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- DNA and the chromosome – varied targets for chemotherapy

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Figure 1 Levels of Drug/DNA Interactions: A) The first level of interaction is the direct drug interaction with the DNA. Drug binding frequency and sequence preferences are two examples of evaluations of this level. B) The second level involves the disruption of DNA interactions with other molecules that result from the drug/DNA interaction such as DNA/protein interactions. Another possibility (not shown) is the alteration or stabilization of DNA secondary structures. C) The third level is the changes in nuclear activities such as transcription, replication, and repair or disruption in complex ternary structures. Green circles, drug/DNA adduct; black lines, DNA strands, chromosome (with loops); yellow oval, red oval, and pink circle, DNA associated proteins; blue square, protein modification such as phosphorylation or methylation.

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Figure 2 Chemical Structures 1–8. The chemical structures of chlorambucil, melphalan, cyclophosphamide, streptozotocin, dacarbazine, temozolomide, mitomycin C, FR 900482. Compounds are referred to in text by number in [#].

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Figure 3 Chemical Structures 9–13. The chemical structures of CC-1065, adozelesin, bizelesin, and the aminoindoline compounds [12] and [13].

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Figure 4 Chemical Structures 14–18. The chemical structures of tallimustine, distamycin A, [16], Et-743, and phthalascidin.

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Figure 5 DNA Secondary Structures: G-Tetrad and G-quadruplex. A) Schematic illustration of G-tetrad, four guanine bases in a planar arrangement through Hoogsteen hydrogen bonds; B) G-quadruplex, parallel arrangement of four DNA strands; C) Intermolecular G-quadruplex, DNA sequences with G-rich repeats forming hairpins that dimerize to stablize bimolecular structure; and D) anti-parrallel intramolecular G-quadruplex (fold-over G-quadruplex), single DNA strand with four G-rich repeats that can fold upon themselves to form the quadruplex structure (adapted from Han and Hurley [32]).

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Figure 6 Chemical Structures 19–22. The chemical structures of BSU-1051, [20], TMPyP4, and PIPER.

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Figure 7 Chemical Structures 23–31. The chemical structures of actinomycin D, [24-27], bisacridine, BePI, 9-OH-B220, and neomycin.

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Figure 8 Chemical Structures 32–35. The chemical structures of camptothecin, doxorubicin, etoposide, and fostriecin.

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Figure 9 Chemical Structures 36–40. The chemical structures of 5-azacytidine, decitabine, SAHA, FR 901228, and cisplatin.

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