl and 5-butyl homologues.  

Certain 1,3,4-thiadiazoles, particularly 2-ureido-derivatives, possess herbicidal activity. - l-Methyl-3-(5-t-butyl-l,3,4-thiadiazol-2-yl)urea controls a broad range of weeds when sprayed on the foliage of the seedlings or the surface of the soil at a dosage of 1—2 kg/hm . The 1,3,4-thiadiazole nucleus appears to play an essential part in the activity, since analogous thiazoles are ineffective. The urea derivatives (184) and (185) (previous 

5-(2-Nitrofuryl-l-furylvinyl)-2-amino-l,3,4-thiadiazoIes and related compounds (59) and (60) exhibit significant activity against staphylococcus. The rate of release of sulphaethylthiadiazole from tablet preparations in acid pepsin and alkaline pancreatin media has been measured.  

For full accounts of biological responses the reader is referred to reviews by Brauer (1965), Helgeland (1982) and Smith (1982b). 

ASM Metals Handbook, Vol. 3 Properties and Selection Stainless Steels, Tool Materials and Special-Purpose Metals. 

Heimann, W. Oppenheim, R. and Weizling, W. (1985) Nichtrostende Stable, in Werkstoffkunde Stahl, Bd. 2 Anwendungen, Springer-Verlag. 

Harris, T. and Priebe E. Forging of Stainless Steels, in ASM Metals Handbook, Vol. 14 Forming and Forging. 

Silicone rubber has been widely used in biomedical applications due to its biocompatibility, nontoxicity and biodurability. Therefore, attempts have been made to further improve the properties of SR by reinforcing it with various inorganic nanofillers [46,189-193]. Zhang eta/. [189] introduced gold nanoparticles in PDMS microfluidic chips and studied its applications in enzyme reactors, immunoassays and biochemical analysis. Recent studies have shown that PDMS-Ag composite exhibits good antibacterial properties 

Carson (109) showed that each of the lysine radicals possessed its -NH2 free and that its a-NH2 was linked in the peptide bond by treating subtilin with nitrous acid or with 2,4-dimtrofluorobenzene. The other free —NH2 groups of subtilin are those of the two sulfur-containing dicarboxylic amino acids. However, for each of these latter residues, only one of their —NH2 groups is free, not both. 

The minimum molecular weight, deduced from the best analyses of certain of the amino acids, is 3420. In fact, diffusion and sedimentation determinations indicate that the real molecular weight, at pH 3.0 at least, is probably twice as much. The significance of these results, considering problems due to molecular association or due to the possibility that the preparation is a mixture of closely related species, is as yet undetermined. 

However this is not a general trend. In particular, the 3-halogen derivatives 62 display strong vasorelaxing activities that are not always correlated with their spontaneous NO-release rates [60]. The effect of thiols on NO-release of these products, discussed above, undoubtedly plays a role in this behavior. 

If maize is for instance infested by caterpillars of the butterfly Spodoptera exigua, then the volicitin (JV-(17-hydroxylinolenyl)-(L)-glutamine) from its 

23 Thus, in respect of signal transduction, jasmonates fulfil a function in plants similar to that of the structurally related prostaglandins in mammals. Furthermore, jasmonates are also involved In the aging process of plants. For example, they inhibit growth, promote the curling of tendrils of climbing plants, and induce tuber formation in potatoes. 

The damage to leaf surfaces in tomato plants leads to the biosynthesis of protease inhibitors, which interfere with the digestive system of the infesting insects and restrict the availability of essential amino acids, eventually retarding growth and development of the pests. 

Most of the experiments were carried out with racemic methyl jasmonate, so that for a long time it was not clear which enantiomer has the higher biological activity. In addition, hydrolysis and epimerisation could not be excluded. [79] 

Dosage/response experiments then showed that the biological activity resides mainly with the primary product, namely the (3H,7S)-jasmonic acid to a lesser extent with its methyl ester. Jasmonic acid does not bind as the free acid, but as a conjugate with isoleucine to the same receptor as coronatine, a phytotoxin produced by Pseudomonas syringae. In this conjugate, epimerisation at C-7, which is associated with a dramatic loss in activity, is used by the plants to regulate hormone activity. [82] 

In some regions where com is essential for human nutrition, the occurrence of esophageal carcinoma has been reported, and this has been associated with fumonisin contamination (211). Concerning the AAL-toxins (see previous section), these were found to be associated with human esophageal cancer, equine leukoencephalomalacia, and liver diseases in humans (272). In the laboratory, these compounds have been shown to inhibit sphingolipid synthesis (213) and to cause apoptosis in tomato cells and green monkey kidney cells (214, 215). 

Bisphenol-A-based polycarbonate is available in different blends which maybe adapted to specific requirements by use of additives. Different Makrolon grades from Bayer AG are designated by a four-digit code, of which the first two digits denote the molecular mass of the polymer (in 1000 g/mol) and accordingly provide information on its chain length. Thus, it may also be a rough classification of the fluidity of the material [5]. 

The oral LD50 for rats is 481 mg/kg ° while the subcutaneous LD50 is 610 mg/kg. ° By ingestion, therefore, maleic anhydride in single doses is considered slightly toxic. No reports of cumulative toxic effects in man have been made. Recently, the Chemical Industry Institute of Toxicology has sponsored a toxicological study of orally administered MA. Hazard in industrial use is essentially that of primary irritation of exposed sur- 

MA is an intense local irritant to body tissue. The irritant effect is exhibited on moist tissues sooner due to MA hydrolysis.The dust and vapor are irritating to skin, eyes, nose, throat, and upper respiratory tract. It has a faint acrid odor noticeable at 0.49 ppm.Although MA is a solid at ambient temperatures, it does have significant vapor pressure. It is also regarded as a sensitizer of the skin and respiratory tract. Its threshold value is recommended at 0.25 ppm (Img/m ) in the workplace.When left in contact with the skin it can cause severe painful irritation. 

Manufacturing Chemists Association data sheet SD-88 gives in detail the fire, explosion, and health hazards. It discusses necessary information for 

From the foregoing, it is apparent that MA is a chemical of considerable commercial importance and potential. It has been and can be handled safely as shown by the experience of the chemical industry over the last 50 years. MA, like all chemicals, should be handled and manipulated with due respect and one using it should be aware of all the potential safety considerations. Information on this is available, as indicated earlier. 

The variety of uses that MA has demonstrated is due to its versatile chemistry. As a result of its unique functionality, it enters into a variety of reactions in addition to the usual functional group reactions. These aspects are included in Chapters 3-7 of this book. 

Siolipin, the hydroxylated ornithine-containing lipid of Streptomyces sioyaensis, was found to specifically inhibit the growth of a strain of Bacillus subtilis when a synthetic culture medium was used. No inhibition was observed when the bacteria were grown on complex medium, as l-histidine and to a lesser degree L-cysteine were able to antagonize the effect of siolipin (55). 

Flavolipin was found to be more active than ornithine-containing lipids in the hemagglutination test the activity was observed at concentrations lower than 1 pg per milliliter (75). 

Ornithine-containing lipid was shown to accelerate the coagulation of blood in a thrombine-fibrinogen system, by using a concentration of 24 pg per ml (55). 

In conclusion, few biological properties have so far been detected for ornithine-containing lipids in spite of their amphiphilic character. 

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Clearly, the next step is the handling of a molecule as a real object with a spatial extension in 3D space. Quite often this is also a mandatory step, because in most cases the 3D structure of a molecule is closely related to a large variety of physical, chemical, and biological properties. In addition, the fundamental importance of an unambiguous definition of stereochemistry becomes obvious, if the 3D structure of a molecule needs to be derived from its chemical graph. The moleofles of stereoisomeric compounds differ in their spatial features and often exhibit quite different properties. Therefore, stereochemical information should always be taken into ac-count if chiral atom centers are present in a chemical structure. 

The major task of chemoinformatics is to find these relationships between the data on the molecular structure and the data on the physical, chemical, or biological properties of the molecules. 

Following the similar structure - similar property principle", high-ranked structures in a similarity search are likely to have similar physicochemical and biological properties to those of the target structure. Accordingly, similarity searches play a pivotal role in database searches related to drug design. Some frequently used distance and similarity measures are illustrated in Section 8.2.1. 

Physical, chemical, and biological properties are related to the 3D structure of a molecule. In essence, the experimental sources of 3D structure information are X-ray crystallography, electron diffraction, or NMR spectroscopy. For compounds without experimental data on their 3D structure, automatic methods for the conversion of the connectivity information into a 3D model are required (see Section 2.9 of this Textbook and Part 2, Chapter 7.1 of the Handbook) [16]. 

The physical, chemical cind biological properties of a molecule often depend critically upo the three-dimensional structures, or conformations, that it can adopt. Conformational analysi is the study of the conformations of a molecule and their influence on its properties. Th development of modem conformational analysis is often attributed to D H R Bcirton, wh showed in 1950 that the reactivity of substituted cyclohexanes wcis influenced by th equatoricil or axial nature of the substituents [Beirton 1950]. An equcilly important reaso for the development of conformatiorml analysis at that time Wcis the introduction c analytic il techniques such as infreired spectroscopy, NMR and X-ray crystaillograph] which actucilly enabled the conformation to be determined. 

Conformational analysis is the study of how conformational factors affect the structure of a molecule and its physical chemical and biological properties... 

An article entitled When Drug Molecules Look in the Mirror in the June 1996 is sue of the Journal of Chemi ca/fdc/cat/on (pp 481-484) describes numerous exam pies of common drugs in which the two enantiomers have different biological properties... 

The biological properties of dioxin include an ability to bind to a protein known as the AH (aromatic hydrocarbon) receptor Dioxin IS not a hydrocarbon but it shares a certain structural property with aromatic hydrocarbons Try constructing molecular models of dioxin and anthracene to see these similarities... 

Many fluorinated, biologically active agents have been developed and successfully used in the treatment of diseases. The biological property of fluorinated organics has been further extended to applications in the agrochemical and pest management fields. 

MISCELLANEOUS FLUORINATED NITROGEN HETEROGYGLIGS Two reviews (1981, 1990) include nitrogen heterocychcs not covered in the present survey (482,483). The 1990 review dealing with four-, five-, and six-membered ring heterocycHc compounds emphasizes biological properties (482). 

KhGH A natural, stmctural variant of hGH called 20-K hGH has been reported to occur in the pituitary as well as in the bloodstream (12,13). This variant, which lacks the 15 amino acid residues from Glu-32 to Gln-46, arises from an alternative splicing of the messenger ribonucleic acid (mRNA) (14). This variant shares many but not all of the biological properties of hGH. 

Truncated Forms. Tmncated forms of hGH have been produced, either through the actions of enzymes or by genetic methods. 2-CAP, generated by the controlled actions of the trypsin, has the first eight residues at the N-terminus of hGH removed. Other tmncated versions of hGH have been produced by modification of the gene before expression in a suitable host. The first 13 residues have been removed to yield a derivative having distinctive biological properties (30). In this latter case the polypeptide chain is not cleaved. 

This group of aluminum carboxylates is characterized mainly by its abiUty to gel vegetable oils and hydrocarbons. Again, monocarboxylate, dicarboxylate, and tricarboxylate salts are important. The chemical, physical, and biological properties of the various types of aluminum stearates have been reviewed (29). Other products include aluminum palmitate and aluminum 2-ethylhexanoate (30). 

The effectiveness of theophylline in the treatment of asthma seems to result from a combination of biological properties which are not clearly understood (63). Detailed discussions of the possible role of xanthines in asthma may be found in references 64—66. 

Ivermectin is the catalytic reduction product of avermectin, a macroHde containing a spiroketal ring system. Two other related antibiotics having significantly different stmctural features and biological properties, moxidectin and milbemycin oxime, were more recentiy introduced into the market. Although these compounds have no antimicrobial activity, they are sometimes referred to as antibiotics because they are derived from fermentation products and have very selective toxicities. They have potent activity against worms or helminths and certain ectoparasites such as mites and ticks. 

In common with the naturally occurring carbapenem thienamycin (2), the introduction of the /n j -6-[l-(R)-hydroxyethyi] group had a profound effect on the biological properties of the penems. This, together with an indication from an early study (93) that, as with other P-lactams, the 5(R)-enantiomer was solely responsible for antibacterial activity, provided impetus for the development of methods for the synthesis of chiral penems. 

Research carried out in a number of laboratories has revealed several members of the penem family having biological properties worthy of further investigation. Some of these compounds are given in Table 2. Extensive studies (135) have also identified BRL 42715 [102209-75-6] (89, R = Na),... 

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