Potent In vitro methicillin-resistant Staphylococcus aureus activity of 2-(1H-indol-3-yl)tetrahydroquinoline derivatives

Hoemann, Michael Z.; Xie, Roger L.; Rossi, Richard F.; Meyer, Sylvia; Sidhu, Alban; Cuny, Gregory D.; Hauske, J. R.

doi:10.1016/s0960-894x(01)00714-4

Cited by 38 publications

(7 citation statements)

References 3 publications

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“…The quinolines (Qs) and their structural analogs are flat aromatic molecules widely distributed in nature that display a wide spectrum of biological activities (Michael, ). Diverse substituted Qs showed therapeutic potential in the treatment of diseases of microbial origin (Urbina et al, ; Buller et al, ; Hoemann et al, ; Jacquemond‐Collet et al, ; Gómez‐Barrio et al, ; Gholap et al, ; Nandhakumar et al, ; Meléndez Gómez et al, ), as well as antitumor (Rodríguez‐Loaiza et al, ; Khan, ; Li et al, ; Loza‐Mejía et al, ) and neuroprotective (Wright et al, ; Di Fabio et al, ) agents. Despite the therapeutic potential of Qs, their use as pharmaceuticals is limited because some of these compounds are carcinogenic in the colon and liver of animal models (Hirao et al, ; Futakuchi et al, ; Saeki et al, ), an effect that has been associated with their mutagenic potency in the corresponding organ (Nagao et al ; Asakura et al, ; Suzuki et al, ).…”

Section: Introductionmentioning

confidence: 99%

Genotoxicity risk assessment of diversely substituted quinolines using the SOS chromotest

Duran

Rincón

Galvis

et al. 2013

Environmental Toxicology

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Quinolines are aromatic nitrogen compounds with wide therapeutic potential to treat parasitic and microbial diseases. In this study, the genotoxicity of quinoline, 4-methylquinoline, 4-nitroquinoline-1-oxide (4-NQO), and diversely functionalized quinoline derivatives and the influence of the substituents (functional groups and/or atoms) on their genotoxicity were tested using the SOS chromotest. Quinoline derivatives that induce genotoxicity by the formation of an enamine epoxide structure did not induce the SOS response in Escherichia coli PQ37 cells, with the exception of 4-methylquinoline that was weakly genotoxic. The chemical nature of the substitution (C-5 to C-8: hydroxyl, nitro, methyl, isopropyl, chlorine, fluorine, and iodine atoms; C-2: phenyl and 3,4-methylenedioxyphenyl rings) of quinoline skeleton did not significantly modify compound genotoxicities; however, C-2 substitution with α-, β-, or γ-pyridinyl groups removed 4-methylquinoline genotoxicity. On the other hand, 4-NQO derivatives whose genotoxic mechanism involves reduction of the C-4 nitro group were strong inducers of the SOS response. Methyl and nitrophenyl substituents at C-2 of 4-NQO core affected the genotoxic potency of this molecule. The relevance of these results is discussed in relation to the potential use of the substituted quinolines. The work showed the sensitivity of SOS chromotest for studying structure-genotoxicity relationships and bioassay-guided quinoline synthesis.

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Section: Introductionmentioning

confidence: 99%

Genotoxicity risk assessment of diversely substituted quinolines using the SOS chromotest

Duran

Rincón

Galvis

et al. 2013

Environmental Toxicology

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“…Mardenborough et al synthesized several N-substituted quindolines to study the effect of N-alkylation on the antimicrobial activity of selected quindolines. The synthesized compounds were evaluated for their antimicrobial activity against selected bacterial and fungal strains including MRSA which indicated that compound 46 was most potent anti-MRSA agent having IC 50 value of 2.0 µg/mL (Table 24) (Table 26) [48].…”

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A review on quinoline derivatives as anti-methicillin resistant Staphylococcus aureus (MRSA) agents

Kumar

2020

BMC Chemistry

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Methicillin Resistant Staphylococcus aureus (MRSA) consists of strains of S. aureus which are resistant to methicillin. The resistance is due to the acquisition of mecA gene which encodes PBP2a unlike of any PBPs normally produced by S. aureus. PBP2a shows unusually low β-Lactam affinity and remains active to allow cell wall synthesis at normally lethal β-Lactam concentrations. MRSA can cause different types of infections like Healthcare associated MRSA, Community associated MRSA and Livestock associated MRSA infections. It causes skin lesions, osteomyelitis, endocarditis and furunculosis.To treat MRSA infections, only a few options are available like vancomycin, clindamycin, co-trimoxazole, fluoroquinolones or minocycline and there is a dire need of discovering new antibacterial agents that can effectively treat MRSA infections. In the current review, an attempt has been made to compile the data of quinoline derivatives possessing anti-MRSA potential reported to date.

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“…1 Primarily, various substituted linear furo [2,3-b]quinolines and angular furo [3,2-c]quinolines have attracted considerable attention as a result of their significant role in medicinal chemistry and their presence in a variety of alkaloids. 2,3 This class of compounds mainly isolated from Rutaceae plant family exhibit antiallergic, 4 anti-inflammatory, 4 cytotoxic, 5 platelet aggregation inhibiting, 5 antimicrobial, 6 voltage-gated potassium channel blocking, 7 spasmolytic, 8 antimalarial, 8 and mutagenic 8 activity. In addition, furoquinolines have a long and successful history in the treatment of Alzheimer's disease.…”

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Robust synthesis of linear and angular furoquinolines using Rap–Stoermer reaction

Kumar

Rajkumar

Rajendran

2016

Chem Heterocycl Comp

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Several naturally occurring compounds and their synthetic analogs containing the quinoline scaffold are known to possess promising pharmacological properties. 1 Primarily, various substituted linear furo [2,3-b]quinolines and angular furo [3,2-c]quinolines have attracted considerable attention as a result of their significant role in medicinal chemistry and their presence in a variety of alkaloids. 2,3 This class of compounds mainly isolated from Rutaceae plant family exhibit antiallergic, 4 anti-inflammatory, 4 cytotoxic, 5 platelet aggregation inhibiting, 5 antimicrobial, 6 voltage-gated potassium channel blocking, 7 spasmolytic, 8 antimalarial, 8 and mutagenic 8 activity. In addition, furoquinolines have a long and successful history in the treatment of Alzheimer's disease. 9 Such diverse types of biological activity have encouraged us to synthesize new linear and angular furoquinolines with different substituents at position 2.Some reports are available in the literature regarding the construction of angular furo[3,2-c]quinolines, such as the synthesis of 5-methylfuro[3,2-c]quinolin-4(5H)-one via Perkin rearrangement of 3-bromo-6-methyl-5,6-dihydro-2H-pyrano[3,2-c]quinoline-2,5-dione, 10 synthesis of 2-alkyl/aryl-4-oxo-4,5-dihydrofuro[3,2-c]quinoline-3-carboxylic acids by treating 3-acyl-4-hydroxy-1H-quinolin-2-ones with ethyl (triphenylphosphoranylidene)acetate, 11 synthesis of 2-alkylfuro[3,2-c]quinolin-4(5H)-ones by reacting 1-alkyl-4-hydroxyquinolin-2(1H)-ones with a number of alkynyl halides, 12 and the synthesis of furo[2,3-c]-condensed 1,2,3,4-tetrahydro-1,10-phenanthrolines from 8-aminoquinolines. 13 These methods required multiple steps and gave low yields. Previously we also reported the synthesis of 2-benzoylfuro[2,3-b]quinolines 14 and 2-acetylfuro[2,3-b]-quinolines. 15 In a continuation of our attempts to access this class of compounds, we herein report an efficient methodology for the synthesis of linear 4-phenylfuro[2,3-b]-quinolines and angular N-methylfuro [3,2-c]quinolines with amide, ester, and ketone groups as substituents at position 2 via the Rap-Stoermer reaction. 16 The Rap-Stoermer reaction has been already applied in the synthesis of linear 2-substituted furo[2,3-b]quinolines by utilizing 3-formyl-2-hydroxyquinolines and α-halocarbonyl compounds. 17 There are no reports available in the literature regarding the reaction of 2-and 4-hydroxy-3-acetylquinolines with α-halocarbonyl compounds to obtain linear and angular furoquinolines in the Rap-Stoermer reaction.We performed the Rap-Stoermer reaction with 3-acetyl-6-chloro-4-phenyl-1H-quinolin-2-one 18 (1) and three different We have synthesized novel linear and angular furoquinolines via the Rap-Stoermer reaction by conventional as well as microwave method that furnished an enhanced yield. Initially, we synthesized linear furo[2,3-b]quinolines from 3-acetyl-6-chloro-4-phenyl-1H-quinolin-2-one and three different α-halocarbonyl compounds: chloroacetophenone, ethyl chloroacetate, and chloroacetamide. The scope of the methodology was furth...

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Potent In vitro methicillin-resistant Staphylococcus aureus activity of 2-(1H-indol-3-yl)tetrahydroquinoline derivatives

Cited by 38 publications

References 3 publications

Genotoxicity risk assessment of diversely substituted quinolines using the SOS chromotest

Genotoxicity risk assessment of diversely substituted quinolines using the SOS chromotest

A review on quinoline derivatives as anti-methicillin resistant Staphylococcus aureus (MRSA) agents

Robust synthesis of linear and angular furoquinolines using Rap–Stoermer reaction

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