Biological antineoplastic activity

Diazoazoles have found wide application. Among the biological applications is the remarkable antineoplastic activity of several diazoazoles and in particular of 4-diazoimidazole-5-carboxamide. Chemical applications are extensive because of the high reactivity and versatility of the diazo/diazo-nium function. 

This paper presents preliminary biological assay results related to potential antineoplastic activity for select platinum polyamines of Form IV. 

There are several indications, mainly in the patent literature, of possible uses of tetrahydroquinoxalines. Derivatives related in structure to Hetrazan (l-diethylcarbamoyl-4-methylpiperazine) have been prepared as potential drugs for the treatment of filarial infections. Other tetrahydroquinoxalines of type 43 have been screened for antineoplastic activity and bisindolyl derivatives of type 44 have been claimed to have a wide spectrum of biological activity. Tetrahydroquinoxaline phosphates and thiophosphates have been patented as insecticides, and other tetrahydroquinoxalines have been patented for protecting rubber against... 

Carbocyclic analogues of nucleosides are also biologically active. Aristeromycin 51 possesses antimicrobial and neplanocin 52 antineoplastic activity [154]. Abacavir 53, one of the most potent synthetic anti-HIV agents, is a selective inhibitor of HIV-1 and HIV-2 replication [155]. 

Monomethylated derivatives of 2-formylpyridine thiosemicarbazone have been synthesized to define molecular dimensions compatible with antineoplastic activity. These were the thiosemicarbazones of 3-, 4-, 5-, and 6-methylpyridine-2methylated pyridine derivatives were found to be active tumour-inhibitory agents, indicating that substitution of such alkyl groups did not interfere with biological potency. However, introduction of the methyl group in the 6 position of the pyridine ring resulted in a compound with no antineoplastic activity, suggesting an apparent intolerance to substitu-... 

Not all of the above proposed structural requirements have been probed experimentally. However, Sartorelli and coworkers at Yale have elegantly shown that a number of benzoquinones, naphthoquinones, and anthraquinones, meeting the general structure do express antineoplastic activity. Furthermore, the biological activity is indeed... 

Doxorubicin and other anthracyclines, such as daunorubicin, are believed to exhibit their antineoplastic activity through inhibition of topoisomerase II activity. This appears to occur in the absence of significant metal binding by the anthracyclines. Doxorubicin can, however, bind with iron(III) and this results in the formation of a redox-active complex that may cause untoward effects (Myers et al. 1986). Doxorubicin-iron(III) complexes have been shown to oxidatively damage membranes and inactivate protein kinase C, but the biological signficance of this is not well understood (Hannun et al. 1989). 

Teplyokava, G, V., Perelygin, V. V. and Akhimedli, K. M. (1976) Antineoplastic activity of selenium compounds. Proc. Selenium in Biology, Nauchn. Konf. S. Gosanov, Ed., Elm, Baker, USSR, pp. 126-128, 182-192 Se-Te Abstract 34588. 

In early 1987 we proved that the bryostatins were capable of stimulating normal bone marrow progenitor cells to form colonies in vitro and to activate neutrophils (68). Bryostatin 1, e.g., promotes many of the biological effects of GM-CSF and this remarkable activity combined with its antineoplastic activity make it a very attractive clinical candidate. Meanwhile, bryostatins 1 and 2 have found an important role as biochemical probes for unraveling the mechanisms of normal hematopoiesis (69). An important advance here was the observation that bryostatin 1 will stimulate normal erythropoiesis in human bone marrow progenitor assays. Furthermore, bryostatin 1 approximated the stimulatory effects of IL-3 on both murine normal and w/w bone marrow... 

Another interesting and current research field on the in vitro activity of retinoids on breast cancer cell lines focuses on the evaluation of their association with hormones, biological response modifiers or chemotherapeutic drugs, in order to increase their antineoplastic activity. 

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