Evaluation of some Mannich bases of conjugated styryl ketones and related compounds versus the WiDr colon cancer in vitro

Dimmock, Jonathan R.; Phillips, Oludotun A.; Wonko, Sheri L; Hickie, Robert A.; Tuer, Robert G; Ambrose, Stephen J.; Reid, R. S.; Mutus, Bülent; Talpas, Christopher J.

doi:10.1016/0223-5234(89)90002-0

Cited by 15 publications

(10 citation statements)

References 11 publications

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“…Determination of log P values. The log P figures were determined by a previously reported procedure except that solutions were made using 1-octanol to which buffer was added. The λ max and ε values of the compounds were obtained in 1-octanol and not phosphate-buffered saline, pH 7.4, due to the low aqueous solubilities of the compounds.…”

Section: Methodsmentioning

confidence: 99%

(Aryloxy)aryl Semicarbazones and Related Compounds: A Novel Class of Anticonvulsant Agents Possessing High Activity in the Maximal Electroshock Screen

et al. 1996

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A number of (aryloxy)aryl semicarbazones and related compounds were synthesized and evaluated for anticonvulsant activities. After intraperitoneal injection to mice, the semicarbazones were examined in the maximal electroshock (MES), subcutaneous pentylenetetrazole (scPTZ), and neurotoxicity (NT) screens. The results indicated that greater protection was obtained in the MES test than the scPTZ screen. Quantitation of approximately one-third of the compounds revealed an average protection index (PI, i.e. TD50/ED50) of approximately 9. After oral administration to rats, a number of compounds displayed significant potencies in the MES screen (ED50 of 1-5 mg/kg) accompanied by very high protection indices. In fact over half the compounds had PI figures of greater than 100, and two were in excess of 300. The compounds were essentially inactive in the scPTZ and NT screens after oral administration to rats. Various compounds displayed greater potencies and PI figures in the mouse intraperitoneal and rat oral screens than three reference clinically used drugs. The data generated supported a binding site hypothesis. Quantitative structure-activity relationships indicated a number of physicochemical parameters which contributed to activity in the MES screen. X-ray crystallography of five compounds suggested the importance of certain interatomic distances and bond angles for activity in the mouse and rat MES screens.

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Section: Methodsmentioning

confidence: 99%

(Aryloxy)aryl Semicarbazones and Related Compounds: A Novel Class of Anticonvulsant Agents Possessing High Activity in the Maximal Electroshock Screen

et al. 1996

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“…This assumption depends on nonequivalent charges at the olefinic bonds in order to avoid synchronous attack at both olefinic carbon atoms. The p K a values of the acyclic Mannich base 7 and related analogues were correlated with the magnititude of the Hammett σ values in the aryl ring . Hence basicity and electron densities of the β-arylvinyl group are interrelated.…”

Section: Introductionmentioning

confidence: 96%

“…Three related analogues were also considered for cytotoxic evaluation. First, 7 (as the hydrobromide salt) has 1.3 times the activity of 5-fluorouracil against the human WiDr colon cancer in vitro, and a comparison of its cytotoxicity with 1b using the screens employed in the present study was of interest. Second, 8a , b were suggested in order to determine the effect of p K a on cytotoxicity.…”

Section: Introductionmentioning

confidence: 99%

4-(β-Arylvinyl)-3-(β-arylvinylketo)-1-ethyl-4-piperidinols and Related Compounds: A Novel Class of Cytotoxic and Anticancer Agents

et al. 1998

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The syntheses of a series of 1-aryl-5-diethylamino-1-penten-3-one hydrochlorides 1 and 1-aryl-3-diethylamino-1-propanone hydrochlorides 4 were accomplished. Attempts to prepare the corresponding bis(5-aryl-3-oxo-4-pentenyl)ethylamine hydrochlorides 2 and bis(3-aryl-3-oxopropyl)ethylamine hydrochlorides 5 led to the formation of a series of 4-(beta-arylvinyl)-3-(beta-arylvinylketo)-1-ethyl-4-piperidi nol hydrochlorides 9 and 4-aryl-3-arylketo-1-ethyl-4-piperidinol hydrochlorides 11, most of which were converted subsequently into the corresponding quaternary ammonium salts 10 and 12, respectively. The structures of these compounds were determined by 1H NMR spectroscopy and confirmed by X-ray crystallography of representative molecules. Most compounds displayed significant cytotoxicity toward murine P388 and L1210 cells as well as human tumors. In general, Mannich bases containing olefinic bonds were more cytotoxic than the analogues without this functional group, while the piperidines 9 and 11 were more potent than the acyclic analogues 1 and 4, respectively. Correlations were noted between various physicochemical constants in the aryl rings and cytotoxicity. Compound 9d displayed promising in vivo activity against colon cancers. This study has revealed that the piperidines 9 and 11 constitute new classses of cytotoxic agents.

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“…Halogen atoms in the para position of the phenyl rings at C4, C5 and Fig. [20,21,24,25,[33][34][35][47][48][49][50][51]. The transition state of the electrophilic attack.…”

Section: Synthesis Of Pyrroles As Antifungal Agentsmentioning

confidence: 99%

“…Briefly, the reaction of 4-methylthio) benzaldehyde with methyl vinyl ketone was shown to be very versatile and high-yielding in the preparation of the 1,4-diketone (33) [69], which was transformed into the corresponding 4methylsulfonyl derivative (33) by means of oxone oxidation [68]. Compound (33), heated in the presence of the appropriate amine, according to the usual Paal-Knorr (thermal) condensation, cyclized to yield the expected 3-unsubstituted 1,5diarylpyrrole (34) in satisfactory yield after prolonged reflux. The construction of the acetic acid chain was achieved by regioselective acylation [71] of (34) with ethoxalyl chloride in the presence of pyridine to give derivatives (31a-c).…”

Section: Bm 212mentioning

confidence: 99%

New Pyrroles with Potential Antimycobacterial, Antifungal and Selective COX-2 Inhibiting Activities. Synthetic Methodologies

Biava¹,

Porretta²,

Poce³

et al. 2007

COC

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Tuberculosis (TB) and fungal diseases are opportunistic infections that very often complicate the immunological response in HIV-infected individuals [1][2][3]. During our studies on novel antimycobacterial and antifungal agents we synthesized a number of new pyrrole derivatives and among them some proved very active against both fungi and mycobacteria. Some others instead were very selective against mycobacteria only. So we pursued a program aimed at individuating the chemical groups or their association, responsible for the particular activity. Moreover, many other pyrroles we synthesized showed to be very active as COX-2 selective inhibitors. In this review we describe our approaches to the synthesis of the pyrrolic structures studied. N CH 3 N N C H 3 Cl Cl N Cl H NO 2 Cl

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Evaluation of some Mannich bases of conjugated styryl ketones and related compounds versus the WiDr colon cancer in vitro

Cited by 15 publications

References 11 publications

(Aryloxy)aryl Semicarbazones and Related Compounds: A Novel Class of Anticonvulsant Agents Possessing High Activity in the Maximal Electroshock Screen

(Aryloxy)aryl Semicarbazones and Related Compounds: A Novel Class of Anticonvulsant Agents Possessing High Activity in the Maximal Electroshock Screen

4-(β-Arylvinyl)-3-(β-arylvinylketo)-1-ethyl-4-piperidinols and Related Compounds: A Novel Class of Cytotoxic and Anticancer Agents

New Pyrroles with Potential Antimycobacterial, Antifungal and Selective COX-2 Inhibiting Activities. Synthetic Methodologies

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