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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 [...]

OBJECTIVE. This study was a comparison of topical ciprofloxacin/dexamethasone otic suspension to oral amoxicillin/clavulanic acid suspension in children with acute otitis media with otorrhea through tympanostomy tubes. METHODS. This was a randomized, observer-masked, parallel-group, multicenter trial of topical ciprofloxacin/ dexamethasone otic suspension versus amoxicillin/clavulanic acid suspension in 80 children aged 6 months to 12 years with acute otitis media with otorrhea through tympanostomy tubes of [less than or equal to] 3 weeks' duration and visible otorrhea. Patients were randomly assigned to receive either 4 drops of topical ciprofloxacin 0.3%/dexamethasone 0.1% (Ciprodex Sterile Otic Suspension) into the affected ear(s) twice daily for 7 days or 600 mg of amoxicillin/42.9 mg of clavulanic acid oral suspension (Augmentin ES-600 Oral Suspension) every 12 hours for 10 days. Clinical signs and symptoms of acute otitis media with otorrhea through tympanostomy tubes were evaluated on days 1 (baseline), 3, 11 (end-of-therapy), and 18 (test-of-cure), and twice-daily assessments of otorrhea were recorded in patient diaries. RESULTS. The median time to cessation of otorrhea was significantly shorter with ciprofloxacin/dexamethasone otic suspension than with amoxicillin/clavulanic acid suspension (4.0 vs 7.0 days; n = 79). This resulted in significantly more clinical cures at the test-of-cure visit (85% vs 59%, respectively). Frequent adverse events (> 3 %) related to ciprofloxacin/dexamethasone otic suspension included ear pain (5.1%) and related to amoxicillin/clavulanic acid suspension included diarrhea (19.5%), dermatitis (7.3%), and gastroenteritis (4.9%). CONCLUSIONS. Topical otic treatment with ciprofloxacin/ dexamethasone otic suspension is superior to treatment with oral amoxicillin/clavulanic acid suspension and results in more clinical cures and earlier cessation of otorrhea with fewer adverse effects in children with acute otitis media with otorrhea through tympanostomy tubes. KEYWORDS. otitis media, tympanostomy tubes, ciprofloxacin, dexamethasone, oral antibiotics., Joseph Dohar, MD, William Giles, MD, Peter Roland, MD, Nadim Bikhazi, MD, Sean Carroll, DO, Roderick Moe, MD, Bradley Reese, MD, Sheryl Dupre, MS, Michael Wall PhD, David Stroman, PhD, [...]