Inhibition and treatment of Hepatitis B virus and Flavivirus by Helioxanthin and its analogs

A method of treating a patient for a viral infection selected from the group consisting of Hepatitis B virus, Hepatitis C virus, Yellow Fever, Dengue Virus, Japanese Encephalitis and West Nile virus comprising administering to said patient an effective amount of a compound according to the structure:

• where A is H, OH, OR or forms a 1,3 dioxolane group with B such that A and B are O and are bridged together by a —CH2— group;
• C is H, OH, OR or forms a 1,3 dioxolane group with B such that B and C are O and are bridged together by a —CH2— group;
• B is OH, OR or forms a 1,3 dioxolane group with either A or C;
• R is a C1 to C3 alkyl group or a C1 to C20 acyl group;
• D and E are the same or different and are selected from CH3, CH2OH, CH2OR, CHO, COOH or a pharmaceutically acceptable salt thereof, CH2COOR1 or a keto group or —CH2— group, with the proviso that when D or E is a keto group, the other of D or E is a keto group or a methylene group and D and E are linked together by an —O— group to form a five-membered lactone ring or a dicarboxylic acid anhydride ring;
• R1 is a C1 to C3 alkyl group;
• F and G are H or Br;
• I is H, OH, OR or Br and
• J and K are the same or different and are selected from CH3, CH2OH, CH2OR, CHO, COOH, COO− Na+ or together form a 1,3 dioxolane ring such that J and K are O and are bridged by a —CH2— group.

A pharmaceutical composition for use in treating a virus infection comprising an anti-viral effective amount of at least one compound according to the structure:

• where A is H, OR or forms a 1,3 dioxolane group with B such that A and B are O and are bridged together by a —CH2— group;
• C is H, OH, OR or forms a 1,3 dioxolane group with B such that B and C are O and are bridged together by a —CH2— group;
• B is OH, OR or forms a 1,3 dioxolane group with either A or C;
• R is a C1 to C3 alkyl group, a benzyl group or a C1 to C20 acyl group;
• D and E are the same or different and are selected from CH3, CH2OH, CH2OR, CHO, COOH or a pharmaceutically acceptable salt thereof, CH2COOR1 or a keto group or —CH2— group, with the proviso that when D or E is a keto group, the other of D or E is a keto group or a methylene group and D and E are linked together by an —O— group to form a five-membered lactone ring or a dicarboxylic acid anhydride ring;
• R1 is a C1 to C3 alkyl group;
• F and G are H or Br;
• I is H, OH, OR or Br and
• J and K are the same or different and are selected from CH3, CH2OH, CH2OR, CHO, COOH or a pharmaceutically acceptable salt thereof, or together form a 1,3 dioxolane ring such that J and K are O and are bridged by a —CH2— (methylene) group, optionally in combination with a pharmaceutically acceptable excipient, carrier or additive.

A method of preventing a virus infection in a patient, said virus being selected from the group consisting of Hepatitis B virus, Hepatitis C virus, Yellow Fever virus, Dengue Virus, Japanese Encephalitis virus and West Nile virus comprising administering to said patient in need thereof an effective amount of a compound according to the structure:

• where A is H, OR or forms a 1,3 dioxolane group with B such that A and B are O and are bridged together by a —CH2— group;
• C is H, OH, OR or forms a 1,3 dioxolane group with B such that B and C are O and are bridged together by a —CH2— group;
• B is OH, OR or forms a 1,3 dioxolane group with either A or C;
• R is a C1 to C3 alkyl group, a benzyl group or a C1 to C20 acyl group
• D and E are the same or different and are selected from CH3, CH2OH, CH2OR, CHO, COOH or a pharmaceutically acceptable salt thereof, CH2COOR1 or a keto group or —CH2— group, with the proviso that when D or E is a keto group, the other of D or E is a keto group or a methylene group and D and E are linked together by an —O— group to form a five-membered lactone ring or a dicarboxylic acid anhydride ring;
• R1 is a C1 to C3 alkyl group;
• F and G are H or Br;
• I is H, OH, OR or Br and
• J and K are the same or different and are selected from CH3, CH2OH, CH2OR, CHO, COOH or a pharmaceutically acceptable salt thereof, or together form a 1,3 dioxolane ring such that J and K are O and are bridged by a —CH2— group, optionally in combination with a pharmaceutically acceptable excipient, carrier or additive.

A method of preventing a hepatoma secondary to a Hepatitis B or Hepatitis C virus infection in a patient, said method comprising administering to said patient in need thereof an effective amount of a compound according to the structure:

• where A is H, OR or forms a 1,3 dioxolane group with B such that A and B are O and are bridged together by a —CH2— group;
• C is H, OH, OR or forms a 1,3 dioxolane group with B such that B and C are O and are bridged together by a —CH2— group;
• B is OH, OR or forms a 1,3 dioxolane group with either A or C;
• R is a C1 to C3 alkyl group, a benzyl group or a C1 to C20 acyl group
• D and E are the same or different and are selected from CH3, CH2OH, CH2OR, CHO, COOH or a pharmaceutically acceptable salt thereof, CH2COOR1 or a keto group or —CH2— group, with the proviso that when D or E is a keto group, the other of D or E is a keto group or a methylene group and D and E are linked together by an —O— group to form a five-membered lactone ring or a dicarboxylic acid anhydride ring;
• R1 is a C1 to C3 alkyl group;
• F and G are H or Br;
• I is H, OH, OR or Br and
• J and K are the same or different and are selected from CH3, CH2OH, CH2OR, CHO, COOH or a pharmaceutically acceptable salt thereof, or together form a 1,3 dioxolane ring such that J and K are O and are bridged by a —CH2— group, optionally in combination with a pharmaceutically acceptable excipient, carrier or additive.

A pharmaceutical composition comprising an anti-viral effective amount of at least one compound according to the structure:

• where C, G, F and I are H;
• A is O and B is O such that A and B are bridged together by a —CH2— group to form a 1,3-dioxolane group;
• J is O and K is O such that J and K are bridged together by a —CH2— group to form a 1,3-dioxolane group;
• D is COOH or a pharmaceutically acceptable salt thereof, or a keto group;
• and
• E is CH2OH when D is COOH or its pharmaceutically acceptable salt thereof, or a methylene group when D is a keto group such that D and E are linked together by an —O— group to form a five-membered lactone ring, optionally, in combination with a pharmaceutically acceptable excipient carrier or additive.

A method of treating a patient for a viral infection selected from the group consisting of Hepatitis B virus, Hepatitis C virus, Yellow Fever, Dengue Virus, Japanese Encephalitis, West Nile virus comprising administering to said patient an effective amount of a compound according to the structure:

• where C, G, F and I are H;
• A is O and B is O such that A and B are bridged together by a —CH2— group to form a 1,3-dioxolane group;
• J is O and K is O such that J and K are bridged together by a —CH2— group to form a 1,3-dioxolane group;
• D is COOH or a pharmaceutically acceptable salt thereof, or a keto group;
• and
• E is CH2OH when D is COOH or its pharmaceutically acceptable salt thereof, or a methylene group when D is a keto group such that D and E are linked together by an —O— group to form a five-membered lactone ring, optionally, in combination with a pharmaceutically acceptable excipient carrier or additive.

A method of preventing a virus infection in a patient, said virus being selected from the group consisting of Hepatitis B virus, Hepatitis C virus, Yellow Fever virus, Dengue Virus, Japanese Encephalitis virus and West Nile virus comprising administering to said patient in need thereof an effective amount of a compound according to the structure:

• where C, G, F and I are H;
• A is O and B is O such that A and B are bridged together by a —CH2— group to form a 1,3-dioxolane group;
• J is O and K is O such that J and K are bridged together by a —CH2— group to form a 1,3-dioxolane group;
• D is COOH or a pharmaceutically acceptable salt thereof, or a keto group;
• and
• E is CH2OH when D is COOH or its pharmaceutically acceptable salt thereof, or a methylene group when D is a keto group such that D and E are linked together by an —O— group to form a five-membered lactone ring, optionally, in combination with a pharmaceutically acceptable excipient carrier or additive.

A method of preventing a hepatoma secondary to a Hepatitis B or Hepatitis C virus infection in a patient, said method comprising administering to said patient in need thereof an effective amount of a compound according to the structure:

• where C, G, F and I are H;
• A is O and B is O such that A and B are bridged together by a —CH2— group to form a 1,3-dioxolane group;
• J is O and K is O such that J and K are bridged together by a —CH2— group to form a 1,3-dioxolane group;
• D is COOH or a pharmaceutically acceptable salt thereof, or a keto group;
• and
• E is CH2OH when D is COOH or its pharmaceutically acceptable salt thereof, or a methylene group when D is a keto group such that D and E are linked together by an —O— group to form a five-membered lactone ring, optionally, in combination with a pharmaceutically acceptable excipient carrier or additive.