ChemInform Abstract: Synthesis and Analysis of Structural Features of Phenoxazine Analogues Needed to Reverse Vinblastine Resistance in Multidrug Resistant (MDR) Cancer Cells.

Eregowda, G. B.; Kalpana, H. N.; Hegde, Rajesh N.; Thimmaiah, Κ. N.

doi:10.1002/chin.200102157

Cited by 5 publications

(6 citation statements)

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“…Phenothiazines 1a and 1b , phenoxazines 3a – 3d , 1-phenylpiperazines, 5 H -dibenzo[ b , f ]azepine 9 , 10,11-dihydro-5 H -dibenz[ b , f ]azepine 10 , acridone 11 (Scheme ), diphenylamine 12 , 2-phenoxyaniline 13 , anilines, and benzylamine precursors for 22a – 22b were purchased or synthesized according to literature methods. The starting 2-chloro-10 H -phenoxazine 3b and 2,8-dichloro-10 H -phenoxazine 3c were prepared in five steps starting via a 2-amino-2′-chlorodiaryl ether according to literature procedures . The 10 H -phenoxazine-3-carbonitrile 3d was prepared as described by Eastmond et al In general, synthesis of various intermediate carbamoyl chlorides 14 was accomplished without isolating them by chlorocarbonylation of N -heterocycles or secondary amines with bis(trichloromethyl) carbonate in 1,2-dichloroethane and pyridine, as illustrated in Scheme .…”

Section: Chemistrymentioning

confidence: 99%

N-Heterocyclic (4-Phenylpiperazin-1-yl)methanones Derived from Phenoxazine and Phenothiazine as Highly Potent Inhibitors of Tubulin Polymerization

et al. 2017

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We report here a series of 27 10-(4-phenylpiperazin-1-yl)methanones derived from tricyclic heterocycles which were screened for effects on tumor cell growth, inhibition of tubulin polymerization, and induction of cell cycle arrest. Several analogues, among them the 10-(4-(3-methoxyphenyl)piperazine-1-carbonyl)-10H-phenoxazine-3-carbonitrile (16o), showed excellent antiproliferative properties, with low nanomolar GI values (16o, mean GI of 3.3 nM) against a large number (93) of cancer cell lines. Fifteen compounds potently inhibited tubulin polymerization. Analysis of cell cycle by flow cytometry revealed that inhibition of tumor cell growth was related to an induction of G2/M phase cell cycle blockade. Western blotting and molecular docking studies suggested that these compounds bind efficiently to β-tubulin at the colchicine binding site. Our studies demonstrate the suitability of the phenoxazine and phenothiazine core and also of the phenylpiperazine moiety for the development of novel and potent tubulin polymerization inhibitors.

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Section: Chemistrymentioning

confidence: 99%

N-Heterocyclic (4-Phenylpiperazin-1-yl)methanones Derived from Phenoxazine and Phenothiazine as Highly Potent Inhibitors of Tubulin Polymerization

et al. 2017

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“…Earlier studies on the secondary metabolites produced by C. gambosa, demonstrated that in culture, this fungal species synthesized an orange crystalline metabolite which was shown to be the phenoxazine derivatives (phenoxazone and a-amino-phenoxazone) (Clemencon, 1987;Moncalvo et al, 1991;Schlunegger et al, 1976). These derivatives are used extensively in medicine, biology and chemistry (Eregowda et al, 2000;Kalpana et al, 1999;Shimizu et al, 2004;Sridhar et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

In vitro antifungal activity of Calocybe gambosa extracts against yeasts and filamentous fungi

Angelini¹,

Tirillini²,

Venanzoni³

2012

Afr. J. Microbiol. Res.

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Three strains of Calocybe gambosa (Fr.) Donk were investigated as possible sources of biologically active substances with antifungal activity. After submerged cultivation of C. gambosa mycelium, biologically active materials were isolated as ethyl acetate extracts from culture liquids. The in vitro activity of these C. gambosa extracts (Cg1, Cg2, Cg3) against yeasts and filamentous fungi was evaluated using the Clinical and Laboratory Standards Institute (CLSI) M27-A2 and M38-A2. The minimum inhibitory concentration (MIC) against most of the tested clinical fungal strains for Cg1 and Cg2 extracts ranges from 12.5 to 50 µg/ml while Cg3 ranged from 1.56 to 12.5 µg/ml. Candida albicans (DBVPG 4268) were the most sensitive fungal strain to C. gambosa extracts, with MIC ranges of 1.56 to 12.5 µg/mL, while the strains of Aspergillus tubingensis showed the least sensitivity to the extracts. The high performance liquid chromatography (HPLC) fingerprint of the isolates shows four principal compounds produced by the cultured mycelium. Considering the potential use of natural antifungal compounds in medicine, we are currently working on a small-scale extraction, isolation and structural characterization of compounds produced from the C. gambosa.

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“…Actinomycin D ( 13 ), bearing a phenoxazine chromophore, represents one of the older chemotherapy drugs and is primarily used as an investigative tool in cell biology to inhibit transcription . Meanwhile, the anticancer activities of several phenoxazinones on human leukemia cell lines have also been investigated. − In addition, N -substituted phenoxazines have recently been identified as modulators of MDR , and as potent specific inhibitors of Akt signaling …”

Section: Introductionmentioning

confidence: 99%

N-Benzoylated Phenoxazines and Phenothiazines: Synthesis, Antiproliferative Activity, and Inhibition of Tubulin Polymerization

et al. 2011

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A total of 53 N-benzoylated phenoxazines and phenothiazines, including their S-oxidized analogues, were synthesized and evaluated for antiproliferative activity, interaction with tubulin, and cell cycle effects. Potent inhibitors of multiple cancer cell lines emerged with the 10-(4-methoxybenzoyl)-10H-phenoxazine-3-carbonitrile (33b, IC(50) values in the range of 2-15 nM) and the isovanillic analogue 33c. Seventeen compounds strongly inhibited tubulin polymerization with activities higher than or comparable to those of the reference compounds such as colchicine. Concentration-dependent flow cytometric studies revealed that inhibition of K562 cell growth was associated with an arrest in the G2/M phases of the cell cycle, indicative of mitotic blockade. Structure-activity relationship studies showed that best potencies were obtained with agents bearing a methoxy group placed para at the terminal phenyl ring and a 3-cyano group in the phenoxazine. A series of analogues highlight not only the phenoxazine but also the phenothiazine structural scaffold as valuable pharmacophores for potent tubulin polymerization inhibitors, worthy of further investigation.

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ChemInform Abstract: Synthesis and Analysis of Structural Features of Phenoxazine Analogues Needed to Reverse Vinblastine Resistance in Multidrug Resistant (MDR) Cancer Cells.

Cited by 5 publications

References 0 publications

N-Heterocyclic (4-Phenylpiperazin-1-yl)methanones Derived from Phenoxazine and Phenothiazine as Highly Potent Inhibitors of Tubulin Polymerization

N-Heterocyclic (4-Phenylpiperazin-1-yl)methanones Derived from Phenoxazine and Phenothiazine as Highly Potent Inhibitors of Tubulin Polymerization

In vitro antifungal activity of Calocybe gambosa extracts against yeasts and filamentous fungi

N-Benzoylated Phenoxazines and Phenothiazines: Synthesis, Antiproliferative Activity, and Inhibition of Tubulin Polymerization

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