Topotecan - CAS 123948-87-8

Topotecan - CAS 123948-87-8 Catalog number: BADC-00328

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Topotecan has been used as a positive control for the identification and analysis of HIF-1α and VEGF inhibitors in human glioma cells under hypoxic conditions. It has also been used for in vitro apoptosis assays in PA317 cells.

General Information

Category
ADCs Cytotoxin
Product Name
Topotecan
CAS
123948-87-8
Catalog Number
BADC-00328
Molecular Formula
C23H23N3O5
Molecular Weight
421.45

Chemical Structure

  • Topotecan
Purity
≥95%
Appearance
Soild powder
Synonyms
(S)-10-((dimethylamino)methyl)-4-ethyl-4,9-dihydroxy-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione hydrochloride;Hycamtin; SKF104864; SKF 104864; SKF-104864
Melting Point
>155 °C (dec.)
Canonical SMILES
CC[C@@]1(c2cc3n(c(=O)c2COC1=O)Cc4c3nc5ccc(c(c5c4)CN(C)C)O)O
InChI Key
UCFGDBYHRUNTLO-QHCPKHFHSA-N
InChI
InChI=1S/C23H23N3O5/c1-4-23(30)16-8-18-20-12(9-26(18)21(28)15(16)11-31-22(23)29)7-13-14(10-25(2)3)19(27)6-5-17(13)24-20/h5-8,27,30H,4,9-11H2,1-3H3/t23-/m0/s1
1. Mode of binding of camptothecins to double helix oligonucleotides
Stefania Mazzini, Maria Cristina Bellucci, Sabrina Dallavalle, Franca Fraternali and Rosanna Mondelli *. Org. Biomol. Chem. , 2004, 2, 505–513
Actually, the mode of binding of Cpts to DNA in absence of the enzyme is still unclear and the published results on the DNA/Cpt interactions are confusing and contradictory. Cpt was first described as a prototypical Topo-I poison that exhibits little or no binding to either DNA or Topo-I alone. More recently two clinically important Cpt derivatives, topotecan (Tpt) 1 and irinotecan, were shown to be capable of binding with DNA in the absence of Topo-I, but no data on the molecular structure of Cpt/DNA complexes have been published. The results from linear dichroism spectroscopy appear difficult to interpret; binding in the major groove was suggested by some authors, others claimed to have recognized two types of complexes with calf-thymus DNA, and concluded for a binding in the minor groove. Two NMR studies on Tpt/DNA binding have been reported, but the results, based only on chemical shift values, are contradictory. Yao et al. claimed a sequence specificity for duplex DNA containing dT, whereas Yang et al. reported a specific intercalation of topotecan into dGdC rather than dAdT sequences. An intercalation type of binding has also been suggested by Pilch et al.
2. Integrated computational strategies for UV/vis spectra of large molecules in solution
Vincenzo Barone* and Antonino Polimeno. Chem. Soc. Rev., 2007, 36, 1724–1731
Let us consider, for purposes of illustration, an example in which even a semi-quantitative approach (i.e. vertical excitations with a basic non-equilibrium solvent model) provides results of remarkable interest for the individuation of spectroscopic signatures in large molecules of biological interest. Topotecan is the most commonly used agent for the treatment of ovarian carcinoma, and is the only single agent currently approved in the United States for the treatment of small-cell lung cancer recurrent disease, which is among the most lethal malignancies. Since the drug displays a high degree of toxicity also against normal tissues that show enhanced proliferative rates, a deeper understanding of structure–property relationships is of considerable interest. At concentrations low enough to avoid dimer formation, tautomeric forms with charge +1 (see Fig. 3) dominate in the pH range 4–6.
3. Live-cell monitoring of the glutathione-triggered release of the anticancer drug topotecan on gold nanoparticles in serum-containing media
Mira Kim, Kwangsu Ock, Keunchang Cho, Sang-Woo Joo* and So Yeong Lee*. Chem. Commun., 2012, 48, 4205–4207
Topotecan (TOPO) is a camptothecin compound, one of the topoisomerase I inhibitors resulting in the accumulation of single-stranded breaks in DNA. Topotecan (TOPO) has its own fluorescence emission maximum at 530 nm, quite close to the absorption bands of AuNPs. The camptothecin compounds may adsorb onto Au surfaces. Fluorescence appears to be quenched on Au surfaces via nanometal surface energy transfer (NSET), which may be utilized in biomolecular imaging.
4. Cyclometalated gold(III) complexes with N-heterocyclic carbene ligands as topoisomerase Ⅰ poisons
Jessie Jing Yan, Andy Lok-Fung Chow, Chung-Hang Leung, Raymond Wai-Yin Sun, Dik-Lung Ma and Chi-Ming Che*. Chem. Commun., 2010, 46, 3893–3895
To gain insight into the structural basis of the TopoI-linked DNA complex stabilization by 1, we used flexible-ligand docking module of ICM-Pro 3.6–1 molecular software (Molsoft). Analysis of the low energy metal complex conformations revealed that 1 binds to TopoI-linked DNA in a manner similar to the binding by topotecan, a derivative of CPT (Fig. 4), with a calculated binding energy of -9.7 kcal/mol (cf., calculated binding of topotecan = -11.6 kcal/mol). The proposed binding mode of 1 partially overlaps with that of topotecan and there is no hydrogen bond between TopoI and 1, in contrast to the presence of a direct hydrogen bonds between Asp533 and topotecan, and between Arg364 and topotecan, in the TopoI-DNA-topotecan complex.

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