Synthesis, anti-tuberculosis activity and QSAR study of 2,4-diarylquinolines and analogous polycyclic derivatives

Muscia, Gisela Celeste; Carnevale, Juan P.; Luczywo, Ayelen; Peláez, María Victoria; Toole, Ailen Rodríguez Ó; Buldain, Graciela; Casal, Juan José; Asís, Silvia Elizabeth

doi:10.1016/j.arabjc.2018.10.003

Cited by 8 publications

(7 citation statements)

References 37 publications

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“…The cyclopenta[b]quinoline (78a) and the acridine derivative (78b-c) had remarkable MIC values (73.41, 44.35, and 61.93 µM, respectively) against the rifampin resistant strain and new tricyclic analogs with lower toxicity toward macrophages and improved antituberculosis activity. The Friedländer syntheses of polycyclic quinoline derivatives as antituberculosis agents were reported in the same group (Muscia et al, 2019). The polycyclic quinoline derivatives (81, 82, 85, 86, 88, 91, and 92) were prepared as analogous of lead compounds from 78a-c (Scheme 17).…”

Section: S C H E M Ementioning

confidence: 99%

Friedlӓnder's synthesis of quinolines as a pivotal step in the development of bioactive heterocyclic derivatives in the current era of medicinal chemistry

et al. 2022

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In the current scenario of medicinal chemistry, quinoline plays a pivotal role in the design of new heterocyclic compounds with several pharmacological properties, so the search for new synthetic methodologies and their application in drug discovery has been widely studied. So far, many procedures have been performed for the preparation of quinoline scaffolds, among which Friedländer quinoline synthesis plays an important role in obtaining these heterocycles. The Friedländer reaction involves condensation between 2‐aminobenzaldehydes and keto‐compounds. The quinoline nucleus, once obtained through the Friedländer synthesis, has been extensively modified so that these derivatives can exhibit a large number of biological activities such as anticancer, antimalarial, antimicrobial, antifungal, antituberculosis, and antileishmanial properties. In this work, the focus is on the applicability of the Friedländer reaction in the synthesis of various types of bioactive heterocyclic quinoline compounds, which to date has not been reported in the context of medicinal chemistry. The main part of this review selectively focuses on research from 2010 to date and will present highlights of the Friedländer quinoline synthesis procedures and findings to address biological and pharmacological activities.

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Section: S C H E M Ementioning

confidence: 99%

Friedlӓnder's synthesis of quinolines as a pivotal step in the development of bioactive heterocyclic derivatives in the current era of medicinal chemistry

et al. 2022

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“…Further, cytotoxic studies were carried out, which led to the identification of highly potent compound 52 , which had higher MIC values (Figure 17) as compared to reference drugs. [ 67 ]…”

Section: Anti‐infective Potential Of 4‐substituted Quinolinesmentioning

confidence: 99%

“…Further, cytotoxic studies were carried out, which led to the identification of highly potent compound 52, which had higher MIC values (Figure 17) as compared to reference drugs. [67] Shruthi et al reported the multistep synthesis of new series of quinoline derivatives bearing 1,2,4-oxadiazole moiety and evaluated them for antitubercular activity against M. tuberculosis using the broth microdilution method using isoniazid (INH) and rifampicin (RIF) as standard positive control drug. Among the tested derivatives, compound 52a with MIC = 0.5 µg/ml while compounds 52b-d with MIC value of 0.25 µg/ml were proved as highly potent antitubercular agents (Figure 17).…”

Section: -Substituted Quinoline As Antitubercular Agentsmentioning

confidence: 99%

Spotlight on 4‐substituted quinolines as potential anti‐infective agents: Journey beyond chloroquine

Goyal

Kharkwal

Piplani

et al. 2022

Archiv der Pharmazie

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Continued emerging resistance of pathogens against the clinically approved candidates and their associated limitations continuously demand newer agents having better potency with a more suited safety profile. Quinoline nuclei containing scaffolds of natural and synthetic origin have been documented for diverse types of pharmacological activities, and a number of drugs are clinically approved. In the present review, we unprecedentedly covered the biological potential of 4-substituted quinoline and elaborated a rationale for its special privilege to afford the significant number of approved clinical drugs, particularly against infectious pathogens. Compounds with 4-substituted quinoline are well documented for antimalarial activity, but in the last two decades, they have been extensively explored for activity against cancer, tuberculosis, and several other pathogens including viruses, bacteria, fungi, and other infectious pathogens. In the present study, the anti-infective spectrum of this scaffold is discussed against viruses, mycobacteria, malarial parasites, and fungal and bacterial strains, along with recent updates in this area, with special emphasis on the structure-activity relationship.

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“…Although initially targeted as antimalarial agents, the design was focused on anti‐TB activity, inspired by natural active alkaloids [8] . The discovery of bedaquiline ( 1 ) and its approval by the FDA was the driving force to design new 2,4‐diarylquinolines ( N ‐(5‐methylisoxazol‐3‐yl)‐2,4‐diphenylquinoline‐6‐sulfonamide, ( 2 ) and 2‐aryl‐4‐quinolinecarboxylic acids (2‐(phenanthren‐3‐yl)quinoline‐4‐carboxylic acid, ( 3 ) [9] as well as polycyclic and fused quinolones (7‐nitro‐9‐phenyl‐1,2,3,4‐tetrahydroacridine, ( 4 ), Figure 1). [8] …”

Section: Introductionmentioning

confidence: 99%

QSAR‐Guided Study for the Microwave‐Assisted Synthesis of 4‐Methylquinoline Derivatives with Antimycobacterial Activity

et al. 2023

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Tuberculosis was discovered more than a century ago, and it is still a disease that presents difficulties in its treatment due to the appearance of new resistant strains. To design new antituberculosis agents with a quinoline structure, our group developed three‐dimensional structure‐activity relationship (3D‐QSAR) models, based on Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Index Analysis (CoMSIA). Statistically robust models (q2>0.6; r2ncv>0.8; r2pred>0.7) and with good external predictability were obtained. We found that positions 2, 3, and 4 of the quinoline nucleus are directly related to the modulation of the growth inhibitory activity of Mycobacterium tuberculosis H37Rv. To validate the models, we synthesized twelve quinolines through the Friëdlander reaction and three indolinones. The synthesized compounds were evaluated in the growth inhibition of resistant H37Rv tuberculosis strains (rpoBS450L, katGdel, and gyrAD94K) and in nontuberculous strains (M. avium and M. abscessus). We found that the compound (Z)‐4‐((2‐oxoindolin‐3‐ylidene)amino)‐N‐(thiazol‐2‐yl)benzenesulfonamide was active in all resistant strains; the compound 2‐(1H‐indol‐3‐yl)‐4‐methylquinoline was active on M. avium; and the compound 10‐methyl‐11H‐indeno[1,2‐b]quinoline was active on M. abscessus. These models are useful for the discovery of new compounds with inhibitory properties of M. tuberculosis H37Rv, and with potential applications in resistant and nontuberculous strains.

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Synthesis, anti-tuberculosis activity and QSAR study of 2,4-diarylquinolines and analogous polycyclic derivatives

Cited by 8 publications

References 37 publications

Friedlӓnder's synthesis of quinolines as a pivotal step in the development of bioactive heterocyclic derivatives in the current era of medicinal chemistry

Friedlӓnder's synthesis of quinolines as a pivotal step in the development of bioactive heterocyclic derivatives in the current era of medicinal chemistry

Spotlight on 4‐substituted quinolines as potential anti‐infective agents: Journey beyond chloroquine

QSAR‐Guided Study for the Microwave‐Assisted Synthesis of 4‐Methylquinoline Derivatives with Antimycobacterial Activity

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