Dual anti‐inflammatory and antiglycation propensities of a potentially novel class of functionalized fluoroquinolones

Abstract

Promoted by elevated blood glucose concentrations in diabetes, glycation involves the nonenzymatic addition of reducing sugars and/or their reactive degradation products to amine groups on proteins. New synthetic approaches to 18 fluoroquinolones (FQs) have been developed on the basis of a promising antiglycation activity using 400μM methylglyoxal as the choice glucocytotoxicity concentration. Their anti-inflammatory and radical scavenging properties were elucidated in vitro. Intriguingly, FQs could exhibit an exceedingly more superior than or substantially comparable cytoprotection against methylglyoxal-induced carbonyl toxicity in RAW264.7 macrophages and antiglycation activity to aminoguanidine, as the reference compound. This kind of activity can suggestively be associated with the chelating properties possessed by the synthesized FQs as their DPPH radical scavenging activities proved to be significantly inferior to those of the reference compound, the ascorbic acid. The inhibitory bioactivities using the Griess assay were examined of the compounds against lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7 macrophages. Selectively, compounds R-2TCBA, R-4FACBA, R-3TCBA, and R-4CLACBA exerted an exceedingly remarkable and superior anti-inflammatory effects (P < .001 vs indomethacin IC 50 value of 101.07 ± 2.2 μM) while R-4TCBA and T-4BrACBA were moderately more efficacious than indomethacin. Compounds T-4CLACBA and R-4BrACBA displayed comparable activity with indomethacin. None of the tested compounds and indomethacin exerted any cytotoxicity against RAW 264.7 mouse macrophages. FQs possess potent duality of antiglycation-anti-inflammatory capacities and are devoid of undesirable side effects. FQs can, therefore, serve as scaffolds for the development and designing of new clinical deglycation and antiglycation therapeutic agents.

Preparation and Characterization of Rutin-Encapsulated Polymeric Micelles and Studies of Synergism with Bioactive Benzoic Acids and Triazolofluoroquinolones as Anticancer Nanomedicines

“…In contrast to other radical scavenging assays, a DPPH radical is stable and Belgium) containing 10% FBS, HEPES Buffer (10 mM), L-glutamine (2 mM), gentamicin (50 µg/mL), penicillin (100 U/mL), and streptomycin sulfate (100 mg/mL). As a robust and classical antineoplastic apoptogenic reference agent (El-Hamoly et al, 2017), cisplatin (1-200 μM) was recruited for comparison purposes (Sweidan et al, 2017 ;Alabsi et al, 2018;Mamdooh et al, 2019;AlKhalil et al, 2020;Hamdan et al, 2020 ;Kasabri et al, 2020;Al-Nuaimi et al, 2021 ;Shakoor et al, 2021;Haj Hussein et al, 2022;Hallaq et al, 2022;Khaleel et al, 2022;Qashou et al, 2022;Salih et al, 2022). The mechanism of reduction of cell viability was adopted so that Dose-response curves were plotted and values were expressed as percentage of control optical density and IC 50 values 50% inhibitory concentration were estimated by regression analysis (Piazzini et al, 2019).…”

“…Selectivity index (SI) is the term that describes the safety of tested drugs. It is calculated by dividing IC 50 value of tested compound on fibroblasts by the least IC 50 value of the same compound on any specific pathological cell line (Hoffmann, et al, 2011;Sweidan et al, 2017 ;Mamdooh et al, 2019;AlKhalil et al, 2020;Hamdan et al, 2020 ;Kasabri et al, 2020;Al-Nuaimi et al, 2021 ;Shakoor et al, 2021;Haj Hussein et al, 2022;Hallaq et al, 2022;Khaleel et al, 2022;Qashou et al, 2022;Salih et al, 2022).…”

Newly Substituted Anilino-Fluoroquinolones with Proliferation Inhibition Potential against a Panel of Cancer Cell Lines

“…Recently antilipolytic-Antiproliferative Activities of Novel AntidiabesityTriazolo/Fluoroquinolones were substantially signified for anti-inflammatory responses (Arabiyat et al, 2020) exceeding the sensitive and robust indomethacin in against LPS-induced nitric oxide production in studied cells. Essentially more optimally Functionalized FQs as a Potentially Novel Class of Anti-inflammatory and Anti-glycation Compounds were subjected to Pharmacological Appraisal (Hamdan et al, 2019;AlShahrabi et al, 2020). This kind of activity can suggestively be associated with the chelating properties possessed by the synthesized FQs (Hamdan et al, 2019).…”

“…Essentially more optimally Functionalized FQs as a Potentially Novel Class of Anti-inflammatory and Anti-glycation Compounds were subjected to Pharmacological Appraisal (Hamdan et al, 2019;AlShahrabi et al, 2020). This kind of activity can suggestively be associated with the chelating properties possessed by the synthesized FQs (Hamdan et al, 2019). Drug repurposing pharmacology of new safe therapeutic drugs has emerged as an alternative approach to overcome high toxicity and poor safety profile of clinical anticancer agents.…”

A Novel Class of Functionalized Synthetic Fluoroquinolones with Dual Antiproliferative - Antimicrobial Capacities

“…Target compounds (Arabiyat et al, 2016a,b;Alabsi et al, 2018;Jumah, 2018;AlShahrabi et al, 2020) were prepared as anti-pancreatic lipase and anticancer activities. Same compounds were rescreened and evaluated for their dual antiglycation-antiinflamation action (Hamdan et al, 2019;AL-AShahrabi et al, 2020)…”