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The higher prevalence of cancer and the unmet need for antioxidant/anti‐inflammatory chemotherapeutic compounds with little side effect are of utmost importance. In addition, the increased likelihood of failure in clinical trials along with increasing development costs may have diminished the range of choices among newer drugs for clinical use. This has dictated the necessity to seek out novel medications by repurposing as it needs less time, effort, and resources to explore new uses of a current or unsuccessful medication. In this study, we examined the biological activity of 10 potential quinoline derivatives. Given the half‐maximal inhibitory concentration (IC50 value) in lipopolysaccharide (LPS) induced inflammation of RAW264.7 mouse macrophages, all commercial FQs and selected quinolines (quinoline‐4‐carboxlic and quinoline‐3‐carboxylic acids) exerted impressively appreciable anti‐inflammation affinities versus classical NSAID indomethacin without related cytotoxicities in inflamed macrophages. Conversely, all 14 tested compounds lacked antioxidative DPPH radical scavenging capacities as compared to ascorbic acid. Gemifloxacin, considerably unlike markets FQs, indomethacin and quinoline derivatives, exerted exceptional and differential antiproliferation propensities in colorectum SW480, HCT116, and CACO2, pancreatic PANC1, prostate PC3, mammary T47D, lung A375, and melanoma A549 adherent monolayers using the sulforhodamine B colorimetric method versus antineoplastic cisplatin. All quinoline derivatives and gemifloxacin alike, but not levofloxacin, ciprofloxacin, or indomethacin, displayed substantially selective viability reduction affinities in prolonged tumor incubations of cervical HELA and mammary MCF7 cells. Specifically kynurenic acid (hydrate), quinoline‐2‐carboxylic acid, quinoline‐4‐carboxylic acid, quinoline‐3‐carboxylic acid, and 1,2‐dihydro‐2‐oxo‐4‐quinoline carboxylic acids possessed the most remarkable growth inhibition capacities against mammary MCF7 cell line, while quinoline‐2‐carboxylic acid was the only quinoline derivative with significant cytotoxicity on cervical HELA cancer cells. It is highly speculated that chelation with divalent metals via co‐planarity with close proximity of the COOH and the N atom could have the potential molecular mechanism for optimally promising repurposed pharmacologies. Conclusively, this study revealed the considerably profound repurposed duality of cytotoxicity and anti‐inflammation pharmacologies of quinoline derivatives. Activity‐guided structural modifications of the present nuclear scaffolds can be inherently linked to the betterment and enhancement of their repurposed pharmacologies. [ABSTRACT FROM AUTHOR]

Intense efforts by the pharmaceutical industry have been made to identify new targets for obesity diabetes (diabesity). Pancreatic triacylglycerol lipase (PL) inhibition is an interesting putative target for obesity management. Fluoroquinolones (FQs) have been identified as potent inhibitors of PL. The aim of this research was to synthesize novel FQs and evaluate their in vitro antilipolytic and antiproliferative properties. Characterization of the synthesized FQs was carried out with NMR, MS, IR, and EA. Like orlistat, potential FQs' modulation of PL was quantified colorimetrically (n = 3) and was further supported by docking studies. Compared with cisplatin, FQs' antiproliferative propensities against a panel of obesity related colorectal cancer cell lines were investigated with Sulforhodamine B assay. Twelve novel FQs (2A-5A, 2B-5B, and 2C-5C) were synthesized and characterized. The PL-I[C.sub.50] values of tested FQs were in the range of 6.8-165.7 [micro]mol/L. FQ 4A was the most active antiproliferative compound against HCT116 with an I[C.sub.50] value of 3.5 [micro]mol/L. Their selectivity of growth inhibition for safety examination using normal periodontal ligament fibroblasts (PDL) in comparison with cisplatin's lack of differential cytotoxicity was reported. Lipophilicity and hydrogen bonding were found essential for both activities. Conclusively, FQs are robustly proven for their emerging in vitro anti-obesity and antiproliferative activities. Key words: fluoroquinolones, pancreatic lipase, colorectal cancer, orlistat, cisplatin. L'industrie pharmaceutique a deploye d'intenses efforts pour trouver de nouvelles cibles du diabète lie à l'obesite (diabesite). L'inhibition de la triacylglycerol lipase pancreatique (PL) est une cible presumee interessante pour la prise en charge de l'obesite. Les fluoroquinolones (FQ) ont ete reconnues comme de puissants inhibiteurs de la PL. L'objectif des presents travaux etait de synthetiser de nouvelles FQ et d'evaluer leurs proprietes antilipolytiques et antiproliferatives in vitro. Nous avons caracterise les FQ que nous avons synthetisees par resonance magnetique nucleaire, spectrometrie de masse, spectroscopie infrarouge et analyse elementaire. Avec l'orlistat comme reference, la modulation potentielle de la PL par les FQa ete quantifiee par colorimetrie (n = 3) et corroboree par des etudes de modelisation. À l'aide du test à la sulforhodamine B, nous avons compare l'activite antiproliferative des FQ contre une serie de lignees cellulaires de cancer colorectal lie à l'obesite à celle du cisplatine. Nous avons synthetise et caracterise douze nouvelles FQ(2A-5A, 2B-5B et 2C-5C). Les valeurs de la CI50 des FQevaluees à l'egard de la PL variaient entre 6,8 et 165,7 [micro]M. La FQ 4A etait le compose possedant la plus grande activite antiproliferative contre les cellules HCT116, sa CI50 etant de 3,5 [micro]M. En evaluant l'innocuite de ces composes en presence de fibroblastes du ligament parodontal (PDL) normaux, nous avons observe qu'ils presentaient une meilleure selectivite sur le plan de l'inhibition de la croissance cellulaire que le cisplatine, lequel est caracterise une cytotoxicite peu selective. Nous avons constate que leur caractère lipophile et la presence de liaisons hydrogène etaient des facteurs essentiels à leur activite dans les deux types d'essais. En conclusion, les FQ sont des composes très prometteurs dont l'activite anti-obesite et antiproliferative a ete demontree in vitro. [Traduit par la Redaction] Mots-cles : fluoroquinolones, lipase pancreatique, cancer colorectal, orlistat, cisplatine., Introduction Intense efforts by the pharmaceutical industry have been made to identify new targets for obesity diabetes (diabesity). Although the prevalence of obesity is increasing at an alarming rate, only [...]

Background The extensive clinical use of Fluoroquinolones (FQs) led to the development of bacterial resistance against these agents. In this work, new lipophilic FQs were designed, prepared and screened against standard and resistant bacteria. A series of novel 7-substituted anilino-8-nitroFQ acids 3 (a-e), their reduced derivatives 4 (a-e) and their triazolo 5 (a-c) were successfully prepared, identified and characterized using NMR, and MS. FQs 3-5(a-e) were then evaluated for the in vitro antibacterial activity against standard and resistant gram-positive and gram-negative strains using serial dilution method. Combination between the new FQs and different classes of antibiotics were also tested for possible synergistic effect using checkerboard technique. Results The outcomes of the new FQs showed comparable and superior activity against both the standard strains S.aureus and E.coli with remarkable activity against the standard S.aureus strain. The reduced series 4 were the most active group among all derivatives with nanogram concentrations for 4d (60 ng/mL) and 4e (15 ng/mL) against the standard gram positive strain. Our compounds revealed appreciable or comparable MIC mean values to standard against resistant gram-positive strains (MRSA) with no inhibitory activity against gram-negative strains (MDR E.coli). The hydroxyl derivatives 6 have showed the strongest MIC mean values among all compounds. Combination of these compounds with bacitracin, ampicillin and cephalexin showed synergistic effect with fractional inhibitory concentration (FIC) index between 0.185-0.375. While combinations with erythromycin, neomycin and tetracycline showed indifference effect with FIC index 2. Conclusions Evidently increasing number of hydrogen bond acceptor/donor leads to significant increase in activity presented by compounds 4e and 6e. These findings would open the floor for these novel antibacterial agents to be used alone or in combinations with conventional antibiotics for treatment of pathogenic bacteria. [ABSTRACT FROM AUTHOR]

Twenty-five structurally diverse compounds have been tested in vitro for their pancreatic lipase (PL) inhibitory activity. Despite the diversity of tested compounds, the relationship comprising structural attributes of the compounds could be established to correlate with the observed inhibitory activity. Compounds that exerted inhibitory action through surface activity were of different profile from the rest of compounds. When co-incubated with orlistat (OsT), important synergistic effects for some compounds (orphenadrine, gliclazide, cefuroxime and sulfacetamide) were revealed, while antagonistic effects were demonstrated for others (camphor sulfonic acid and dinitro salicylic acid). Docking studies for the most active molecules were performed and molecular interaction forces with the PL active site were identified. The results suggested co-binding of OsT along with the other inhibitor in the binding site in cases of synergistic effect but not in the case of antagonistic effect. These results were additionally supported by affinity capillary electrophoresis. In conclusion, synergistic lipase inhibitory activity between OsT and some other pharmaceutical compounds was demonstrated for the first time, which might help improve the pharmacological effect of OsT.