Trail enhancers for the selective killing of cancer cells
The invention is directed to methods of inducing apoptosis, arresting cell cycle, or inhibiting cellular proliferation, or any combination thereof, in a tumor cell, by administration of an effective amount of an N-acyl homoserine lactone analog (AHL), optionally in conjunction with a tumor modulating agent such tumor necrosis factor (TNF) related apoptosis inducing ligand (TRAIL) to the patient. Novel bioactive analogs of an N-acyl homoserine lactone are also provided.
1. A kit comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof:
wherein R is a linear alkyl, alkenyl or alkynyl of about 9 to about 15 carbon atoms having one or more diazirenyl groups, optionally having one or more carbonyl groups on the alkyl, alkenyl or alkynyl groups, and further optionally substituted with azido, hydroxyl, or halo, optionally dissolved in a pharmaceutically acceptable liquid medium, in a container;
the kit optionally further comprising a tumor modulating agent, optionally dissolved in a pharmaceutically acceptable liquid medium, in a second container;
further optionally comprising dosing or storage information, or both.
2. The kit of claim 1 , wherein the compound is of formula (II)
wherein R 1 is a linear alkyl, alkenyl or alkynyl of about 7 to 13 carbon atoms, optionally having one or more of:
a diazirenyl group;
one or more carbonyl groups; or
one or more independently selected azido, hydroxyl, or halo groups.
3. The kit of claim 1 , further comprising a tumor modulating agent that is a TRAIL polypeptide.
4. The kit of claim 1 , wherein the N-acylhomoserine lactone (AHL) analog is selected from the group consisting of: