Antitumor Agents. 2. Synthesis, Structure−Activity Relationships, and Biological Evaluation of Substituted 5<i>H</i>-Pyridophenoxazin-5-ones with Potent Antiproliferative Activity

Bolognese, Adele; Correale, Gaetano; Manfra, Michele; Lavecchia, Antonio; Mazzoni, Orazio; Novellino, Ettore; Barone, Vincenzo; Colla, Paolo La; Loddo, Roberta

doi:10.1021/jm020918w

Cited by 56 publications

(60 citation statements)

References 12 publications

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“…The specific role of the bioactivity of pyridine ring has been recognized and the introduction of some pyridine analogs into the molecules of drugs could result in new compounds that have significant biological activity compared with the parent compounds Straub et al, 1997;Bolognese et al, 2002;Tiwari et al, 2002;Kuo et al, 2005). It was also reported that a diverse array of naturally occurring alkaloids in sponges exhibit potent bioactivities because of the presence of a pyridine moiety (Vincent et al, 1997;Gordon et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Design, synthesis, and biological evaluation of novel pyridine acid esters of podophyllotoxin and esters of 4′-demethylepipodophyllotoxin

Liu

Tian

2007

Med Chem Res

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Podophyllotoxin and related analogs present numerous challenges associated with optimal antitumor activity and severe unpredictable toxicity. In the course of our ongoing investigation of quantitative structure-activity relationships to find biorational antitumor drugs, two series of pyridine acid ester derivatives of podophyllotoxin and 4 0 -demethylepipodophyllotoxin have been prepared by reacting the corresponding pyridine acids with the hydroxyl group of podophyllotoxin and 4 0 -demethyl epipodophyllotoxin in the presence of dimethylaminopyridine (DMAP) and N,N-dicyclohexylcarbodiimde (DCC). The structures of the compounds were extensively characterized by using 1 H-nuclear magnetic resonance, mass spectroscopy, infrared, and elemental analysis and evaluated for their in vitro cytotoxicity on two neoplastic cell lines (P-388 murine leukemia, A-549 human lung carcinoma) using a MTT-based assay, the results indicated significantly higher efficacy of these compounds in comparison with the prototypical inhibitor etoposide. On the basis of the preliminary biological testing results, it suggested that the cytotoxic activity of OCH 3 at C-4 0 is more potent than that of its demethylated analogs and the podophyllotoxin substitution at C-4 may be optimal for synthesizing more potent cytotoxic compounds.

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Section: Introductionmentioning

confidence: 99%

Design, synthesis, and biological evaluation of novel pyridine acid esters of podophyllotoxin and esters of 4′-demethylepipodophyllotoxin

Liu

Tian

2007

Med Chem Res

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“…Moreover, the dimethyl derivatives 1 and 2 displayed an enhanced specificity toward some tumor cell lines compared with the corresponding monomethylated analogues previously described. 10 Compound 2 revealed a distinct specificity toward two lymphoma/leukemia cells, CD4 + acute T-lymphoblastic leukemia (C8166) and acute B-lymphoblastic leukemia (CCRF-SB) as well as two carcinoma cells, colon adenocarcinoma (HT-29) and nasopharyngeal carcinoma (KB). Compound 5 exhibited specificity against 5637 carcinoma cells and MT-4 leukemia cells.…”

Section: Resultsmentioning

confidence: 99%

Antitumor Agents. 5. Synthesis, Structure−Activity Relationships, and Biological Evaluation of Dimethyl-5H-pyridophenoxazin-5-ones, Tetrahydro-5H-benzopyridophenoxazin-5-ones, and 5H-Benzopyridophenoxazin-5-ones with Potent Antiproliferative Activity

et al. 2006

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New antiproliferative compounds, dimethyl-5H-pyrido[3,2-a]phenoxazin-5-ones (1-6), tetrahydro-5H-benzopyrido[2,3-j]phenoxazin-5-ones (7-9), and 5H-benzopyrido[3,2-a]phenoxazin-5-ones (10-12) were synthesized and evaluated against representative human neoplastic cell lines. Dimethyl derivatives 1-6 were more active against carcinoma than leukemia cell lines. The tetrahydrobenzo derivatives 7-9 were scarcely active, whereas the corresponding benzo derivatives 10-12 showed notable cytotoxicity against a majority of the tested cell lines. Molecular modeling studies indicated that the high potency of 10 and 11, the most cytotoxic compounds of the whole series, could be due to the position of the condensed benzene ring, which favors pi-pi stacking interactions with purine and pyrimidine bases in the DNA active site. Biological studies suggested that 10-12 have no effect on human topoisomerases I and II and that they induce arrest at the G2/M phase.

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“…They possess various biological activities such as antimicrobial [3], hypolipidacmic [4], antidiabetic [5], anti-inflammatory [6], antimycobacterial [7], antithrombotic [8], antagonism to progesterone receptor [9], antitumor [10], antiviral [11], leucocyte clastase [12] and scrotonin reuptakes [13]. The ground state equilibration of organic compounds was established using spectroscopic data [14].…”

Section: Intrductionmentioning

confidence: 99%

Hammett Spectral Correlations in some Aryl 1,3-Oxazine-4-Thione Derivatives

Thirunarayanan

Sekar

2014

ILCPA

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A series of some aryl 1,3-oxazine-4-thione derivatives have been synthesized by 1-methyl imidazole catalyzed three component one pot synthetic method in room temperature. The purities of these thiones were studied by their physical constants and spectroscopic data. The infrared and 13 C NMR spectral data of CN and CS were correlated with Hammett substituent constants, F and R parameters using single and multi-linear regression analysis. From the results of statistical analysis, the effect of substituent on the spectral data was studied.Keywords: 1,3-oxazine-4-thiones; IR spectra; 13 C NMR spectra; Hammett correlation INTRDUCTIONAryl 1,3-oxazine-4-thiones are pharmaceutical important heterocycles [1,2] [21]. The spatial arrangement of protons such as cis and trans of organic stereo chemical compounds [22] were studied using NMR spectra. Currently chemists and spectroscopic researchers [23][24][25][26][27][28][29] have paid much more interest for correlation of spectral data with Hammett substituent constants. Thirunarayanan and Ravi [30] have studied the effect of substituents of some pyrazoline-1-ethanones. Substituent effects on the spectral group frequencies of 9H-fluorenayl bromides were studied by Thirunarayanan [31]. Sakthinathan et al., have investigated the effect of substituents on naphthyl based pyrazoline derivatives [32]. Sasikala et al.,[22] have evaluated the effect of substituents and antimicrobial activities of some 5-bromo-2-thienyl based pyrazolines. The spectral correlation of infrared and nuclear magnetic resonance spectra of E-imines have been predicted by Sakthinathan et. al. and Suresh et al.,[33,34]. Thirunarayanan and Sekar have investigated the substituent effects on the IR and NMR spectral frequencies of some 3-(3,4-

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Antitumor Agents. 2. Synthesis, Structure−Activity Relationships, and Biological Evaluation of Substituted 5H-Pyridophenoxazin-5-ones with Potent Antiproliferative Activity

Cited by 56 publications

References 12 publications

Design, synthesis, and biological evaluation of novel pyridine acid esters of podophyllotoxin and esters of 4′-demethylepipodophyllotoxin

Design, synthesis, and biological evaluation of novel pyridine acid esters of podophyllotoxin and esters of 4′-demethylepipodophyllotoxin

Antitumor Agents. 5. Synthesis, Structure−Activity Relationships, and Biological Evaluation of Dimethyl-5H-pyridophenoxazin-5-ones, Tetrahydro-5H-benzopyridophenoxazin-5-ones, and 5H-Benzopyridophenoxazin-5-ones with Potent Antiproliferative Activity

Hammett Spectral Correlations in some Aryl 1,3-Oxazine-4-Thione Derivatives

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