Compound antitumor activity

Biomedical Uses. The molybdate ion is added to total parenteral nutrition protocols and appears to alleviate toxicity of some of the amino acid components in these preparations (see Mineral NUTRIENTS) (97). Molybdenum supplements have been shown to reduce iiitrosarnine-induced mammary carcinomas in rats (50). A number of studies have shown that certain heteropolymolybdates (98) and organometaUic molybdenum compounds (99) have antiviral, including anti-AIDS, and antitumor activity (see Antiviral agents Chemotherapeutics, anticancer). 

Antineoplastic Drugs. Cyclophosphamide (193) produces antineoplastic effects (see Chemotherapeutics, anticancer) via biochemical conversion to a highly reactive phosphoramide mustard (194) it is chiral owing to the tetrahedral phosphoms atom. The therapeutic index of the (3)-(-)-cyclophosphamide [50-18-0] (193) is twice that of the (+)-enantiomer due to increased antitumor activity the enantiomers are equally toxic (139). The effectiveness of the DNA intercalator dmgs adriamycin [57-22-7] (195) and daunomycin [20830-81-3] (196) is affected by changes in stereochemistry within the aglycon portions of these compounds. Inversion of the carbohydrate C-1 stereocenter provides compounds without activity. The carbohydrate C-4 epimer of adriamycin, epimbicin [56420-45-2] is as potent as its parent molecule, but is significandy less toxic (139). 

Miscellaneous. Reductioa of a palladium salt by CO is the basis of a visual test for ambieat carboa moaoxide (227). Palladium compouads are used as photographic seasitizers (228). The low dimensional mixed valeace compouad Csq g3[Pd(S2C2(CN)2)] 0.5H2O behaves as a semimetal at room temperature (229). Palladium compouads isostmctural with poteat platiaum antitumor compounds have poor antitumor activity (230). 

Steroid Antibiotics. The steroid antibiotics are a stmcturaHy diverse class of steroids that have a common biological function, ie, antibacterial, antifungal, antiviral, or antitumor activities. This group of compounds can overlap with other steroid classes Hsted above. Eusidic acid [6990-06-3] (67), helvohc acid [29400-42-8] (68), and cephalosporin [13258-72-5] (69) exemplify a set of antibacterial steroids that contain a prolanostane skeleton with an... 

The antitumor activity displayed by the mitosanes and many synthetic aziridines stems from their ability to act as alkylating agents which chemically modify (crosslink) DNA. For this reason, a large number have been screened for antitumor activity, the mechanism of which has been the subject of considerable research effort <75CJC289l). An excellent account of the broad spectrum of biological properties of a multitude of compounds containing the aziridinyl moiety has been published [Pg.93]

Ferrocenylalkylazoles as a new class of low-toxic compounds with antitumor activity 98MI58. 

Table 5 In vitro antitumor activity (LD50, ng ml values of compounds 1-7, in comparison with some reference compounds used clinically ° ...

When reacted with tetraalkylammonium halides, hydrated [Me2Sn(IV)], [Bu2Sn(IV)]2-",2 [Ph2Sn(IV)]2-", 5 and [EtPhSn(lV)]2-",2 ester derivatives of 2,6-pyridinedicarboxylic acid yield tetraalkylammonium diorganohalogeno(2,6-pyr-idinedicarboxylato)stannates. Both classes of compounds exhibit high in vitro antitumor activity. 

Bis(dicyclohexylammonium) bis(2,6-pyridinedicarboxylato)dibutylstannate is concluded to have sevenfold coordination at the Sn on the basis of its Sn CP/ MAS NMR chemical shift ((5 = —424.9 ppm). The assignment has been corroborated by crystal structure determination of its monohydrate, in which the Sn atom has frflMS-C2SnN04 PBP geometry (Sn-C = 204.0,206.7pm, C-Sn-C = 168.9°). One 2,6-pyiidinedicarboxylato group chelates to the Sn atom (Sn-O = 223.4,226.0 pm Sn-N = 227.9 pm), whereas the other binds through only one carboxyl end (Sn-O = 241.6, 244.1pm). The anhydrous compound displays higher in vitro antitumor activity than those of cisplatin and carboplatin (Table 7). ... 

MS, and in one case XRD. All these compounds display antitumor activity, despite their low solubility in water. ... 

The inhibition doses, ID50, for the compounds and the parent [Bu2Sn(IV)] derivatives are presented in Table 9. These data do not support the hypothesis of Atassi that water-soluble Sn compounds might exhibit higher antitumor activity, at least for the cell lines studied. It should be outlined that the... 

When the antitumor activity of cisplatin was discovered, several research groups started to investigate the possible therapeutic applications of other metal-based, often organometallic, compounds. The organotin(lV) compounds that were first tested were those that were available or easily synthesized, like tri- or diorganotin(rV) halides. 

Table 11 Antitumor activities of organotin(IV) compounds against two types of leukemia cell lines...

Among some 70 new antitumor compounds discovered by H. Umezawa and coworkers, formycin (1966) constituted another important discovery. Produced in conjunction with coformycin, the latter inhibits the activity of adenosine deaminase (1967) and enhances the antitumor activity of formycin. 

A cytotoxic alkaloid has been isolated from the filamentous species Hapalosi-phon forUinalis strain V-3-1. This isolate was made from soil samples collected in the Marshall Islands in 1981. This strain produces the lipophilic compound hapalindole A, which has a broad range of antialgal and antimycotic activity (9). OscUlatoria acutissima strain B-1, isolated from a freshwater pond in Oahu, was found to produce two novel macrolide compounds termed acutiphycin and 20, 21-didehydroacutiphycin. These macrolides show cytotoxicity (KB and NIH/3T3) and antitumor activity (Murine Lewis lung carcinoma) (10). 

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