Synthesis and Antibacterial Activity of New N-[2-(Thiophen-3-yl)ethyl] Piperazinyl Quinolones

Letafat, Bahram; Emami, Saeed; Mohammadhosseini, Negar; Faramarzi, Mohammad Ali; Samadi, Nasrin; Shafiee, Abbas; Foroumadi, Alireza

doi:10.1248/cpb.55.894

Cited by 38 publications

(18 citation statements)

References 15 publications

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“…The introduction of the following 4,5,6-membered nitrogencontaining heterocycles is favorable: piperazinyl [3], bicycles [13,97], pyrrolidinyl, piperidinyl [55,60,112], piperazinyl [60]. They, in turn, can contain various bulky substituents (2-(2-furyl)-and 2-(3-thienyl)-2-oxoethyl, hydroxyiminoethyl [102,116], 1,3,4-thiadiazol-2-yl [103][104][105]). Compounds with cyclopropyl, 1-aminocyclopropyl, vinyl, aminomethyl [80], and amino-tert-butyl [64] substituents exhibit excellent activity [13].…”

Section: Methodsmentioning

confidence: 99%

“…The papers belonging to this section mostly relate to the synthesis of derivatives containing a variously substituted piperazine ring at position 7. The required substituent is inserted into the piperazine group by treating the 4-quinolones 123 with the respective bromine derivative in the presence of a base, leading to the derivatives 124a-c [36,102,73]. The 4-quinolone 124c then reacts with isonicotinohydrazide with the formation of compound 125 [36].…”

Section: Insertion Of a Substituent At Position 7 With The Formation mentioning

confidence: 99%

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The methods of synthesis, modification, and biological activity of 4-quinolones (review)

Boteva

Красных

2009

Chem Heterocycl Comp

109

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Data on methods for the construction of the 4-quinolone skeleton and modification of the substituents around it are reviewed. The "structure-activity" relationships of 4-quinolones are examined with respect to antibacterial and antitumor activity.Keywords: 4-quinolones, biological activity. 4-Quinolones have been a subject of research for many scientific teams, and this is reflected in the numerous reviews and monographs devoted to various aspects of the subject. One of the early reviews [1] concerns aspects of the synthesis of individual representatives of the group of 4-quinolones and comparative characterization of their antimicrobial activity. Basic approaches to construction of the fluoroquinolone skeleton and also variation of the substituents at various positions of the ring were examined in the review [2]. The relationship between the structure and antibacterial activity is discussed in [3], and methods for the synthesis of polycyclic derivatives of 4-quinolones based on the annelation of rings to the various faces of the quinoline skeleton are discussed in the review [4]. The reviews [5, 6] were devoted to identification of the structural modifications of 4-quinolones responsible for their conversion from antibacterial agents to antitumor agents. The molecular and biological aspects of the antibacterial action of 4-quinolone-3-carboxylic acids are examined in [7], and issues concerned with the clinical application of 4-quinolones are discussed in the reviews [8][9][10][11][12] and in the monograph [13]. The synthesis and the "structure-activity" relationships of the bioisosteres of 4-quinolones -2-pyridones -are examined in the review [14].The aim of the present review was to classify existing methods for the synthesis not only of fluoroquinolones but also of any 4-quinolones, to demonstrate the effects of modification of the molecule at all positions, to summarize data on the various types of activity, and to examine the "structure-activity" relationship with respect to antibacterial and antitumor activity.

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Section: Methodsmentioning

confidence: 99%

Section: Insertion Of a Substituent At Position 7 With The Formation mentioning

confidence: 99%

The methods of synthesis, modification, and biological activity of 4-quinolones (review)

Boteva

Красных

2009

Chem Heterocycl Comp

109

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“…1 H-NMR spectroscopy is generally used to assign the (E)-and (Z)-geometry of oximes [20,21]. Surveying similar oximes (chroman-4-one oxime systems) suggests that the proximity of the C-5 proton to the oxygen of the oxime in the a-syn configuration will deshield the proton [22,23].…”

Section: Chemistrymentioning

confidence: 99%

Conformationally Constrained Analogs of N‐Substituted Piperazinylquinolones: Synthesis and Antibacterial Activity of N‐(2,3‐Dihydro‐4‐hydroxyimino‐4H‐1‐benzopyran‐3‐yl)‐piperazinylquinolones

Emami

Foroumadi

Samadi

et al. 2009

Archiv der Pharmazie

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A series of novel quinolone agents bearing a particular bulky and conformationally constrained bicyclic substituent (2,3-dihydro-4-hydroxyimino-4H-1-benzopyran-3-yl- moiety) on the piperazine ring of 7-piperazinyl quinolones (norfloxacin, enoxacin, ciprofloxacin, and levofloxacin) were synthesized and evaluated against a panel of Gram-positive and Gram-negative bacteria. Among these derivatives, ciprofloxacin counterpart 9c, highly inhibited the tested Gram-positive bacteria, superior to that of the reference drugs, and displayed antibacterial activity at non-cytotoxic concentrations.

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“…[9] More specifically, substituted heterocyclic benzo [b]thiophenes, quinolones and carboxamides as very important organic structural motifs, have therefore recently attracted considerable attention from medicinal and synthetic organic chemists due to their spectra of diverse pharmacological features. [10][11][12][13] Furthermore, abovementioned structural units could be found in a variety of bioactive natural products and numerous of synthetic medical and biochemical agents. As a part of our continuing search for potential anticancer agents structurally related to heterocyclic quinolones, we have previously reported synthesis and strong inhibitory activities on several human tumor cell lines of versatile benzothiophene and thienothiophene carboxanilides and quinolones, thus confirming the anticancer potential of this class of compounds.…”

Section: Introductionmentioning

confidence: 99%

Comparison of Antitumor Activity of Some Benzothiophene and Thienothiophene Carboxanilides and Quinolones in 2D and 3D Cell Culture System

et al. 2017

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One of the main reasons for the high drug attrition rate in oncology is the poor clinical predictive power of 2D cancer cell lines cultures in vitro which are the standard assay used as screening assay to select new chemical entities (NKE) with potent anticancer activity. Therefore, there is increasing interest in developing 3D in vitro cell culture systems, as a primary screening assays which would represent a biologically more relevant assay system, due to similarity to physiological conditions in which tumors growth in living organism. Very important is to develop reproducible 3D cell line culture in vitro assays, feasible for the primary screening of NKEs platforms. Within this manuscript we have tested small platform of selected benzo [b]thieno, thieno [2,3-b]thiophene, and thieno[3,2-b]thiophene 2-carboxanilides, as well as their cyclic derivatives [2,3-c]quinolones, which already showed anti-proliferative activity on other cancer cell lines in 2D system. Platform was tested in 2D and 3D cancer cell culture assays on three human breast cancer cell lines (SK-BR-3, MDA-MB-231, T-47D). Those cell lines were selected on the basis of ability to growth and form cell spheres and also on different sensitivity to chemotherapeutic agents. We used doxorubicin as control compound due similar mode of action, (specific intercalation with the DNA double helix), as tested compound probably have.Obtained results in some cases showed significant disagreement, indicating that in early screening selection of active compounds only on 2D activity basis we could pick up false positive compounds (active only on 2D cell culture lines and not on 3D cell lines for which it is clamed that are more similar to real physiological conditions for tumor growth). One possibility for obtained discrepancy of results obtained on 2D and 3D cell cultures could be physico-chemical properties of compounds. Therefore, we analyzed some physico-chemical properties of active compounds as chrom logD values and calculated structural parameters: number of hydrogen bond donors and acceptors, calculated logP and logD values, molecular weight, ionization constants (pKa), number of aromatic rings, number of rotatable bonds and polar surface area. Association of physico-chemical descriptors with observed anti-proliferative activity has been investigated. Basicity, molecular weight and number of H-bond donors are found to be main factors contributing to the anti-proliferative effect of investigated compounds for both 2D and 3D cell cultures.

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Synthesis and Antibacterial Activity of New N-[2-(Thiophen-3-yl)ethyl] Piperazinyl Quinolones

Cited by 38 publications

References 15 publications

The methods of synthesis, modification, and biological activity of 4-quinolones (review)

The methods of synthesis, modification, and biological activity of 4-quinolones (review)

Conformationally Constrained Analogs of N‐Substituted Piperazinylquinolones: Synthesis and Antibacterial Activity of N‐(2,3‐Dihydro‐4‐hydroxyimino‐4H‐1‐benzopyran‐3‐yl)‐piperazinylquinolones

Comparison of Antitumor Activity of Some Benzothiophene and Thienothiophene Carboxanilides and Quinolones in 2D and 3D Cell Culture System

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