Development of 4,4'-dibromobinaphthalene analogues with potent photo-inducible DNA cross-linking capability and cytotoxicity towards breast MDA-MB 468 cancer cells

Photoinduced DNA cross-linking process showed advantages of high spatio-temporal resolution and control. We have designed, synthesized, and characterized several 4,4 & PRIME;-dibromo binaphthalene analogues (1a-f) that can be activated by 350 nm irradiation to induce various DNA damage, including DNA interstrand cross-links (ICL) formation, strand cleavages, and alkaline labile DNA lesions. The degree and types of DNA damage induced by these compounds depend on the leaving groups of the substrates, pH value of the buffer solution, and DNA sequences. The DNA ICL products were produced from the carbocations formed via the oxidation of free radicals photo-generated from 1a-f. Most of these compounds alone exhibited minimum cytotoxicity towards cancer cells while 350 nm irradiation greatly improved their anticancer effects (up to 40-fold enhancement) because of photo-induced cellular DNA damage. This work provides guidance for further design of photo-inducible DNA cross-linking agents as potent photo-activated anticancer prodrugs with good control over toxicity and selectivity.