DNA bifunctional intercalators: Antileukemic activity of new pyridocarbazole dimers

Comparison of the bis‐intercalating complexes formed between either ditercalinium or a flexible analogue and d(CpGpCpG)2 or d(TpTpCpGpCpGpApA)2 minihelices: 1H‐ and 31P‐nmr analyses

“…In the case of octanucleotide complexes, this B-DNA sequential pattern is interrupted a t the two intercalation sites. The NOE between H8 of guanine 4 (respectively guanine 6 at the second site) and HI, or H2" of cytosine 3 (respectively cytosine 5 a t the second site) disappears. This cannot be seen clearly in the analogue-tetranucleotide complex, because the NOESY contains exchange cross peaks between the free and bound forms a t the 2 : 1 helix to drug ratio, preventing differentiation between exchange relaxation and NOE relaxation.…”

“…NOEs are pointed out. In the octanucleotide complexes, as in the tetranucleotide ones, the D8 (and D9) protons give NOEs with the H18 and HPM of cytosine 5 (as does H8 of guanine 6 in the free octanucleotide), and a weak effect (seen in the octanucleotide-analogue complex) with H8 of guanine 6 (as do Hlr and H2" of cytosine 5 in free octanucleotide) .…”

Tight Binding of the Antitumor Drug Ditercalinium to Quadruplex DNA

“…[1,2] This 7H-pyridocarbazole dimer binds from the major groove side of the double helix to form bis-intercalation complexes with the two pyridocarbazolium rings inserted between contiguous CpG steps. [3,4] The bis intercalation places the positively charged, rigid bis(ethylpiperidinium) linker chain within the major groove of the helix and induces a significant bend in the helix axis of about 158 towards the minor groove.…”

Synthesis and Cytotoxic Activity of Dimeric Analogs of Acronycine in the Benzo[b]pyrano[3,2-h]acridin-7-one Series

“…Ditercalinium (1), resulting from the dimerization of two pyridocarbazole units related to natural alkaloids ellipticine (2) and olivacine (3) is an excellent example of this approach. [7][8][9] Benzo [b]acronycine derived antitumor derivatives, developed from the model of natural acronycine (4), [10][11][12][13][14] are exemplified by diacetate 5, currently under phase I clinical trials under the code S23906-1. 15,16) These compounds displayed a particularly impressive broad antitumor spectrum, when evaluated against aggressive orthotopic models of human ovarian, lung, and colon cancers.…”