Compositions comprising fullerenyl mesochlorin nano-photosensitizers with covalently bound antibiotics and their uses in combination therapy

A fullerene/photosensitizer covalently-bonded antibiotic compound of the following formula (I):

• wherein
• Fn is a fullerene core, wherein Fn is C70;
• M is a metal ion selected from Mn, Ru, Rh, Pd, Pt, or Si;
• B is amino-C1-200 alkyl ether, amino-C1-200 alkyl, hydroxy-C1-200 alkyl ether, hydroxy-C1-200 alkyl, wherein the amino or hydroxyl is linked to a Ma carbonyl group as an amide or ester;
• Ma is —NH—CO-cyclopropanyl-CO— or —O—CO-cyclopropanyl-CO—;
• G is —CH(O—V2)—CH2— or —CH(O—CO—Z—V2)—CH2—;
• J is -E3-Abx;
• wherein Abx is an amino or amide group-containing antibiotic molecule;
• E1, E2, and E3 are each independently Y1,Y2-amino, (Y1,Y2-alkyl)-amino, Y1Y2-ethylenediamino, (dihydroxymethyl) alkylamino, (X1,X3-aryl)amino, X1,X3-aryloxy, Y2-alkoxy, Y1,Y2-alkoxy, (Y1,Y2-amino)alkoxy, (Y1,Y2,Y3-aryl)oxy, (dihydroxyalkyl)-aryloxy, (Y1,Y2,Y3-alkyl)amino, (Y1,Y2,Y3-aryl)amino, dihydroxyalkylamino, Y1,Y2,Y3-alkoxy, (trihydroxyalkyl)alkoxy, (trihydroxyalkyl)alkylamino, (dicarboxyalkyl)amino, Y2-thio, (Y1,Y2,Y3-alkyl)thio, (X1,X3-aryl)thio, (Y1,Y2-alkyl)thio, (dihydroxyalkyl)thio, Y1,Y2-dioxoalkyl, tri-(Y1,Y2,Y3-methylaminocarboxyethyl)methylamino, ((glycosidyl)oxoheteroaryl)amino, ((glycosidyl)oxoaryl)amino, (X1,X2,X3-heteroaryl)amino, (X1-diarylketone)amino, (T,X1-oxoaryl)amino, (T,X1-dioxoaryl)amino, (Y1-alkyl,Y2-alkyldioxoheteroaryl) amino, (Y1-alkyl,Y2-alkyldioxoaryl)amino, (di(Y1,Y2-methyl)dioxoheteroaryl)amino, (di(Y1,Y2-methyl)dioxoaryl)amino, ((glycosidyl)heteroaryl)amino, ((glycosidyl)aryl)amino, ((carboxylacetylalkyl)oxo-heteroaryl)amino, ((carboxylacetylalkyl)oxoaryl)amino, ((isopropylaminohydroxy-alkoxy)aryl)amino, (X1,X2,X3-alkylaryl)amino, (X1,X2,X3-heteroaryl)oxy, (isopropylaminohydroxyalkyl)aryloxy, (X1,X2,X3-oxoheteroaryl)oxy, (X1,X2,X3-oxoaryl)oxy, (X1,Y1-oxoheteroaryl)oxy, (X1-diarylketone)oxy, (T,X1-oxoaryl)oxy, (X1,X2-dioxoaryl)oxy, (Y1,Y2,di-aminodihydroxy)alkyl, (X1,X2-heteroaryl)thio, ((tricarboxylalkyl)ethylene-diamino)alkoxy, (X1,X2-oxoaryl)thio, (X1,X2-dioxoaryl)thio, (glycosidylheteroaryl)thio, (glycosidylaryl)thio, Y1-alkyl(thiocarbonyl)thio, Y1,Y2,-alkyl(thiocarbonyl)thio, Y1,Y2,Y3-alkyl(thiocarbonyl)thio, (Y1,Y2-aminothiocarbonyl)thio, (pyranosyl)thio, cysteinyl, tyrosinyl, (phenylalaninyl)amino, (dicarboxyalkyl)thio, (aminoaryl)1-100amino, (pyranosyl)1-100amino, (Y1-aminoaryl)1-100amino, (amino(sulfoaryl))1-100amino, peptidyl, thymidinyl, uridinyl, guanosinyl, adenosinyl, cholesteryl, or biotinylalkoxy;
• wherein T is halo;
• each of X1, X2, and X3 is each independently —Y2, —O—Y2, —S—Y2, —NH—Y2, —CO—O—Y2, —O—CO—Y2, —CO—NH—Y2, —CO—NY1Y2, —NH—CO—Y2, —SO2—Y2, —SO2—O—Y2, —CHY1Y2, or —NY1Y2;
• each of Y1, Y2, and Y3 is each independently —H, -Q-Z—H or —Z—H;
• in which each Q, independently, is —Ra—O—[Si(CH3)2—O—]1-100-, —C1-2000 alkyl-, —C6-40 aryl-, —C7-2000 alkylaryl-, —C7-2000 arylalkyl-, —(C1-30 alkyl ether)1-100-, —(C6-40 aryl ether)1-100-, —(C7-2000 alkylaryl ether)1-100-, —(C7-2000 arylalkyl ether)1-100-, —(C1-30 alkyl thioether)1-100-, —(C6-40 aryl thioether)1-100-, —(C7-2000 alkylaryl thioether)1-100-, —(C7-2000 arylalkyl thioether)1-100-, —(C2-50 alkyl ester)1-100-, —(C7-2000 aryl ester)1-100-, —(C8-2000 alkylaryl ester)1-100-, —(C8-2000 arylalkyl ester)1-100-, —Ra—CO—O—(C1-30 alkyl ether)1-100-, —Ra—CO—O—(C6-40 aryl ether)1-100-, —Ra—CO—O—(C7-2000 alkylaryl ether)1-100-, —Ra—CO—O—(C7-2000 arylalkyl ether)1-100-, —(C4-50 alkyl urethane)1-100-, —(C14-60 aryl urethane)1-100-, —(C10-2000 alkylaryl urethane)1-100-, —(C10-2000 arylalkyl urethane)1-100-, —(C5-50 alkyl urea)1-100-, —(C14-60 aryl urea)1-100-, —(C10-2000 alkylaryl urea)1-100-, —(C10-2000 arylalkyl urea)1-100-, —(C2-50 alkyl amide)1-100-, —(C7-60 aryl amide)1-100-, —(C8-2000 alkylaryl amide)1-100-, —(C8-2000 arylalkyl amide)1-100-, —(C3-30 alkyl anhydride)1-100-, —(C2-50 aryl anhydride)1-100-, —(C9-2000 alkylaryl anhydride)1-100-, —(C9-2000 arylalkyl anhydride)1-100-, —(C2-30 alkyl carbonate)1-100-, —(C7-50 aryl carbonate)1-100-, —(C8-2000 alkylaryl carbonate)1-100-, —(C8-2000 arylalkyl carbonate)1-100-, —Ra—O—CO—NH—(Rb or Ar—Rb—Ar)—NH—CO—O—(C1-30 alkyl ether, C6-40 aryl ether, C7-2000 alkylaryl ether, or C7-2000 arylalkyl ether)1-100-, —Ra—O—CO—NH—(Rb or Ar—Rb—Ar)—NH—CO—O—(C2-50 alkyl ester, C7-60 aryl ester, C8-2000 alkylaryl ester, or C8-2000 arylalkyl ester)1-100-, —Ra—O—CO—NH—(Rb or Ar—Rb—Ar)—NH—CO—O—(C1-30 alkyl ether, C6-40 aryl ether, C7-2000 alkylaryl ether, or C7-2000 arylalkyl ether)1-100-CO—NH—(Rb or Ar—Rb—Ar)—NH—CO—O—, —Ra—O—CO—NH—(Rb or Ar—Rb—Ar)—NH—CO—O—(C2-50 alkyl ester, C7-60 aryl ester, C8-2000 alkylaryl ester, or C8-2000 arylalkyl ester)1-100-Rc—O—CO—NH—(Rb or Ar—Rb—Ar)—NH—CO—O—, —Ra—NH—CO—NH—(Rb or Ar—Rb—Ar)—NH—CO—O—(C1-30 alkyl ether, C6-40 aryl ether, C7-2000 alkylaryl ether, or C7-2000 arylalkyl ether)1-100-, —Ra—NH—CO—NH—(Rb or Ar—Rb—Ar)—NH—CO—O—(C2-50 alkyl ester, C7-60 aryl ester, C8-2000 alkylaryl ester, or C8-2000 arylalkyl ester)1-100-, —Ra—NH—CO—NH—(Rb or Ar—Rb—Ar)—NH—CO—O—(C1-30 alkyl ether, C6-40 aryl ether, C7-2000 alkylaryl ether, or C7-2000 arylalkyl ether)1-100-CO—NH—(Rb or Ar—Rb—Ar)—NH—CO—O—, —Ra—NH—CO—NH—(Rb or Ar—Rb—Ar)—NH—CO—O—(C2-50 alkyl ester, C7-60 aryl ester, C8-2000 alkylaryl ester, or C8-2000 arylalkyl ester)1-100-Rc—O—CO—NH—(Rb or Ar—Rb—Ar)—NH—CO—O—, —Ra—O—CO—NH—(Rb or Ar—Rb—Ar)—NH—CO—NH—(C2-50 alkyl amide, C7-60 aryl amide, C8-2000 alkylaryl amide, or C8-2000 arylalkyl amide)1-100-, —Ra—NH—CO—NH—(Rb or Ar—Rb—Ar)—NH—CO—NH—(C2-50 alkyl amide, C7-60 aryl amide, C8-2000 alkylaryl amide, or C8-2000 arylalkyl amide)1-100-, —CH2—CH(OH)—CH2—(OCH2CH2)1-100—, OCH2CH(OH)—CH2—, —CH2—CH(OH)—CH2—N+HRa—(CH2CH2N+RaRb)1-100—CH2CH2N+HRa—CH2CH(OH)CH2—, or —CH2CH2—N+RaRb—(CH2CH2N+RaRb)1-100—Rc—;
• and
• each Z, independently, is —Ra—, —Ra—Ar—, —Ar—Ra—, or —Ar—;
• and
• V1 and V2 independently are hydrogen, C1-2000 alkyl, C6-40 aryl, or C7-2000 alkyl aryl, optionally substituted with —OH, —SH, —NH2, —NHOH, —SO3H, —OSO3H, —CO2H, —CONH2, —CONHNH2, —CH(NH2)—CO2H, —NH—CH2—CO2H, —P(OH)3, —PO(OH)2, —O—PO(OH)2, —O—PO(OH)—O—PO(OH)2, —O—PO(O—)—O—CH2CH2NH3+, —O—PO(O)—O—CH2CH2—N+(CH3)3, -glycoside, -oligosaccharide, —CO-glycoside, —CO-oligosaccharide, —OCH3, —OCH2(CHOH)4—CH2OH, —OCH2(CHOH)2—CH2OH, —CO—OCH2(CHOH)4—CH2OH, —C6H3(OH)2, —N(CH2CO2H)2, —CO—N(CH2CO2H)2, —CO—NH—C(CH2CH2CO2H)3, —CO—NH—C(CH2CH2OH)3, —[CH2—CH(CO2Ra)]1-100—H, —O—(CH2CH2O)1-100—H, —NH3+, —N+H2Ra, —N+HRaRb, or —N+RaRbRc;
• wherein each of Ra, Rb, and R0 are each independently C1-20 linear or branched alkyl;
• Ar is aryl;
• W is hydroxyl or amino;
• p and s each independently is 0-20;
• q is 1;
• and
• r is 0 or 1 provided that at least one occurrence of r is 1.