Uses of nordihydroguaiaretic acid (NDGA) and derivatives thereof in preventing transmission of sexually transmitted diseases

Abstract

Provided herein are methods for inhibiting proliferation of a microbe associated with a sexually transmitted disease (STD) or infection and for preventing transmission of one or more sexually transmitted diseases in a subject at-risk for acquiring the same, including an HIV positive subject at risk for acquiring another sexually transmitted disease. The methods comprise contacting a microbe or cell thereof associated with the STD or administering to the subject nordihydroguaiaretic acid or a derivative or analog thereof. In HIV positive at-risk subjects one or more anti-retroviral drugs are co-administered.

1 . A method for inhibiting proliferation of a microbe associated with a sexually transmitted disease or infection, comprising:
 contacting the microbe or a microbial cell thereof with an amount of one or more microbicidal compounds effective to inhibit an activity required for proliferation thereof, said compounds having a structural formula   
       
         
           
           
               
               
           
         
       
       wherein R 1 -R 4  are independently H, C 1 -C 2 alkyl, C(═O)(C 1 -C 2 alkyl), —C(═O)CH 2 NH 2 , —C(═O)CH 2 N(H)(C 1 -C 2 alkyl) 2 , or —C 1 -C 2 alkyl-N-piperidinyl, or a pharmacologically effective salt or hydrate thereof. 
     
     
         2 . The method of  claim 1 , wherein R 1 -R 4  are independently H, CH 3 , —C(═O)CH 2 N(H)(CH 3 ) 2 , —C(═O)CH 2 N(H)(CH 3 ) 2 .Cl, or —CH 2 CH 2 —N-piperidinyl. 
     
     
         3 . The method of  claim 2 , wherein the microbicidal compound(s) is one or more of nordihydroguaiaretic acid (NDGA), tetra-O-methyl-nordihydroguaiaretic acid (M 4 N), tetra-O—(N,N-dimethyl)glycyl-nordihydroguaiaretic acid (G 4 N) or the hydrochloride salt thereof, 3′-O-methyl nordihydroguaiaretic acid (Mal.4), or tetra-O—(N-ethyl)piperidinyl-nordihydroguaiaretic acid (P 4 N). 
     
     
         4 . The method of  claim 3 , wherein the microbe is a human immunodeficiency virus (HIV), a herpes simplex virus (HSV), a human papilloma virus (HPV), a hepatitis virus, a Molluscipox virus,  Haemophilus ducreyi, Chlamydia trachomatis, Neisseria gonorrhoeae, Treponema pallidum, Sarcoptes scabiei  or a crab louse. 
     
     
         5 . A method for preventing transmission of one or more sexually transmitted diseases in a subject at-risk for acquiring the same, comprising:
 administering one or more of a microbicidal compound to the subject, said compound(s) having a structural formula   
       
         
           
           
               
               
           
         
       
       wherein R 1 -R 4  are independently H, C 1 -C 2 alkyl, C(═O)(C 1 -C 2 alkyl), —C(═O)CH 2 NH 2 , —C(═O)CH 2 N(H)(C 1 -C 2 alkyl) 2 , or —C 1 -C 2 alkyl-N-piperidinyl, or a pharmacologically effective salt or hydrate thereof. 
     
     
         6 . The method of  claim 5 , wherein R 1 -R 4  are independently H, CH 3 , —C(═O)CH 2 N(H)(CH 3 ) 2 , —C(═O)CH 2 N(H)(CH 3 ) 2 .Cl, or —CH 2 CH 2 —N-piperidinyl. 
     
     
         7 . The method of  claim 6 , wherein the microbicidal compound(s) is one or more of nordihydroguaiaretic acid (NDGA), tetra-O-methyl-nordihydroguaiaretic acid (M 4 N), tetra-O—(N,N-dimethyl)glycyl-nordihydroguaiaretic acid (G 4 N) or the hydrochloride salt thereof, 3′-O-methyl nordihydroguaiaretic acid (Mal.4), or tetra-O—(N-ethyl)piperidinyl-nordihydroguaiaretic acid (P 4 N). 
     
     
         8 . The method of  claim 5 , wherein the at-risk subject already has a sexually transmitted disease, the method further comprising:
 administering one or more other anti-STD drugs thereto.   
     
     
         9 . The method of  claim 8 , wherein the at-risk subject has HIV and the other anti-STD(s) drug comprises one or more anti-retroviral drugs. 
     
     
         10 . The method of  claim 5 , wherein the microbicidal compound(s) is formulated as a topical pharmaceutical composition comprising the compounds and a pharmaceutically acceptable carrier suitable for topical administration. 
     
     
         11 . The method of  claim 5 , wherein the microbicidal compound(s) is administered vaginally, rectally or bucally. 
     
     
         12 . The method of  claim 5 , wherein the microbicidal compound(s) is administered before or after sexual intercourse. 
     
     
         13 . The method of  claim 5 , wherein the sexually transmitted disease is HIV, genital warts, herpes, chancroid, chlamydia, crab lice, gonorrhea, hepatitis, lympogranuloma venereum, molluscum contagiosum, nongonococcal urethritis, pelvic inflammatory disease, scabies, syphilis, or vaginitis. 
     
     
         14 . A method for preventing transmission of one or more sexually transmitted diseases in an HIV positive subject at-risk for acquiring the same, comprising:
 co-administering one or more of a microbicidal compound to the subject, said compound(s) having a structural formula   
       
         
           
           
               
               
           
         
       
       wherein R 1 -R 4  are independently H, C 1 -C 2 alkyl, C(═O)(C 1 -C 2 alkyl), —C(═O)CH 2 NH 2 , —C(═O)CH 2 N(H)(C 1 -C 2 alkyl) 2 , or —C 1 -C 2 alkyl-N-piperidinyl, or a pharmacologically effective salt or hydrate thereof and one or more anti-retroviral drugs. 
     
     
         15 . The method of  claim 14 , wherein R 1 -R 4  are independently H, CH 3 , —C(═O)CH 2 N(H)(CH 3 ) 2 , —C(═O)CH 2 N(H)(CH 3 ) 2 .Cl, or —CH 2 CH 2 —N-piperidinyl. 
     
     
         16 . The method of  claim 15 , wherein the microbicidal compound(s) is one or more of nordihydroguaiaretic acid (NDGA), tetra-O-methyl-nordihydroguaiaretic acid (M 4 N), tetra-O—(N,N-dimethyl)glycyl-nordihydroguaiaretic acid (G 4 N) or the hydrochloride salt thereof, 3′-O-methyl nordihydroguaiaretic acid (Mal.4), or tetra-O—(N-ethyl)piperidinyl-nordihydroguaiaretic acid (P 4 N). 
     
     
         17 . The method of  claim 14 , wherein the microbicidal compound(s) is formulated as a topical pharmaceutical composition comprising the compounds and a pharmaceutically acceptable carrier suitable for topical administration. 
     
     
         18 . The method of  claim 14 , wherein the microbicidal compound(s) is administered vaginally, rectally or bucally. 
     
     
         19 . The method of  claim 14 , wherein the microbicidal compound(s) is administered before or after sexual intercourse. 
     
     
         20 . The method of  claim 14 , wherein the sexually transmitted disease is HIV, genital warts, herpes, chancroid, chlamydia, crab lice, gonorrhea, hepatitis, lympogranuloma venereum, molluscum contagiosum, nongonococcal urethritis, pelvic inflammatory disease, scabies, syphilis, or vaginitis.