Quinolone: a versatile therapeutic compound class

Abstract

The discovery of nalidixic acid is one pinnacle in medicinal chemistry, which opened a new area of research that has led to the discovery of several life-saving antimicrobial agents (generally referred to as fluoroquinolones) for over decades. Although fluoroquinolones are frequently encountered in the literature, the utility of quinolone compounds extends far beyond the applications of fluoroquinolones. Quinolone-based compounds have been reported for activity against malaria, tuberculosis, fungal and helminth infections, etc. Hence, the quinolone scaffold is of great interest to several researchers in diverse disciplines. This article highlights the versatility of the quinolone pharmacophore as a therapeutic agent beyond the fluoroquinolone profile. Graphical abstract

Quinolone-3-amidoalkanol: A New Class of Potent and Broad-Spectrum Antimicrobial Agent

“…Compound 10 showed the best solubility of 25 μM within this series, while N -benzylated analogues all had aqueous solubility < 5 μM. It is important to mention that poor solubility has been an issue reported for other quinolone lead compounds in different clinical indications …”

“…It is important to mention that poor solubility has been an issue reported for other quinolone lead compounds in different clinical indications. 32 The compounds generally showed poor permeability of <−6 Log P app in parallel artificial membrane assay (PAMPA). This result could be partly attributed to the poor aqueous solubility of these compounds since the PAMPA is carried out 33 The metabolic stability of the selected compounds was determined in the presence of human, rat, and mouse liver microsomes.…”

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

“…4-Quinolone is a ubiquitous structural feature that appears in numerous natural products and bioactive synthetic compounds possessing diverse pharmacological properties. , Since the accidental discovery of nalidixic acid as a first-generation 4-quinolone-based antibiotic in 1962, a vast variety of biologically active 4-quinolones have been discovered, leading to the development of several life-saving antibacterial agents. , It is estimated that 4-quinolones are the third most prescribed drug for treating various pathogenic infections worldwide. In addition to their antibacterial properties, 4-quinolone-based compounds have been reported to exhibit many other biological activities, thus gaining the “most privileged pharmacophore” status. , The emergence of drug-resistant pathogens is a major concern in the current world, and 4-quinolone continues to play a key role in promising new-generation antibiotics with greater potency by simple structural modifications of the existing versions or developing totally newer 4-quinolones. Among such modifications, 2-substituted-4-(1 H )-quinolone is an important structural variation of 4-quinolone that promises several new biological properties (Figure ).…”

Novel Two-Step Synthesis of N-Alkylated 2,3-Diaryl-4-quinolones

“…1,2 Figure 1 Representatives of 4th generation antimicrobial fluoroquinolone-based drugs Meanwhile, apart from antimicrobial properties, the fluoroquinolones themselves as well as the other 4-quinolones, both naturally occurring and synthetic, have been reported to possess a diverse range of biological activities among which antiviral, antiparasitic, antifungal, and neuroprotective are just a few. [3][4][5] Thus, for instance, the plant-derived alkaloid graveoline 6 along with a number of the sub-stituted 2-phenyl-4-quinolones 1 (Figure 2) have been shown as promising anticancer agents [7][8][9] targeting different pathways (including apoptotic and autophagic) in many human tumor cell lines. Although scattered and often contradictory, accumulated data [10][11][12] and structure-activity relationship studies (SAR) 13 suggest that the antitumor activity of 2-phenyl-4-quinolones 1 is likely not attributed to a single position and originated in a combination of different substituents.…”

“…Several reviews summarizing the recent advances in those areas have been published over the past few years. [3][4][5][15][16][17][18][19][20] Yet, speaking specifically about the synthesis of the 2,3-diaryl-4-quinolones, the choice is narrowed down mainly to two options. The first is a multistep approach (Scheme 2) based on the works of Mphahlele et al [21][22] It would involve various both thermally-activated [23][24][25][26] and transition-metal-catalyzed [27][28][29][30] cyclocondensation methods (Scheme 2a and 2b, Scheme 1, respectively) to construct 2aryl-4-quinolone framework 4 followed by sequential C3halogenation 21,[31][32][33][34] and Suzuki-Miyaura cross-coupling 21,27,31,35 reactions (Scheme 2c) to get the target quinolone 5.…”