Antileukemic activity/agents

Antiknock agent Antiknock index Antileishmanial agent Antileukemic activity Antdon... 

Bis(thiosemicarbazones) [89-97] and AT-heterocyclic thiosemicarbazones comprise two interesting series of experimental chemotherapeutic agents. 2-formylpyridine thiosemicarbazone, the first of the latter series to be examined for biological activity, showed mild antileukemic activity against 1-1210 tumor in mice [98]. However, it was found to be toxic at the therapeutic dose levels which led to synthesis of other aromatic and heterocyclic thiosemicarbazones as potential agents [80, 99, 100]. However, the only active anticancer compounds besides glyoxal bis(thiosemicarbazones) were the iV-heterocyclic thiosemicarbazones [101], 2 formyl-3-hydroxypyridine thiosemicarbazone [102] and... 

Decitabine (1) is a hypomethylating agent that exhibits potent antileukemic activity by inducing epigenetic changes in chromatin or reactivating tumor suppressor genes. It is administered intravenously at 15 mg/m2 over 3 h every 8 h for 3 consecutive days. The frequency of this administration is every 6 weeks. 

The alkaloid colchicine (FI) isolated from the medicinal plant Colchicum autumnale L. (Liliaceae family) still is used to treat gout and familial Mediterranean fever. FI and thiocolchicine (F2) (SCH3 rather than OCH3 at C-10), which is more stable and more potent but slightly more toxic, are mitotic inhibitors that inhibit polymerization of tubulin (69). Although they show antileukemic activity, they are too toxic to use as anticancer agents, which prompts the synthesis of new, less toxic analogs. 

In 1953, it was reported that gninea pig serum had antileukemic activity, and L-asparaginase (L-asp) was identified as the source of this activity. Fifteen (15) years later, the enzyme was introduced into cancer chemotherapy in an effort to exploit a distinct, qualitative difference between normal and malignant cells. It remains a standard agent for treating lymphocytic leukemia. 

Chang, P Lee, K.H Shingu, T Ilirayama, T Hall, I.H. Antitumor Agents 50. Morindaparvin-A, a new antileukemic anthraquinone, and alizarin 1-methyl ether from Morinda parvifolia, and the antileukemic activity of the related derivatives. J. Nat. Prod. 1982,45(2), 206. 

Representatives of another important class of plant-derived semisynthetic compounds are the camptothecin (27) derivatives, irinotecan (28) and topotecan (29). Camptothecin (27) was originally discovered as an antileukemic agent in a mouse model when isolated from Camptotheca acuminata Decne. Compounds (28) and (29) are both employed in cancer chemotherapy. These substances are important mechanistically because of their activity against the enzyme, topoisomerase I. These compounds were designed to address efficacy and toxicity concerns with the parent compound, camptothecin, and its sodium salt. ... 

From another Dysidea sponge species, Dysidea avara, the sesquiterpenes avarol, Fig. (9) and avarone, Fig. (10), which show a wide variety of biological activities, were first isolated. Both compounds are potent antileukemic agents in vitro and in vivo. They were determined to be neither direct mutagens nor premutagens, and they displayed antimutagenic activity... 

Theonelladins C 214 and D 215 and niphatesine C 216 are members of a rapidly growing dass of 3-substituted pyridine alkaloids that are known to display important biological activities (Scheme 12.30) [107]. For instance, theonelladins C and D have shown antileukemic and antineoplastic properties while niphatesine C is a known antileukemic agent. 

Nitidine and garonine are known as potential anti-tumour, antileukemic, and antiviral agents [9,52,98]. Some synthetic 12-alkoxyderivatives of 2,3,8,9-tetramethoxy QBA are potent in vitro inhibitors of the growth of P388 cells [144]. Nitidine, isolated firom Kenyan Toddalia aculeata Pers. (synonym T. asiatica (L.) Lamk.) has shown antimalarial activity [145]. Nitidine and fagaronine have been foimd to inhibit HTV reverse transcriptase [146]. 

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