Compounds for use in the treatment of cancer

1. A pharmaceutical composition comprising a first compound of Formula I or a physiologically acceptable salt thereof, and a cyto-protective amount of a manganese chelate of N,N′-dipyridoxyl ethylenediamine-N,N′-diacetic acid (MnPLED):

wherein

X is CH or N,

each R 1 independently is hydrogen or —CH 2 COR 5 ;

R 5 is hydroxy, optionally hydroxylated alkoxy, amino or alkylamido;

each R 2 independently is a group ZYR 6 ;

Z is a bond, CO, or a C 1-3 alkylene or oxoalkylene group optionally substituted by a group R 7 ;

Y is a bond, an oxygen atom or a group NR 6 ;

R 6 is a hydrogen atom, COOR 8 , an alkyl, alkenyl, cycloalkyl, aryl or aralkyl group optionally substituted by one or more groups selected from COOR 8 , CONR 8 2 , NR 8 2 , OR 8 , ═NR 8 , ═O, OP(O)(OR 8 )R 7 and OSO 3 M;

R 7 is hydroxy, an optionally hydroxylated, optionally alkoxylated alkyl or aminoalkyl group;

R 8 is a hydrogen atom or an optionally hydroxylated, optionally alkoxylated alkyl group;

M is a hydrogen atom or one equivalent of a physiologically tolerable cation;

R 3 is a C 1-8 alkylene group, a 1,2-cykloalkylene group, or a 1,2-arylene group, optionally substituted with R 7 ; and

each R 4 independently is hydrogen or C 1-3 alkyl.

2. The pharmaceutical composition of claim 1 , wherein in the first compound of Formula I:

R 5 is hydroxy, C 1-8 alkoxy, ethylene glycol, glycerol, amino or C 1-8 alkylamido;

Z is a bond or a group selected from CH 2 , (CH 2 ) 2 , CO, CH 2 CO, CH 2 CH 2 CO and CH 2 COCH 2 ;

Y is a bond;

R 6 is a mono- or poly(hydroxy or alkoxylated) alkyl group or a group of the formula OP(O) (OR 8 )R 7 ; and

R 7 is hydroxy, or an unsubstituted alkyl or aminoalkyl group.

3. The pharmaceutical composition of claim 1 , wherein in the first compound of Formula I: R 3 is ethylene and each group R 1 represents —CH 2 COR 5 in which R 5 is hydroxy.

4. The pharmaceutical composition of claim 1 , wherein the first compound is N,N′-dipyridoxyl ethylenediamine-N,N′-diacetic acid (PLED).

5. The pharmaceutical composition of claim 1 , wherein the first compound is N,N′-bis-(pyridoxal-5-phosphate)-ethylenediamine-N,N′-diacetic acid (DPDP).

6. The pharmaceutical composition of claim 5 , wherein the molar ratio of the MnPLED to DPDP is in the range of 1/100 to 99/100.

7. The pharmaceutical composition of claim 1 , wherein the molar ratio of the MnPLED to the first compound is in the range of 1/100 to 99/100.

8. A kit comprising a preparation of a first active ingredient of Formula I, a preparation of a manganese chelate of N,N′-dipyridoxyl ethylenediamine-N,N′-diacetic acid (MnPLED), and optionally instructions for the simultaneous, sequential or separate administration of the preparations to a patient in need thereof:

or a physiologically acceptable salt thereof, wherein

X is CH or N,

each R 1 independently is hydrogen or —CH 2 COR 5 ;

R 5 is hydroxy, optionally hydroxylated alkoxy, amino or alkylamido;

each R 2 independently is a group ZYR 6 ;

Z is a bond, CO, or a C 1-3 alkylene or oxoalkylene group optionally substituted by a group R 7 ;

Y is a bond, an oxygen atom or a group NR 6 ;

R 6 is a hydrogen atom, COOR 8 , an alkyl, alkenyl, cycloalkyl, aryl or aralkyl group optionally substituted by one or more groups selected from COOR 8 , CONR 8 2 , NR 8 2 , OR 8 , ═NR 8 , ═O, OP(O)(OR 8 )R 7 and OSO 3 M;

R 7 is hydroxy, an optionally hydroxylated, optionally alkoxylated alkyl or aminoalkyl group;

R 8 is a hydrogen atom or an optionally hydroxylated, optionally alkoxylated alkyl group;

M is a hydrogen atom or one equivalent of a physiologically tolerable cation;

R 3 is a C 1-8 alkylene group, a 1,2-cykloalkylene group, or a 1,2-arylene group, optionally substituted with R 7 ; and

each R 4 independently is hydrogen or C 1-3 alkyl.

9. The kit of claim 8 , wherein in the first compound of Formula I:

R 5 is hydroxy, C 1-8 alkoxy, ethylene glycol, glycerol, amino or C 1-8 alkylamido;

Z is a bond or a group selected from CH 2 , (CH 2 ) 2 , CO, CH 2 CO, CH 2 CH 2 CO and CH 2 COCH 2 ;

Y is a bond;

R 6 is a mono- or poly(hydroxy or alkoxylated) alkyl group or a group of the formula OP(O) (OR 8 )R 7 ; and

R 7 is hydroxy, or an unsubstituted alkyl or aminoalkyl group.

10. The kit of claim 8 , wherein in the first compound of Formula I: R 3 is ethylene and each group R 1 represents —CH 2 COR 5 in which R 5 is hydroxy.

11. The kit of claim 8 , wherein the first compound is N,N′-dipyridoxyl ethylenediamine-N,N′-diacetic acid (PLED).

12. The kit of claim 8 , wherein the first compound is N,N′-bis-(pyridoxal-5-phosphate)-ethylenediamine-N,N′-diacetic acid (DPDP).

13. The kit of claim 12 , wherein the molar ratio of the MnPLED to DPDP is in the range of 1/100 to 99/100.

14. The kit of claim 8 , wherein the molar ratio of the MnPLED to the first compound is in the range of 1/100 to 99/100.

15. The pharmaceutical composition of claim 1 , comprising a cancer-inhibiting amount of the first compound.

16. The kit of claim 8 , wherein the preparation of the first active ingredient comprises a cancer-inhibiting amount of the first compound.