Structure cytotoxicity and

Segraves NL, Robinson SJ, Garcia D, Said SA, Fu X, Schmitz FJ, Pietraszkiewicz H, Valeriote FA, Crews P (2004) Comparison of Fascaplysin and Related Alkaloids A Study of Structures, Cytotoxicities, and Sources. J Nat Prod 67 783... 

E. and Randaccio, L. (1992) Gold(III) glycyl-L-histidine dipeptide complexes. Preparation and x-ray structures of monomeric and cyclic tetrameric species. Inorganic Chemistry, 31, 1983 (b) Carotti, S., Marcon, G., Marussich, M., Mazzei, T., Messori, L., Mini, E. and Orioli, P. (2000) Cytotoxicity and DNA binding properties... 

Scheme 6 Structure of coralyne derivatives and a substituent in 8-position tested for cytotoxicity and topoisomerase 1 and II poisons...

Haliclonacyclamine E (13) and arenosclerins A (14), B (15), and C (16) have been isolated from the marine sponge Arenosclera brasiliensis, endemic in Brazil. Crude extracts of this sponge displayed potent cytotoxic and antibiotic activities, and were subjected to fractionation by sihca-gel flash chromatography, medium pressure chromatography on a SiOH cyanopropyl-bonded column, and reversed-phase Cis column chromatography to give compounds 13-16 [18]. The structure elucidation was based on spectroscopic analysis, including HRFABMS, COSY, HSQC, HSQC-TOCSY, and HMBC NMR... 

To assess the trapping of biological nucleophiles, the pyrido[l,2-a]indole cyclopropyl quinone methide was generated in the presence of 5 -dGMP. The reaction afforded a mixture of phosphate adducts that could not be separated by reverse-phase chromatography (Fig. 7.16). The 13C-NMR spectrum of the purified mixture shown in Fig. 7.16 reveals that the pyrido [1,2-a] indole was the major product with trace amounts of azepino[l,2-a] indole present. Since the stereoelec-tronic effect favors either product, steric effects must dictate nucleophilic attack at the least hindered cyclopropane carbon to afford the pyrido[l,2-a]indole product. Both adducts were stable with elimination and aromatization not observed. In fact, the pyrido [1,2-a] indole precursor (structure shown in Scheme 7.14) to the pyrido [l,2-a]indole cyclopropyl quinone methide possesses cytotoxic and cytostatic properties not observed with the pyrrolo [1,2-a] indole precursor.47... 

Xing, C. Skibo, E. B. Dorr, R. T. Aziridinyl quinone antitumor agents based on indoles and cyclopent[6]indoles structure-activity relationships for cytotoxicity and antitumor activity. J. Med. Chem. 2001, 44, 3545-3562. 

A more complex structure is that of leinamycin 45 (Scheme 15), a material with potent cytotoxic and antitumor properties, isolated from a Streptomyces sp. A 1,2 dithiolane-3-one ring is spiro fused to a complex macrolactam96 (and references therein). Leinamycin has the remarkable ability to cleave DNA. In brief, leinamycin reacts with a thiol and, after a profound rearrangement, forms an episulfonium ion. This ion alkylates the N7 position of guanosine residues in double stranded DNA an unstable adduct is depurinated by hydrolysis of the glycosidic bond between the alkylated base and a deoxyribose residue. Some structurally less complex l,2-dithiolane-3-one 1-oxides have a similar DNA cleaving ability.97... 

Rauter s group exploited the synthesis of sugar derived bicyclic butenolides ( e.g. 140, Fig. 44),60 which possess cytotoxic and antitumor activities. The key structural feature of such compounds consists of the presence of the a,(3-unsaturated lactone, which allows them to act as Michael acceptors for the addition of enzymes nucleophiles. 

Sovadinova, I., Blaha, L., Janosek, J., Hilscherova, K., Giesy, J.P., Jones, P.D. and Holoubek, I. (2006) Cytotoxicity and aryl hydrocarbon receptor-mediated activity of N-heterocydic polycyclic aromatic hydrocarbons structure-activity relationships. Environmental Toxicology and Chemistry, 25, 1291-1297. 

Nakamura E, Tokuyama H, Yamago S, Shiraki T, Sugiura Y (1996) Biological activity of water-Soluble fullerenes. Structural dependence of DNA cleavage, cytotoxicity, and enzyme inhibitory activities including HIV-Protease inhibition. Bull. Chem. Soc. Jpn. 69 2143-2151. 

C-atoms (19,20). These compounds showed a typical structure-activity correlation between the length of the alkyl side chain and their antitumor activity profile (19). The pharmacokinetic, cytotoxic, and pharmacological properties of N -hexadecyl-ara-C were intensively examined, followed by several studies on the most effective derivative, N -octadecyl-ara-C (NOAC), which is highly... 

Many structure—activity relationship studies of host defense peptides have also focused on LL-37. Importantly, LL-37 has a broad spectrum of activities within the immune system but has also displayed cytotoxic activities that would diminish the therapeutic application of this peptide. Thus, structure—activity studies of LL-37 have focused on this cytotoxicity. A study by Nagaoka et al has demonstrated that the cytotoxic and hemolytic activities of LL-37 may reside within different regions of the peptide. Using an 18-mer... 

The secondary metabolites of the endophytic fungi associated with dicotyledonous plants (dicots) are chemically diverse (Table 1). There is an equal diversity in the activities of these compounds, including antibacterial, antifungal, nematicidal, phytotoxic, cytotoxic, antineoplastic, anti-insectant, anti-herbivory, and a variety of other activities. The compounds isolated, structurally elucidated, and explored biologically in the short time since previous reviews continue to display that same wide array of chemical and biological diversity. 

Acetylnimbandiol was insectidical (EI50 = 21 ppm) when fed to the larvae of II. vlrescens, while the structurally related salannin, which lacks the A-ring ketone (Figure 13), was not (Table VII) (57). Nakanishi (58) has pointed out that natural products with electrophilic moieties tend to be cytotoxic and insect antifeedant. Possibly the growth-Inhibitory activity of the limonoids may also be attributed to a nonspecific electrophilic effect. 

---