Method for Immunomodulation of using Aza-podophyllotoxin derivatives

Abstract

Disclosed is the novel use of some Aza-podophyllotoxin derivatives (AZPs) for modulation of the immune system (immunomodulation), including a method for modulating an immune response comprising administering to a subject an effective amount of at least one Aza-podophyllotoxin derivative of general formula wherein A-ring is selected from the group consisting of 1,3-dioxolane, cyclopentane, 1,4-dioxane, one methoxy, two methoxys, and ethyl; and wherein E-ring is selected from the group consisting of dimethoxyanisole, veratrol, anisole, benzene, syringol, bromobenzene, chlorobenzene, 1,2-dichlorobenzene, 2,3-dimethoxybenzene, 3,4,5-trimethoxybenzene.

What is claimed: 
     
         1 . A method for modulating an immune response comprising:
 administering to a subject an effective amount of at least one Aza-podophyllotoxin derivative of general formula:   
       
         
           
           
               
               
           
         
         wherein A-ring is selected from the group consisting of 1,3-dioxolane, cyclopentane, 1,4-dioxane, one methoxy, two methoxys, and ethyl; and wherein E-ring is selected from the group consisting of dimethoxyanisole, veratrol, anisole, benzene, syringol, bromobenzene, chlorobenzene, 1,2-dichlorobenzene, 2,3-dimethoxybenzene, 3,4,5-trimethoxybenzene. 
       
     
     
         2 . The method according to  claim 1 , wherein the subject suffers from at least one ailment, such ailment selected from the group consisting of:
 fever, neutropenia, trauma, infection, sepsis, stress, neoplastia, cancer, allergy, and inflammation.   
     
     
         3 . The method according to  claim 1 , wherein the at least one Aza-podophyllotoxin derivative is selected from the group consisting of AP102, AP103, AP104, AP205, AP311, and AP 312. 
     
     
         4 . The method according to  claim 1 , wherein the at least one Aza-podophyllotoxin derivative is AP205, and wherein the AP205 is administered to the subject in a dose of 10 μM. 
     
     
         5 . The method according to  claim 1 , wherein the at least one Aza-podophyllotoxin derivative is AP104, and wherein the AP104 is administered to the subject in a dose of 10 μM. 
     
     
         6 . The method according to  claim 1 , wherein the at least one Aza-podophyllotoxin derivative is AP311, and wherein the AP311 is administered to the subject in a dose of 10 μM. 
     
     
         7 . The method according to  claim 1 , wherein the at least one Aza-podophyllotoxin derivative is AP312, and wherein the AP312 is administered to the subject in a dose of 10 μM. 
     
     
         8 . The method according to  claim 1 , wherein the at least one Aza-podophyllotoxin derivative is AP102, and wherein the AP102 is administered to the subject in a dose of 10 μM. 
     
     
         9 . The method according to  claim 1 , wherein the at least one Aza-podophyllotoxin derivative is AP103, and wherein the AP103 is administered to the subject in a dose of 10 μM. 
     
     
         10 . A method of treating an ailment comprising:
 Identifying a subject suffering from an ailment selected from the group consisting of:   fever, neutropenia, trauma, infection, sepsis, stress, neoplastia, cancer, allergy, and inflammation; and   administering to the subject an effective amount of at least one Aza-podophyllotoxin derivative of general formula:   
       
         
           
           
               
               
           
         
         wherein A-ring is selected from the group consisting of 1,3-dioxolane, cyclopentane, 1,4-dioxane, one methoxy, two methoxys, and ethyl; and wherein E-ring is selected from the group consisting of dimethoxyanisole, veratrol, anisole, benzene, syringol, bromobenzene, chlorobenzene, 1,2-dichlorobenzene, 2,3-dimethoxybenzene, 3,4,5-trimethoxybenzene. 
       
     
     
         11 . The method according to  claim 10 , wherein the at least one Aza-podophyllotoxin derivative is selected from the group consisting of AP102, AP103, AP104, AP205, AP311, and AP312. 
     
     
         12 . The method according to  claim 10 , wherein the at least one Aza-podophyllotoxin derivative is AP205, and wherein the AP205 is administered to the subject in a dose of 10 μM. 
     
     
         13 . The method according to  claim 10 , wherein the at least one Aza-podophyllotoxin derivative is AP104, and wherein the AP104 is administered to the subject in a dose of 10 μM. 
     
     
         14 . The method according to  claim 10 , wherein the at least one Aza-podophyllotoxin derivative is AP311, and wherein the AP311 is administered to the subject in a dose of 10 μM. 
     
     
         15 . The method according to  claim 10 , wherein the at least one Aza-podophyllotoxin derivative is AP312, and wherein the AP312 is administered to the subject in a dose of 10 μM. 
     
     
         16 . The method according to  claim 10 , wherein the at least one Aza-podophyllotoxin derivative is AP102, and wherein the AP102 is administered to the subject in a dose of 10 μM. 
     
     
         17 . The method according to  claim 10 , wherein the at least one Aza-podophyllotoxin derivative is AP103, and wherein the AP103 is administered to the subject in a dose of 10 μM. 
     
     
         18 . A method for stimulating the production of a cytokine comprising:
 Selecting a cytokine from the group consisting of:   IL-6, GCSF, IL-10, IL-2p70, IL-23, and IFN-gamma; and   administering to a splenocyte at least one Aza-podophyllotoxin derivative of general formula:   
       
         
           
           
               
               
           
         
         wherein A-ring is selected from the group consisting of 1,3-dioxolane, cyclopentane, 1,4-dioxane, one methoxy, two methoxys, and ethyl; and wherein E-ring is selected from the group consisting of dimethoxyanisole, veratrol, anisole, benzene, syringol, bromobenzene, chlorobenzene, 1,2-dichlorobenzene, 2,3-dimethoxybenzene, 3,4,5-trimethoxybenzene. 
       
     
     
         19 . The method according to  claim 18 , wherein the at least one Aza-podophyllotoxin derivative is selected from the group consisting of AP102, AP103, AP104, AP205, AP311, and AP 312. 
     
     
         20 . The method according to  claim 18 , wherein the at least one Aza-podophyllotoxin derivative is AP205, and wherein the AP205 is administered to the splenocyte in a dose of 10 μM. 
     
     
         21 . The method according to  claim 18 , wherein the at least one Aza-podophyllotoxin derivative is AP104, and wherein the AP104 is administered to the splenocyte in a dose of 10 μM.