cc-1065 and cyclopropane

cc-1065 has been researched along with cyclopropane* in 2 studies

Other Studies

2 other study(ies) available for cc-1065 and cyclopropane

Article	Year
DNA interstrand crosslinking agents: synthesis, DNA interactions, and cytotoxicity of dimeric achiral seco-amino-CBI and conjugates of achiral seco-amino-CBI with pyrrolobenzodiazepine (PBD). Bioorganic & medicinal chemistry letters, 2006, Nov-01, Volume: 16, Issue:21 The design and synthesis of three novel bisalkylating agents derived from the achiral seco-duocarmycin or CC-1065 analogs and pyrrolobenzodiazepines (PBDs) are described: achiral seco-CBI (cyclopropanebenz[e]indoline)-PBD 11, achiral seco-CI-PBD 12, and achiral seco-CBI dimer 13. Compounds 11 and 12 demonstrated enhanced cytotoxicity over the monomer counterparts against the growth of P815 murine mastocytoma cells in culture. Conjugate 11 was found to covalently react with adenine-N3 positions within the minor groove at AT-rich sequences and to produce DNA interstrand crosslinks. Both compounds were found to induce apoptosis in P815 cells. Due to its poor water solubility, dimer 13 did not give any appreciable DNA binding or cytotoxicity. Topics: Benzodiazepines; Cross-Linking Reagents; Cyclopropanes; Dimerization; DNA; Indoles; Pyrroles	2006
Nucleophilic cyclopropane ring opening in duocarmycin SA derivatives by methanol under acid conditions: a quantum mechanical study in the gas-phase and in solution. The Journal of organic chemistry, 2004, Apr-16, Volume: 69, Issue:8 We present a quantum-mechanical study of the S(N)2 acid-catalyzed solvolysis with methanol of seven simplified duocarmycin SA (DNA alkylating agent) derivatives characterized by spirocyclic systems of increasing complexity, all containing the cyclopropyl/cyclohexadienone substrate. The reaction has been studied at the DFT-PBE0/6-31G(d) level in the gas phase and in methanol solution, using in the latter case the polarizable continuum model (PCM) to describe solvent effects. The results delivered by this computational protocol are in full agreement with the available experimental evidences and are not modified by extension of the basis set or by using a second-order many-body treatment (MP2) in place of DFT. This allows investigation of substituent effects in terms of structure/reactivity relationships and evaluation of the role of stereoelectronic effects. Furthermore, reactivity indices (hardness, electrophilicity) have been computed and shown to correlate well with activation energies. Together with their intrinsic interest, the details of the mechanism of the acid-catalyzed nucleophilic addition to the activated cyclopropane issuing from the present study pave the route for a deeper understanding of the molecular basis for the remarkable profile of the DNA-alkylation by DSA derivatives. Topics: Antibiotics, Antineoplastic; Catalysis; Cyclopropanes; Duocarmycins; Gases; Hydrogen-Ion Concentration; Indoles; Methanol; Molecular Structure; Pyrroles; Solutions	2004

Article

Year

DNA interstrand crosslinking agents: synthesis, DNA interactions, and cytotoxicity of dimeric achiral seco-amino-CBI and conjugates of achiral seco-amino-CBI with pyrrolobenzodiazepine (PBD).

Bioorganic & medicinal chemistry letters, 2006, Nov-01, Volume: 16, Issue:21

The design and synthesis of three novel bisalkylating agents derived from the achiral seco-duocarmycin or CC-1065 analogs and pyrrolobenzodiazepines (PBDs) are described: achiral seco-CBI (cyclopropanebenz[e]indoline)-PBD 11, achiral seco-CI-PBD 12, and achiral seco-CBI dimer 13. Compounds 11 and 12 demonstrated enhanced cytotoxicity over the monomer counterparts against the growth of P815 murine mastocytoma cells in culture. Conjugate 11 was found to covalently react with adenine-N3 positions within the minor groove at AT-rich sequences and to produce DNA interstrand crosslinks. Both compounds were found to induce apoptosis in P815 cells. Due to its poor water solubility, dimer 13 did not give any appreciable DNA binding or cytotoxicity.

Topics: Benzodiazepines; Cross-Linking Reagents; Cyclopropanes; Dimerization; DNA; Indoles; Pyrroles

2006

Nucleophilic cyclopropane ring opening in duocarmycin SA derivatives by methanol under acid conditions: a quantum mechanical study in the gas-phase and in solution.

The Journal of organic chemistry, 2004, Apr-16, Volume: 69, Issue:8

We present a quantum-mechanical study of the S(N)2 acid-catalyzed solvolysis with methanol of seven simplified duocarmycin SA (DNA alkylating agent) derivatives characterized by spirocyclic systems of increasing complexity, all containing the cyclopropyl/cyclohexadienone substrate. The reaction has been studied at the DFT-PBE0/6-31G(d) level in the gas phase and in methanol solution, using in the latter case the polarizable continuum model (PCM) to describe solvent effects. The results delivered by this computational protocol are in full agreement with the available experimental evidences and are not modified by extension of the basis set or by using a second-order many-body treatment (MP2) in place of DFT. This allows investigation of substituent effects in terms of structure/reactivity relationships and evaluation of the role of stereoelectronic effects. Furthermore, reactivity indices (hardness, electrophilicity) have been computed and shown to correlate well with activation energies. Together with their intrinsic interest, the details of the mechanism of the acid-catalyzed nucleophilic addition to the activated cyclopropane issuing from the present study pave the route for a deeper understanding of the molecular basis for the remarkable profile of the DNA-alkylation by DSA derivatives.

Topics: Antibiotics, Antineoplastic; Catalysis; Cyclopropanes; Duocarmycins; Gases; Hydrogen-Ion Concentration; Indoles; Methanol; Molecular Structure; Pyrroles; Solutions

2004