Synthesis and antitumor activity of selected 7-alkylidene substituted cephems

Вейнберг, Г.; Vorona, M.; Шестакова, И.; Kanepe, I.; Zharkova, Olga; Mezapuke, R.; Turovskis, I.; Kalvinsh, Ivars; Lukevics, É.

doi:10.1016/s0968-0896(00)00035-3

Cited by 28 publications

(8 citation statements)

References 9 publications

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“…One disadvantage of the b-lactam ring as a drug is its chemical instability; however most of its degradation products are non toxic and appropriate chemical modifications to improve stability can be considered. Although the primary biological targets of b-lactam antibiotics are the transpeptidase penicillin binding proteins, the cytotoxic potential of some b-lactam containing compounds have been reported [31][32][33][34][35] together with activity of some b-lactams as inhibitors of cholesterol absorption [36], prostate specific antigen [37] and tryptase enzyme [38].…”

Section: Introductionmentioning

confidence: 99%

β-Lactam type molecular scaffolds for antiproliferative activity: Synthesis and cytotoxic effects in breast cancer cells

Meegan

Carr

Knox

et al. 2008

Journal of Enzyme Inhibition and Medicinal Chemistry

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A series of novel b-lactam containing compounds are described as antiproliferative agents and potential selective modulators of the oestrogen receptor. The purpose of the study is to evaluate the antiproliferative effects of these compounds on human MCF-7 and MDA MB-231 breast cancer cells. The compounds are designed to contain three aryl ring substituents arranged on the heterocyclic azetidin-2-one (b-lactam), thus providing conformationally restrained analogues of the triarylethylene arrangement exemplified in the tamoxifen type structure. The compounds demonstrated potency in antiproliferative assays against MCF-7 human breast cancer cell line at low micromolar to nanomolar concentrations with low cytotoxicity and moderate binding affinity to the oestrogen receptor. The effect of a number of aryl and amine functional group substitutions on the antiproliferative activity of the b-lactam products was explored and a brief computational structure-activity relationship investigation with molecular simulation was investigated.

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Section: Introductionmentioning

confidence: 99%

β-Lactam type molecular scaffolds for antiproliferative activity: Synthesis and cytotoxic effects in breast cancer cells

Meegan

Carr

Knox

et al. 2008

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…The fragment is a key pharmacophoric component of both penicillin skeleton and a series of modern β‐lactam antibiotics . Moreover, there are many important nonantibiotic uses of 2‐azetidinones: some of them exhibit antiviral and antitumor effect , use for enzyme inhibition , and gene activation . As a consequence, the interest of organic chemists in the synthesis of new β‐lactam derivatives remains high.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of β‐Lactam‐containing Pyrido[3′,2′:4,5]thieno[3,2‐e][1,4]diazepines

Строганова

Vasilin

Kovalenko

et al. 2017

Journal of Heterocyclic Chem

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Novel tricyclic 1,4‐diazepine derivatives – pyrido[3′,2′:4,5]thieno[3,2‐e][1,4]diazepin‐2‐ones – have been synthesized. Azetidin‐2‐one moiety has been incorporated into the 1,4‐diazepine scaffold by [2 + 2]cycloaddition of functionalized ketenes to imine C═N bond, and several tetracyclic azetodiazepines which can be considered as potential compounds of biological interest have been prepared. Stereoselectivity of the cycloaddition was proved by NMR and X‐ray analysis data.

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“…The 1 H NMR spectral data for 3a,c and 4 a,c indicate that their alkylidene substituent has (7Z)-configuration: the singlet for H-9 proton in these compounds is found at 6.6-7.2 ppm and is characteristic for (7Z)-methylidenecephalosporins [2,3]. The signals of the alkylidene substituent protons in 3b and 4b, which can undergo keto-enol tautomerization, are seen as three one-proton singlets at 5.4-5.5, 6.4-6.6, and 11.7-11.8 ppm.…”

mentioning

confidence: 96%

Synthesis and biological activity of alkylidene-substituted cephems and penams

Potoročina

Vorona

Шестакова

et al. 2011

Chem Heterocycl Comp

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rin and penicillin analogs with an alkylidene substituent in the E-lactam ring. Most of these products were oxidized by meta-chloroperbenzoic acid to the corresponding sulfones. The cephemes and penams synthesized including the oxidized products displayed high cytotoxicity relative to cancer cells in vitro. Some of the alkylidene-substituted cephems as the free acids, similar to Tazobactam, inhibit the catalytic activity of Enterobacter cloacae penicillinase. sulfones, condensation, oxidation by m-chloroperbenzoic acid.Continuing a study of the relations between structure and biological activity of cephalosporin and penicillin derivatives [1], we report here the synthesis of new analogs of these antibiotics with an alkylidene substituent in the E-lactam ring as well as their 1,1-dioxo derivatives and the anticancer activity of these compounds in vitro. The effect of the tert-butyl carboxyl protective group on the capacity of some of these cephalosporin and penicillin analogs to inhibit E-lactamase was clarified.The desired tert-butyl esters of 7-alkylidene-3-methyl-1,1-dioxoceph-3-em-4-carboxylic acids 3a-c were synthesized by condensation of the tert-butyl ester of 7-oxo-3-methylceph-3-em-4-carboxylic acid (1) with N-methoxycarbamoyl-N-methylmethylidene-(2a), 3-ethoxycarbonyl-2-oxopropylidene-(2b), and 2-(2-furyl)-2-oxoethylidene(triphenyl)phosphorane (2c), respectively. Products 3a-c were oxidized using meta-chloroperbenzoic acid (MCPBA) to give the corresponding sulfones 4a-c.

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Synthesis and antitumor activity of selected 7-alkylidene substituted cephems

Cited by 28 publications

References 9 publications

β-Lactam type molecular scaffolds for antiproliferative activity: Synthesis and cytotoxic effects in breast cancer cells

β-Lactam type molecular scaffolds for antiproliferative activity: Synthesis and cytotoxic effects in breast cancer cells

Synthesis of β‐Lactam‐containing Pyrido[3′,2′:4,5]thieno[3,2‐e][1,4]diazepines

Synthesis and biological activity of alkylidene-substituted cephems and penams

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