Synthesis and identification of novel indolo[2,3-a]pyrimido[5,4-c]carbazoles as a new class of anti-cancer agents

Pierce, Larry T.; Cahill, Michael G.; Winfield, Hannah; McCarthy, Florence O.

doi:10.1016/j.ejmech.2012.08.002

Cited by 26 publications

(10 citation statements)

References 19 publications

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“…Thus, we chose 7-azaindole and its halogeno derivatives, which fulfil the mentioned requirements [15]–[17]. Moreover, the biological perspective of 7-azaindole moiety, as recently proved on various 7-azaindole derivatives reported as having notable biological properties, such as anticancer activity [18], inhibition of kinases ( e.g . tropomyosin-related [19] or Abl and Src kinases [20]) or antiviral effect [21], has to be taken into account as well.…”

Section: Introductionmentioning

confidence: 99%

Pharmacological and Molecular Effects of Platinum(II) Complexes Involving 7-Azaindole Derivatives

et al. 2014

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The in vitro antitumour activity studies on a panel of human cancer cell lines (A549, HeLa, G-361, A2780, and A2780R) and the combined in vivo and ex vivo antitumour testing on the L1210 lymphocytic leukaemia model were performed on the cis-[PtCl2(naza)2] complexes (1–3) involving the 7-azaindole derivatives (naza). The platinum(II) complexes showed significantly higher in vitro cytotoxic effects on cell-based models, as compared with cisplatin, and showed the ability to avoid the acquired resistance of the A2780R cell line to cisplatin. The in vivo testing of the complexes (applied at the same dose as cisplatin) revealed their positive effect on the reduction of cancerous tissues volume, even if it is lower than that of cisplatin, however, they also showed less serious adverse effects on the healthy tissues and the health status of the treated mice. The results of ex vivo assays revealed that the complexes 1–3 were able to modulate the levels of active forms of caspases 3 and 8, and the transcription factor p53, and thus activate the intrinsic (mitochondrial) pathway of apoptosis. The pharmacological observations were supported by both the histological and immunohistochemical evaluation of isolated cancerous tissues. The applicability of the prepared complexes and their fate in biological systems, characterized by the hydrolytic stability and the thermodynamic aspects of the interactions with cysteine, reduced glutathione, and human serum albumin were studied by the mass spectrometry and isothermal titration calorimetric experiments.

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Section: Introductionmentioning

confidence: 99%

Pharmacological and Molecular Effects of Platinum(II) Complexes Involving 7-Azaindole Derivatives

et al. 2014

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“…This oxidation step was effected by photocyclization with iodine under continuous UV irradiation. 30 …”

Section: Chemical Synthesis Of Pqzsmentioning

confidence: 99%

“…29 Through replacement of the lactam ring in the prototypical kinase inhibitor staurosporine ( 57 ) with a bioisosteric pyrimidone ring, indolo[2,3- a ]pyrimido[5,4- c ]carbazole 58 was obtained as a novel anti-cancer agent to inhibit proliferation of various cancer cell lines in the low μM concentration range (Figure 5). 30 Finally, compound 2 is currently collected in the National Institutes of Health (NIH) molecular library and has been screened more 600 times in different assays, 66 and it was found to be active as an inhibitor of dual specificity tyrosine-phosphorylation-regulated kinase 1A (Dyrk1A), DNA repair proteins Rad52 and Rad54 (Table 1). These screening results still await further validation.…”

Section: Pharmacological Activities Of Pqzsmentioning

confidence: 99%

The chemistry and pharmacology of privileged pyrroloquinazolines

Chao

Xiao

2015

Med. Chem. Commun.

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The advent of next-generation sequencing (NGS) technology has plummeted the cost of whole genome sequencing, which has provided a long list of putative drug targets for a variety of diseases ranging from infectious diseases to cancers. The majority of these drug targets are still awaiting high-quality small molecule ligands to validate their therapeutic potential and track their druggability. Screening compound libraries based on privileged scaffolds is an efficient strategy to identify potential ligands to distinct biological targets. 7H-Pyrrolo[3,2-f]quinazoline (PQZ) is a potential privileged heterocyclic scaffold with diverse pharmacological properties. A number of biological targets have been identified for different derivatives of PQZ. This review summarized the synthetic strategies to access the chemical space associated with PQZ and discussed their unique biological profiles.

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“…These compounds have revealed the antiproliferative [1], anticancer [2][3][4][5] and anti-inflammatory [6] activities. They also act as protein kinase inhibitors in the treatment of kinase induced diseases [7,8]. 7-Azaindole has been used as a fluorescent tag alternative to tryptophan [9].…”

Section: Introductionmentioning

confidence: 99%

Reinvestigation of the crystal structure, vibrational spectroscopic studies and DFT calculations of 5-bromo-7-azaindole with dual N–H⋅⋅⋅N hydrogen bonds in dimers

Morzyk-Ociepa

Dysz

Turowska‐Tyrk

et al. 2015

Journal of Molecular Structure

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Synthesis and identification of novel indolo[2,3-a]pyrimido[5,4-c]carbazoles as a new class of anti-cancer agents

Cited by 26 publications

References 19 publications

Pharmacological and Molecular Effects of Platinum(II) Complexes Involving 7-Azaindole Derivatives

Pharmacological and Molecular Effects of Platinum(II) Complexes Involving 7-Azaindole Derivatives

The chemistry and pharmacology of privileged pyrroloquinazolines

Reinvestigation of the crystal structure, vibrational spectroscopic studies and DFT calculations of 5-bromo-7-azaindole with dual N–H⋅⋅⋅N hydrogen bonds in dimers

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