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AssigneeUniversity of Central Florida Research Foundation, Inc.
InventorOtto Phanstiel
Estimating the term…
Polyamine compounds, method of synthesis and method of use for anti-cancer purposes, and for enhancing the activity of existing anti-cancer drugs are provided. This disclosure has identified certain polyamine motifs that can be attached to toxic agents to facilitate their access to cancer cells as well as polyamine compounds of surprising cytotoxicity and selectivity in killing cancer cells. It includes an illustrative conjugate system with examples of a triamine or a tetraamine appended to a cytotoxic agent. There are five method schemes illustrative of the synthesis of the compounds of the invention. Included is a general strategy to enhance cell uptake by attaching a polyamine vectoring system with an example of a triamine vector attached to an existing anti-cancer drug to improve its chemotherapeutic potency. There is an illustration of using the triamine vector to improve the selectivity of an anthracenylmethyl amine cytotoxic agent (e.g. an anthracenylmethyl-4,4-triamine conjugate outperformed an anthracenylmethyl N-butyl amine derivative). There is an illustration of a synthetic method to attach the polyamine vector onto an existing chemotherapeutic, doxorubicin. This methodology can lead to the synthesis of the polyamine-doxorubicin conjugate. There are illustrations of the synthesis of various alkyl aryl substituted polyamines, a hydroxylated polyamine derivative and a cyclohexyldiamine analogue.
A compound of formula A,
A compound of the formula B,
A compound of formula A,
Dependencies are inferred from the claim text.
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From the US filing history. Foreign family members aren’t listed.
Of an unsaturated carbon skeleton containing at least one six-membered aromatic ring: the six-membered aromatic ring being part of a condensed…
Containing only six-membered rings: anthracenes; Hydrogenated anthracenes
Acyclic or carbocyclic compounds
Term ended 25 Oct 2023 (estimated)
This invention relates to polyamine compounds and more particularly to their use as anticancer agents and their use as a vector for the enhancement of anti-cancer drug activity.
One of the major shortcomings of current cancer therapies is the non-selective delivery of the antineoplastic drug to both targeted tumor cells and healthy cells. Enhanced selectivity of such drugs could diminish their associated toxicity by reducing their uptake by healthy cells. Moreover, selective delivery would increase drug potency by lowering the effective dosage required to kill the affected cell type. Vectored systems, which have enhanced affinity for cancer cells would be an important advance in cancer therapy.
Polyamines are naturally occurring amines, which form polycations in vivo. These stabilize DNA architectures and are cellular growth factors. All cells contain some form of the native polyamines: putrescine, spermidine or spermine. Rapidly dividing cells (such as cancer cells) require large amounts of polyamines, and cells can either biosynthesize or import these essential growth factors. Many tumor cell lines have been shown to have very high levels of polyamines and an active polyamine transporter.
FIG. 1 is a sample conjugate system with two examples, triamine 8 and tetraamine 13.
FIGS. 2A, 2B and 2C (Schemes 1–4) provide general method schemes for the synthesis of the compounds of the invention.
FIG. 3 is a general strategy to enhance cell uptake by polyamine vectoring systems.
Before explaining the disclosed embodiments of the present invention in detail it is to be understood that the invention is not limited in its application to the details of the particular arrangements shown, since the invention is capable of other embodiments. Also, the terminology used herein is for the purpose of description and not of limitation.
It would be useful to discuss the definitions of some words used herein and their applications before discussing the invention, which provides compounds and methods for treating cancer cells without requiring the immune system for their cytotoxicity. For the purposes of this patent application, the term “vector” is used to denote a special chemical message, which is recognized by the polyamine transport system of cells. This special chemical message is a polyamine with the proper or ideal spacing units in between the nitrogen centers. Research has shown that having the proper spacing unit (distance between the nitrogen centers) and having the appropriate number of positive charges (via protonation of the nitrogen centers) is critical for selective cellular uptake.
1) “Vectored systems” relates to polyamine conjugates, which have a polyamine message which is recognized by the polyamine transport system on the surface of cells and have enhanced uptake into cells with highly active polyamine transporters over those which do not, (e.g., CHO vs. CHO-MG cells).