The present invention relates to the inhibition of cancer cell growth, proliferation, and metastasis by contacting cells with an N,N'-dibenzyl .alpha.,.omega.-diaminoalkane, a derivative of naturally-occurring putrescine. More specifically, the present invention relates to the treatment of cancer in humans by administration of a cancer cell growth-inhibiting amount of an N,N'-dibenzyl .alpha.,.omega.-diaminoalkane to a human cancer patient.
Cytotoxic polyamine analogues are provided that are useful for treating diseases where it is desired to inhibit cell growth and/or proliferation, for example cancer and post-angioplasty injury.
Methods for modulating macrophage proliferation in an individual afflicted with or at risk for a macrophage-associated disease are provided. The methods employ a polyamine analog, or salt or protected derivative thereof. Macrophage proliferation has been implicated in a number of serious disorders, including AIDS (HIV)-associated dementia, AIDS-associated non-Hodgkin's lymphoma, and Alzheimer's disease. The invention also provides methods for aiding diagnosis and monitoring therapy of a macrophage-associated non-HIV associated dementia, especially Alzheimer's disease. The invention also provides methods of delaying development of macrophage-associated non-HIV associated dementias, including Alzheimer's disease, which entail administration of an agent which modulates macrophage proliferation.
Polyamine effectors are administered locally to provide protection against the adverse side-effects of chemotherapy or radiation therapy, such as alopecia, mucositis and dermatitis. Pharmaceutical preparations comprising one or more polyamine effectors formulated for topical or local delivery to epithelial or mucosal cells are disclosed. Methods of administering the pharmaceutical preparations are also disclosed.
Conformationally restricted polyamine compounds useful in treatment of cancer and other diseases marked by abnormal cell proliferation are disclosed. Improved methods of synthesizing such compounds are also disclosed. In one method of the invention, a carbene-bearing or carbene equivalent-bearing compound is reacted with the double bond of an alkene compound to form a cyclopropyl ring as the first step in the synthesis.
Novel conformationally restricted polyamine analogs are provided, as well as compositions comprising these novel polyamine analogs. Methods of using the novel polyamine analogs in treatment of diseases such as cancer are also provided. Also provided is a method of delivering these analogs specifically to tumor cells by covalently attaching polyamine analogs to, porphyrin compounds, along with novel polyamine-porphyrin covalent conjugates.
