Cytotoxic properties

Several thiadiazolo-triazoles 43 have been synthesized that show antifungal and cytotoxic properties. hiadiazoles 45 were prepared from hydrazones 44 by treating them neat with thionyl chloride at room temperatures. The thiadiazoles were formed regio-selectively on the methyl group of the hydrazone. 

Target tissue sections from animals sacrificed at 8 hr and later after dosing showed the presence of microspheres in the extravas-cular interstitial tissue. Changes in red blood cells and damage to other cellular components suggest that the cytotoxic properties of adriamycin have been retained. The microspheres appeared to still be intact for up to 72 hr. 

Messori, L, Abbate, F., Marcon, G., Orioli, P., Fontani, M., Mini, E., Mazzei, T., Carotti, S., O Connell, T. and Zanello, P. (2000) Gold(lll) complexes as potential antitumor agents solution chemistry and cytotoxic properties of some selected gold(III) compounds. Journal of Medicinal Chemistry, 43, 3541. 

Berners-Price, S., Mirabelli, C.K. and Johnson, R.K. (1986) In vivo antitumor activity and in vitro cytotoxic properties of bis[l,2-bis(diphenylphosphino)ethane] gold(I) chloride. Cancer Research, 46, 5486-5493. 

There are numerous examples of intramolecular Heck reactions,151 such as in Entries 10 to 14. Entry 11 is part of a synthesis of the antitumor agent camptothecin. The Heck reaction gives an 11 1 endocyclic-exocyclic mixture. Entries 12-14 are also steps in syntheses of biologically active substances. Entry 12 is part of a synthesis of maritidine, an alkaloid with cytotoxic properties the reaction in Entry 13 is on a route to galanthamine, a potential candidate for treatment of Alzheimer s disease and Entry 14 is a key step in the synthesis of a potent antitumor agent isolated from a marine organism. 

KhdourO. SkiboE. B. Chemistry of pyrrolo[l,2-a]indole- andpyrido[l,2-a]indole-based quinone methides. Mechanistic explanations for differences in cytostatic/cytotoxic properties. J. Org. Chem. 2007, 72, 8636-8647. 

Pro-Oxidant and Cytotoxic Properties of the Degradation Products of Carotenoids.329... 

PRO-OXIDANT AND CYTOTOXIC PROPERTIES OF THE DEGRADATION PRODUCTS OF CAROTENOIDS... 

Protein toxin possessing cytotoxic properties in vivo... 

Figure 21.13 Sulfo-SMCC may be used to activate antibody molecules for coupling to thiolated toxin components. An intact A-B toxin molecule can be modified to contain sulfhydryls by treatment with 2-iminothiolane. Thiolation with this reagent retains the cytotoxic properties of the toxin while generating a sulfhydryl for conjugation. Reaction of the thiolated toxin with the maleimide-activated antibody creates the immunotoxin through thioether bond formation.

Dimeric structures are possible as exemplified by the leptosins, from a strain of Leptosphaeria (a fungus isolated from the marine alga Sargassum tortile). Some of these, e.g. leptosin A 11, may have up to 4 sulfur atoms across the diketopiperazine ring system.23 Various leptosins have antitumor and cytotoxic properties. 

The products formed during lipid peroxidation include unsaturated aldehydes, such as 4-hydroxynonenal. Their quantification is of great interest because of their extremely reactive and cytotoxic properties. This extreme reactivity and metabolic conversion, however, may make them unsuitable as test analytes for in vivo antioxidant activity studies except at high levels of oxidative stress. Furthermore, simple chemical tests such as the TBARS (thiobarbituric acid reactive substances) and LPO-586 (colorimetric... 

SH-SY5Y neuroblastoma, cisplatin-sensitive A2780 and cispla-tin-resistant A2780cis human ovarian cancer cells was observed, but upon irradiation 7 strongly reduced the viability of the cancer cells (Fig. 8). In the A2780 cell line, the complex was 80x more toxic than cisplatin under identical conditions, and ca. 15 x more effective against the cisplatin-resistant A2780cis cell line (33). The trans diazido-Pt(IV) complex therefore has remarkable cytotoxic properties. 

Tenidis, K., Waldner, M., Bemhagen.J., Fischle, W., Bergmann, M., Weber, M., Merkle, M. L., Voelter, W., Brunner, H., and Kapumiotu, A. (2000). Identification of a penta- and hexapeptide of islet amyloid polypeptide (IAPP) with amyloidogenic and cytotoxic properties. / Mol. Biol. 295, 1055-1071. 

Currently available information suggests that the shape of nanomaterials can affect their toxicity in two ways. First, the shape has an effect on the rate of its cellular uptake and second, it can affect the extent of nanomaterial aggregation, altering its cytotoxic properties. A recent in vitro toxicity study showed spherical nanomaterials to be more toxic than rods [120]. It was also shown to be more difficult for elliptical nanomaterials to penetrate the skin layer than spherical nanomaterials [121]. 

From the fore gut of Laccophilus minutus, a Bacillus pumilus strain was isolated which produced maculosin, the diketopiperazine formed from proline and tyrosine [103] 24, phenyl malonate 25, N-acetylphenylalanine 26, N-acetyl-tryptophane 27 and 3,4-dihydroxybenzoic acid [ 103]. Maculosin which has also been isolated from several microorganisms and sponges shows phytotoxic and cytotoxic properties [103], 3,4-dihydroxybenzoic acid shows antioxidant properties and was already found in pygidial defensive glands of several dytis-cid beetles. 

Two clinical trials of the effects of feverfew in migraine have shown beneficial effects by feverfew but no clinical benefit could be demonstrated for arthritis. There have been suggestions that platelets and neutrophils may play a role in migraine and arthritis respectively, although no study has clearly established a link between any in vitro effects of feverfew and possible clinical benefits. Few side-effects have been noted and although the components of feverfew have been shown to have cytotoxic properties under some experimental conditions, the relevance of this to the clinical situation is not clear. 

The health impairing and toxic elfects of oxidation of lipids are due to loss of vitamins, polyenoic fatty acids, and other nutritionally essential components formation of radicals, hydroperoxides, aldehydes, epoxides, dimers, and polymers and participation of the secondary products in initiation of oxidation of proteins and in the Maillard reaction. Dilferent oxysterols have been shown in vitro and in vivo to have atherogenic, mutagenic, carcinogenic, angiotoxic, and cytotoxic properties, as well as the ability to inhibit cholesterol synthesis (Tai et ah, 1999 Wpsowicz, 2002). 

The methylene chloride soluble portion of a methanol extract from the wood of Eury-coma longifolia shows strong cytotoxic properties. One of the active constituents, longi-lene peroxide (77) (P2i, 0—0 = 1.472 A, Figure 31), was isolated in a 0.0003% yield. The characteristic horse-shoe-like arrangement, which is observed in the crystal structure of squalene derivative 77, has been associated with its biological activity ... 

The total synthesis of litseaverticillols D, F and G (172 and 173), which are natural products with anti-HIV activity, was achieved recently via a singlet oxygen initiated cascade proposed to be biomimetic (Scheme 64). Finally, allylic alcohols 174a and 174b (Scheme 64) were isolated in a 4/1 ratio via a stereoselective singlet oxygen ene reaction. Stereoisomer 174a is an intermediate in the synthetic route of staurosporine, which is a bioactive alkaloid with hypotensive, antimicrobial and cell cytotoxic properties. 

These examples represent only a fraction of the endoperoxide-containing marine metabolites and the number of peroxide metabolites discovered with cytotoxic properties is likely to continue to expand. 

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