Synthesis, molecular docking, antibacterial, antioxidant, and cytotoxicity activities of novel pyrido-cyclopenta[<i>b</i>]indole analogs

Amuthavalli, A.; Prakash, B.; Thirugnanasampandan, Ramaraj; Gogulramnath, Madhusudhanan; Bhuvaneswari, G.; Velmurugan, Rajendran

doi:10.1080/00397911.2020.1733610

Cited by 7 publications

(6 citation statements)

References 43 publications

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“…GSK2018682 has been developed for the treatment of relapsing-remitting multiple sclerosis, and phase 1 trial was completed in 2011 ( Xu et al, 2014 ), however, its development has been discontinued since. GSK2018682 and etrasimod contain indole and cyclopenta[ b ]indole core, respectively, which are considered as promising scaffolds with a broad range of biological activities, including antibacterial effects ( Samosorn et al, 2006 ; Lepri et al, 2016 ; Amuthavalli et al, 2020 ; Chen et al, 2021 ). Finally, AUY954 was shown to prevent transplant rejection in mice ( Pan et al, 2006 ), but to the best of our knowledge, it has not yet reached clinical trials.…”

Section: Resultsmentioning

confidence: 99%

Repurposing the Sphingosine-1-Phosphate Receptor Modulator Etrasimod as an Antibacterial Agent Against Gram-Positive Bacteria

et al. 2022

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New classes of antibiotics are urgently needed in the fight against multidrug-resistant bacteria. Drug repurposing has emerged as an alternative approach to accelerate antimicrobial research and development. In this study, we screened a library of sphingosine-1-phosphate receptor (S1PR) modulators against Staphylococcus aureus and identified five active compounds. Among them, etrasimod (APD334), an investigational drug for the treatment of ulcerative colitis, displayed the best inhibitory activity against S. aureus when growing as free-floating planktonic cells and within biofilms. In follow-up studies, etrasimod showed bactericidal activity and drastic reduction of viable bacteria within 1 h of exposure. It also displayed a potent activity against other Gram-positive bacteria, including penicillin- and methicillin-resistant S. aureus strains, S. epidermidis, and Enterococcus faecalis, with a minimum inhibitory concentration (MIC) ranging from 5 to 10 μM (2.3–4.6 μg/mL). However, no inhibition of viability was observed against Gram-negative bacteria Acinetobacter baumannii, Escherichia coli, and Pseudomonas aeruginosa, showing that etrasimod preferably acts against Gram-positive bacteria. On the other hand, etrasimod was shown to inhibit quorum sensing (QS) signaling in Chromobacterium violaceum, suggesting that it may block the biofilm formation by targeting QS in certain Gram-negative bacteria. Furthermore, etrasimod displayed a synergistic effect with gentamicin against S. aureus, thus showing potential to be used in antibiotic combination therapy. Finally, no in vitro toxicity toward mammalian cells was observed. In conclusion, our study reports for the first time the potential of etrasimod as a repurposed antibacterial compound against Gram-positive bacteria.

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Section: Resultsmentioning

confidence: 99%

Repurposing the Sphingosine-1-Phosphate Receptor Modulator Etrasimod as an Antibacterial Agent Against Gram-Positive Bacteria

et al. 2022

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“…Ключевые слова: циклопента[b]индол, 2.3-аннелирование, циклоприсоединение, тетрагидрокарбазол, циклогепта[b]индол Соединения, имеющие в своем составе структурный элемент циклоалка[b]индола, обнаружены во многих природных алкалоидах [1][2][3][4][5][6][7], а также находят применение при получении синтетических биологически активных веществ [8][9][10] или структурных единиц, сенсибилизированных красителем солнечных элементов [11][12][13], чем и обусловлен высокий интерес к соединениям такого строения [14][15][16][17][18][19].…”

Section: в обзоре обобщены данные о синтезе соединений остовом которы...unclassified

NEW ADVANCES IN THE SYNTHESIS OF CYCLOALKA[b]INDOLS

2023

Izv. Vyssh. Uchebn. Zaved. Khim. Khim. Tekhnol.

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The review summarizes data on the synthesis of compounds whose backbone is a cycloalka[b]indole heterocycle. Approaches to the synthesis of homologous structures are considered, ranging from a carbocyclic fragment with three carbon atoms to eight-membered analogues. Examples of cyclizations are presented, including those with induction of chiral centers using appropriate catalytic systems, with different enantio- and diastereoselectivity. Attention is paid to carbocyclization reactions occurring in the presence of metal complexes, lithium alkylates, inter- or intramolecular cycloaddition of allenes, activated alkenes with 1,3-dipolarophiles or diene-like systems. In the preparation of cycloprop[b]indoles, [2+1]-cycloaddition reactions of indoles with various carbenes are most often used. In approaches to the synthesis of indoles annelated with cyclobutane, [2+2]-cycloaddition reactions are used. To obtain indoles, to which 2,3-annelated carbocycles of medium size, synthetic methods are effectively used, including the use of indole derivatives, 3-nitroindole derivatives as starting materials, intra- and intermolecular reactions of 3-ethynyl-, 3-allenyl -, 3-alkenyl- or functionalized 2-alkyl-substituted indoles in the presence of complexes of palladium, gold, rhodium, copper, silver, indium, organophosphorus acids and their amides, trifluoroethanol, hexafluoroisopropanol, organic sulfo- or trifluoroacetic acids. Methods of photochemical exposure are known, leading to cyclopenta[b]indoles. In the preparation of these heterocycles, cycloaddition reactions of 1,3-dipoles generated from (2-indolyl)diarylmethanols to dipolarophiles are successfully used. Equally effective are cycloaddition reactions of 2-vinylindole derivatives to activated alkenes or carbonyl compounds in the presence of various catalysts, leading to di- or tetrahydrocarbazoles or their seven-membered homologues. One of the frequently used approaches to obtain cycloalka[b]indoles are reactions based on catalyzed transformations of indole-substituted cyclopropanes or intermolecular interaction of cyclopropanes with indoles under various conditions.

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“…Regarding anti-oxidant screening, compounds ( E )-2-cyano-2-(5-methyl-3,4-dihydrocyclopenta[b]indol-1(2 H )-ylidene) acetamide ( 120 ), ( E )-2-(5-chloro-3,4-dihydrocyclopenta[ b ]indol-1(2 H )-ylidene)-2-cyanoacetamide ( 121 ) and ( 118 ) showed a great activity compared with the reference drug. Finally, cytotoxic activity was also evaluated and compounds ( 118 ) and ( 119 ) exhibited interesting cytotoxicity activity [ 166 ]. …”

Section: An Overview Of Heterocycles Containing Nitrogen As Possible mentioning

confidence: 99%

“…Besides, they were subjected to in-vitro anti-bacterial investigation and showed that the compounds with halogen substituent such as 8-chloro-2-methyl-3oxo-2,3,9,10tetrahydropyrido[4′,3′:3,4]cyclopenta [1,2- 121) and (118) showed a great activity compared with the reference drug. Finally, cytotoxic activity was also evaluated and compounds ( 118) and ( 119) exhibited interesting cytotoxicity activity [166].…”

Section: Pharmaceutical Aspects Of Indole Derivativesmentioning

confidence: 99%

Recent investigations into synthesis and pharmacological activities of phenoxy acetamide and its derivatives (chalcone, indole and quinoline) as possible therapeutic candidates

2021

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Graphical abstract Medicinal chemistry can rightfully be regarded as a cornerstone in the public health of our modern society that combines chemistry and pharmacology with the aim of designing and developing new pharmaceutical compounds. For this purpose, many chemical techniques as well as new computational chemistry applications are used to study the utilization of drugs and their biological effects. In the biological interface, medicinal chemistry constitutes a group of interdisciplinary sciences, as well as controlling its organic, physical and computational pillars. Therefore, medicinal chemists working to design an integrated and developing system that portends an era of novel and safe tailored drugs either by synthesizing new pharmaceuticals or to improving the processes by which existing pharmaceuticals are made. It includes researching the effects of synthetic, semi-synthetic and natural biologically active substances based on molecular interactions in terms of molecular structure with triggered functional groups or the specific physicochemical properties. The present work focuses on the literature survey of chemical diversity of phenoxy acetamide and its derivatives (Chalcone, Indole and Quinoline) in the molecular framework in order to get complete information regarding pharmacologically interesting compounds of widely different composition. From a biological and industrial point of view, this literature review may provide an opportunity for the chemists to design new derivatives of phenoxy acetamide and its derivatives that proved to be the successful agent in view of safety and efficacy to enhance life quality.

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Synthesis, molecular docking, antibacterial, antioxidant, and cytotoxicity activities of novel pyrido-cyclopenta[b]indole analogs

Cited by 7 publications

References 43 publications

Repurposing the Sphingosine-1-Phosphate Receptor Modulator Etrasimod as an Antibacterial Agent Against Gram-Positive Bacteria

Repurposing the Sphingosine-1-Phosphate Receptor Modulator Etrasimod as an Antibacterial Agent Against Gram-Positive Bacteria

NEW ADVANCES IN THE SYNTHESIS OF CYCLOALKA[b]INDOLS

Recent investigations into synthesis and pharmacological activities of phenoxy acetamide and its derivatives (chalcone, indole and quinoline) as possible therapeutic candidates

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