One-Pot Synthesis of N-Fused Quinolone-4 Tetracyclic Scaffolds from 2,2-Disubstituted Indolin-3-ones DOI Creative Commons
Nikolai A. Arutiunov, Anna M. Zatsepilina, Anna A. Aksenova

et al.

ACS Omega, Journal Year: 2024, Volume and Issue: 9(45), P. 45501 - 45517

Published: Oct. 29, 2024

A cascade transformation of C2-quaternary indoxyls leading to an efficient assembly complex (dihydro)indolo[1,2-a]quinolin-5-one ring systems is reported. The method involves the gram-scale preparation 2-(2-aryl-3-oxoindolin-2-yl)-2-phenylacetonitriles which are then converted with methyl ketones corresponding 2-(2-oxo-2-aryl(alkyl)ethyl)-2-phenylindolin-3-ones. latter can either be isolated good yields (75–96%) or, in case o-nitroacetophenone, used situ for further base-assisted intramolecular SNAr cyclization resulting indoxyl-fused quinolone-4 hybrids (up 95%).

Language: Английский

Regiodivergent Ring-Expansion of Oxindoles to Quinolinones DOI Creative Commons

Hendrik L. Schmitt,

Den Martymianov,

Ori Green

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(7), P. 4301 - 4308

Published: Feb. 9, 2024

The development of divergent methods to expedite structure–activity relationship studies is crucial streamline discovery processes. We developed a rare example regiodivergent ring expansion access two regioisomers from common starting material. To enable this regiodivergence, we identified distinct reaction conditions for transforming oxindoles into quinolinone isomers. presented proved be compatible with variety functional groups, which enabled the late-stage diversification bioactive as well facilitated synthesis drugs and their derivatives.

Language: Английский

Citations

20
Multifunctional antibacterial hydrogels for chronic wound management DOI Creative Commons

Yungang Hu,

Yu Lu, Qiang Dai

et al.

Biomaterials Science, Journal Year: 2024, Volume and Issue: 12(10), P. 2460 - 2479

Published: Jan. 1, 2024

Due to their distinctive physical and chemical properties as well biological functionalities, multifunctional antibacterial hydrogels possess significant advantages in the treatment of chronic wounds.

Language: Английский

Citations

12
Antibiotics: From Mechanism of Action to Resistance and Beyond DOI
Shyamalima Saikia, Pankaj Chetia

Indian Journal of Microbiology, Journal Year: 2024, Volume and Issue: 64(3), P. 821 - 845

Published: April 29, 2024

Language: Английский

Citations

12
Cu-Catalyzed Tandem C–N and C–C Bond Formation Leading to 4(1H)-Quinolones: A Scaffold with Diverse Biological Properties from Totally New Raw Materials in a Single Step DOI
Satyanarayana Tummanapalli,

Kali Charan Gulipalli,

Srinu Bodige

et al.

The Journal of Organic Chemistry, Journal Year: 2024, Volume and Issue: 89(3), P. 1609 - 1617

Published: Jan. 18, 2024

A novel Cu-catalyzed tandem C–N and C–C bond-formation reaction has been developed to furnish 2-substituted-4-(1H)-quinolones. 4-(1H)-quinolones play an important role in medicinal chemistry. Many 2-aryl(alkyl)-4(1H)-quinolones are found exhibit diverse biological properties. While traditional methods have inherent issues [like starting materials with incompatible functional groups (NH2 keto groups)], many modern either require activated (like Ynones) or employ expensive metals (Pd, Rh, Au, etc.) involving carbonylation using CO metal complexes. Our protocol presents environmentally friendly one-step method for the construction of these useful 2-substituted-4-(1H)-quinolones from easily available aryl boronic acid (or pinacolate ester) nitriles as new raw materials, a cheap Cu-catalyst O2 (air) green oxidant. We further extended its application synthesis various natural products, including first formal total punarnavine. plausible mechanism nitrilium ion (formed due intermolecular bond-forming coupling between boron species nitrile group) followed by intramolecular bond formation proposed.

Language: Английский

Citations

7
Fluoroquinolones tackling antimicrobial resistance: Rational design, mechanistic insights and comparative analysis of norfloxacin vs ciprofloxacin derivatives DOI

Aanchal Khanna,

Nitish Kumar,

Rupali Rana

et al.

Bioorganic Chemistry, Journal Year: 2024, Volume and Issue: 153, P. 107773 - 107773

Published: Sept. 3, 2024

Language: Английский

Citations

7
Bioisosteric heterocyclic analogues of natural bioactive flavonoids by scaffold-hopping approaches: State-of-the-art and perspectives in medicinal chemistry DOI Creative Commons
Gabriele La Monica, Alessia Bono, Federica Alamia

et al.

Bioorganic & Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 109, P. 117791 - 117791

Published: June 9, 2024

The flavonoid family is a set of well-known bioactive natural molecules, with wide range potential therapeutic applications. Despite the promising results obtained in preliminary vitro/vivo studies, their pharmacokinetic and pharmacodynamic profiles are severely compromised by chemical instability. To address this issue, scaffold-hopping approach strategy for structural optimization leads to discover more potent analogues. In scenario, Perspective provides critical analysis on how replacement chromon-4-one core other bioisosteric nitrogen/sulphur heterocycles might affect chemical, pharmaceutical biological properties resulting new entities. investigated derivatives were classified basis activity indications. For each session, target(s), specific mechanism action, if available, key pharmacophoric moieties highlighted, as revealed X-ray crystal structures silico structure-based studies. Biological data, examined: particular focus was given improvements observed heterocyclic analogues compared flavonoids. This overview advantages compounds great interest medicinal chemistry community better exploit vast these molecules identify molecules.

Language: Английский

Citations

6
Skeletal Editing of Isatins for Heterocycle Molecular Diversity DOI
Tiantian Zhang, Huangdi Feng

The Chemical Record, Journal Year: 2024, Volume and Issue: 24(6)

Published: June 1, 2024

Isatins have been widely used in the preparation of a variety heterocyclic compounds, where skeletal editing isatins has shown significant advantages for construction diverse heterocycles. This review highlights progress made last decade (2013-2023) isatin scaffold. A series ring expansion reactions quinoline skeleton, quinolone polycyclic quinazoline medium-sized as well opening generation 2-(azoly)aniline skeleton by cleavage C-C bond and C-N are highlighted. It is hoped that this will provide some understanding chemical transformations contribute to further realization its molecular diversity.

Language: Английский

Citations

5
Fluoroquinolones and Biofilm: A Narrative Review DOI Creative Commons
Nicholas Geremia, F Giovagnorio, Agnese Colpani

et al.

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(12), P. 1673 - 1673

Published: Dec. 11, 2024

Background: Biofilm-associated infections frequently span multiple body sites and represent a significant clinical challenge, often requiring multidisciplinary approach involving surgery antimicrobial therapy. These are commonly healthcare-associated related to internal or external medical devices. The formation of biofilms complicates treatment, as they create environments that difficult for most agents penetrate. Fluoroquinolones play critical role in the eradication biofilm-related infections. Numerous studies have investigated synergistic potential combining fluoroquinolones with other chemical augment their efficacy while minimizing toxicity. Comparative research suggests antibiofilm activity is superior beta-lactams glycopeptides. However, remains less effective than minocycline fosfomycin. Noteworthy combinations include fosfomycin aminoglycosides enhanced against Gram-negative organisms rifampin more treatment Gram-positive Despite limitations due intrinsic characteristics this antibiotic, remain fundamental setting thanks bioavailability synergisms drugs. Methods: A comprehensive literature search was conducted using online databases (PubMed/MEDLINE/Google Scholar) books written by experts microbiology infectious diseases identify relevant on biofilm. Results: This review critically assesses managing biofilm-associated various settings also exploring benefits combination therapy these antibiotics. Conclusions: predominantly consists vitro studies, limited vivo investigations. Although real world data scarce, accordance fluoroquinolones’ effectiveness early Also, future perspectives newer options be placed alongside discussed. underscores infections, providing guide physicians regarding best use class antibiotics highlighting existing issues.

Language: Английский

Citations

5
A QSPR analysis and curvilinear regression models for various degree-based topological indices: Quinolone antibiotics DOI Creative Commons

B. Kirana,

M. C. Shanmukha,

A. Usha

et al.

Heliyon, Journal Year: 2024, Volume and Issue: 10(12), P. e32397 - e32397

Published: June 1, 2024

Topological indices play an essential role in defining a chemical compound numerically and are widely used QSPR/QSAR analysis. Using this analysis, physicochemical properties of the compounds topological studied. Quinolones synthetic antibiotics employed for treating diseases caused by bacteria. Across years, have shifted its position from minor drug to very significant treat infections bacteria urinary tract. A study is carried out on various Quinolone antibiotic drugs computing through QSPR Curvilinear regression models such as linear, quadratic cubic determined all indices. These depicted graphically extending fourth degree fifth with corresponding physical property showing variation between each model. Various studies been using linear while work extended curvilinear novel concept finding minimal RMSE. RMSE measure find potential predictive index that fits QSAR/QSPR The goal lies predicting certain based molecular structure.

Language: Английский

Citations

4
Tractable Quinolone Hydrazides Exhibiting Sub‐Micromolar and Broad Spectrum Antitrypanosomal Activities DOI Creative Commons

Kgothatso A. Chirwa,

Karol R. Francisco, Phelelisiwe S. Dube

et al.

ChemMedChem, Journal Year: 2024, Volume and Issue: 19(9)

Published: Feb. 8, 2024

Abstract Nagana and Human African Trypanosomiasis (HAT), caused by (sub)species of Trypanosoma , are diseases that impede human animal health, economic growth in Africa. The few drugs available have drawbacks including suboptimal efficacy, adverse effects, drug resistance, difficult routes administration. New needed. A series 20 novel quinolone compounds with affordable synthetic was made evaluated vitro against brucei HEK293 cells. Of the compounds, 12 had sub‐micromolar potencies parasite (EC 50 values=0.051–0.57 μM), most were non‐toxic to cells (CC values>5 μM). Two potent presented activities other trypanosome ( T. cruzi b. rhodesiense ). Although aqueous solubility is poor, both possess good logD values (2–3), either robust or poor microsomal stability profiles. These varying attributes will be addressed future reports.

Language: Английский

Citations

3