Promising carboranylquinazolines for boron neutron capture therapy: synthesis, characterization, and in vitro toxicity evaluation.
Novel classes of structurally different boronated quinazolines were designed bearing 22-37% boron by weight for potential application in BNCT of tumors. Firstly, the o-carborane cage was linked to quinazoline at C-2 position via thioether linker: 2-S-(1,2-dicarba-closo-dodecaboran(12)-1-ylmethyl)-3-phenylquinazolin-4(3H)-one. Secondly, the o-carborane cage connected to quinazoline moiety at C-4 position through an ether linkage: 4-O-(o-carboran-1-ylmethyl)-2-methylquinazoline. Finally, carborane moieties were also linked to the C-6 position of quinazoline: 6-[N-{3-(2-methyl-1,2-dicarba-closo-dodecaboran(12)-1-yl)methyl}benzylidinamino]quinazolin-4(3H)-one and 6-[N-{3,5-di(2-methyl-1,2-dicarba-closo-dodecaboran(12)-1-yl)methyl}benzylidinamino]quinazolin-4(3H)-one. The water solubility was achieved by the degradative conversion of the o-carboranylquinazolines to the corresponding potassium nido-carboranyl quinazolines: 2-S-(1,2-dicarba-nido-undecacarborate-1-ylmethyl)-3-phenylquinazolin-4(3H)-one, 4-O-(1,2-dicarba-nido-undecacarborate-1-ylmethyl)-2-methylquinazoline, 6-[N-{3-(2-methyl-1,2-dicarba-nido-undecacarborate-1-yl)methyl}benzylidinamino]quinazolin-4(3H)-one and 6-[N-{3,5-di(2-methyl-1,2-dicarba-nido-undecacarborate-1-yl)methyl}benzylidinamino]quinazolin-4(3H)-one. The products were confirmed by NMR, elemental analysis, IR, and mass spectrometry. In vitro toxicity was performed with B16 melanoma cells and showed that the connection of hydrophilic nido-carborane to quinazoline moiety decreases the compound's toxicity. This cytotoxicity effect was not observed in the nido-carborane containing two cluster units which was relatively nontoxic and did not inhibit colony formation up to concentrations of 300microg boron ml(-1). The compounds described here can be considered as new candidates for BNCT.
Genady
Afaf R
AR
Department of Chemistry, Faculty of Science, University of Tanta, 31527 Tanta, Egypt. afafgenady@hotmail.com
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001880:Boranes / Q000138:chemical synthesis* / Q000494:pharmacology; D016754:Boron Neutron Capture Therapy; D045744:Cell Line, Tumor; D006801:Humans; D008546:Melanoma, Experimental / Q000188:drug therapy; D011799:Quinazolines / Q000138:chemical synthesis* / Q000494:pharmacology; D013057:Spectrum Analysis; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D001880:Boranes; D011799:Quinazolines