Synthesis and growth regulatory activity of a prototype member of a new family of aminothiol radioprotectors

Patent metadata

Field	Value
Publication number	US-9458100-B2
Application number	US-201313957188-A
Country	US
Kind code	B2
Filing date	Aug 1, 2013
Priority date	Oct 12, 2012
Publication date	Oct 4, 2016
Grant date	Oct 4, 2016

Abstract

The synthesis, growth inhibition and radioprotective activity of the PrC-210 aminothiol, 3-(methyl-amino)-2-((methylamino)methyl)propane-1-thiol, and its polyamine and thiolated polyamine progenitors are reported. All of the molecules significantly inhibited growth of cultured normal human fibroblasts. The combination of an ROS-scavenging thiol group and a positively charged alkyl-amine backbone provided the most radioprotective aminothiol molecule.

First claim

I claim:

1. A method for protecting a subject from ionizing radiation, the method comprising:
administering systemically to a subject in need thereof an amount of a radioprotector compound comprising a free thiol and a positively-charged backbone, the radioprotector compound comprising a structure according to:

wherein R and R′ are independently selected from H, CH 3 , alkyl, and heteroalkyl;
wherein the amount is effective to protect the subject from ionizing radiation;
wherein systemic administration of the radioprotector compound to the subject is accomplished by intraperitoneal injection or intravenous injection.

2. The method of claim 1 wherein administering systemically to the subject the radioprotector compound does not cause a side effect of nausea, vomiting, hypotension, or fainting in the subject.

3. The method of claim 1 wherein the amount administered is effective to block cell cycle progression at the G1/S cell cycle border.

4. The method of claim 1 wherein the radioprotector compound is sulfurous odor-free.

5. The method of claim 1 wherein the amount administered is effective to inhibit the growth of a cell.

6. The method of claim 1 wherein the amount administered is effective to permit restoration of cell cycle progression.

7. The method of claim 1 wherein the amount administered is effective to bind the positively-charged backbone to a DNA while displaying the free thiol away from the DNA.

8. The method of claim 1 wherein the amount administered is effective to scavenge reactive oxygen species.

9. The method of claim 1 wherein the subject is a mammal.

10. The method of claim 1 wherein the subject is a human.

11. The method of claim 1 wherein the subject is a human comprising a cell exposed to radiation for medical purposes.

12. The method of claim 1 wherein an effective amount of the radioprotector compound is administered systemically at an effective time before or after radiation exposure.

13. The method of claim 1 wherein the systemic administration of the radioprotector compound to the subject is accomplished by intraperitoneal injection.

14. The method of claim 1 wherein the systemic administration of the radioprotector compound to the subject is accomplished by intravenous injection.

Assignees

• Wisconsin Alumni Res Found

Inventors

• Fahl William E

Classifications

• A61K31/145 Primary

  having sulfur, e.g. thiurams (>N—C(S)—S—C(S)—N< and >N—C(S)—S—S—C(S)—N<), Sulfinylamines (—N=SO), Sulfonylamines (—N=SO2) (isothiourea A61K31/155) · CPC title

• A61K31/13 Primary

  Amines {(A61K31/04 takes precedence)} · CPC title

• C07C323/25 Primary

  the carbon skeleton being acyclic and saturated · CPC title