Synthesis and biological evaluation of lisofylline (LSF) analogs as a potential treatment for Type 1 diabetes

Bioorganic and Medicinal Chemistry Letters

Volumn 16, Issue 13, 2006, Pages 3401-3405

  Cui, Peng ^a   Macdonald, Timothy L ^a   Chen, Meng ^b   Nadler, Jerry L ^b  

^a UNIVERSITY OF VIRGINIA   (United States)

^b UNIVERSITY OF VIRGINIA   (United States)

Author keywords

5 Aza 7 deazaxanthine; Lisofylline; LSF; LSF analogs; Type 1 diabetes

Indexed keywords

5 AZA 7 DEAZAXANTHINE; HETEROCYCLIC COMPOUND; LISOFYLLINE; NITROGEN; UNCLASSIFIED DRUG; XANTHINE DERIVATIVE;

ANIMAL CELL; APOPTOSIS; ARTICLE; CONTROLLED STUDY; DRUG SCREENING; DRUG SYNTHESIS; INSULIN DEPENDENT DIABETES MELLITUS; INSULIN RELEASE; MOUSE; NONHUMAN; PANCREAS ISLET BETA CELL;

ANIMALS; APOPTOSIS; CELL LINE; CHEMOPREVENTION; CYTOKINES; DIABETES MELLITUS, TYPE 1; DRUG EVALUATION, PRECLINICAL; HYPOGLYCEMIC AGENTS; INSULIN; INSULIN-SECRETING CELLS; MICE; MOLECULAR STRUCTURE; PENTOXIFYLLINE; STEREOISOMERISM;

EID: 33646844079     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2006.04.036     Document Type: Article

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15. 2. Culture vessels were coated with poly-d-lysine and gelatin (Sigma, St. Louis, MO) to retain detached and dead cells so that seeding cell numbers reflect the actual cell numbers after all treatment conditions. INS-1 cells were treated with the combination of recombinant mouse IL-1β (5 ng/ml), IFNγ (100 ng/ml), and TNFα (10 ng/ml; R&D Systems, Inc., Minneapolis, MN) suspended in complete RPMI medium. LSF (provided by Cell Therapeutics, Inc., Seattle, WA) and analogs were added simultaneously with the cytokines in complete RPMI medium. All treatments were performed for 18 h.
16. Beta cells were treated with apoptosis detecting dye for 2-3 h at room temperature. Apoptotic cells were recognized with purple-red color under a microscope. After washing to eliminate free dye and adding dye release reagent, color density was quantified by reading at OD 450 nM.
17. 2, 10 mm HEPES, and 0.1% BSA at 37 °C, pH 7.4. They were preincubated in the same buffer for 30 min, followed by 60-min incubation in KRB supplemented with 15 mM d-glucose (J. T. Baker, Phillipsburg, NJ). The supernatant was harvested and subjected to centrifugation to eliminate residue cells. Insulin secreted into the supernatant was measured by RIA with mouse insulin as a standard.