01946nas a2200361   4500000000100000008004100001653001200042653001400054653002200068653001200090653003000102653001400132653002800146653001000174653001600184100001600200700001800216700001600234700001500250700001100265700001500276700001300291700001600304700001700320700001400337700001300351700001800364245011300382300001400495490000700509520105400516022001401570       2014                            d10aleprosy10aAnalgesic10aAnti-inflammatory10aDapsone10aErythema Nodosum Leprosum10aM. leprae10aMolecular hybridization10aTNFα10aThalidomide1 aYamasaki PR1 aNascimento DC1 aChelucci RC1 aBelone AFF1 aRosa P1 aDiório SM1 aMelo TRF1 aBarbieri KP1 aPlaceres MCP1 aCarlos IZ1 aChung MC1 aDos Santos JL00aSynthesis and evaluation of novel dapsone-thalidomide hybrids for the treatment of type 2 leprosy reactions.  a3084-30870 v243 a<p>We synthesized a series of novel dapsone-thalidomide hybrids (3a-i) by molecular hybridization and evaluated their potential for the treatment of type 2 leprosy reactions. All of the compounds had analgesic properties. Compounds 3c and 3h were the most active antinociceptive compounds and reduced acetic acid-induced abdominal constrictions by 49.8% and 39.1%, respectively. The hybrid compounds also reduced tumor necrosis factor-α levels in lipopolysaccharide-stimulated L929 cells. Compound 3i was the most active compound; at concentrations of 15.62 and 125μM, compound 3i decreased tumor necrosis factor-α levels by 86.33% and 87.80%, respectively. In nude mice infected with Mycobacterium leprae in vivo, compound 3i did not reduce the number of bacilli compared with controls. Compound 3i did not have mutagenic effects in Salmonella typhimurium strains TA100 and TA102, with or without metabolic activation (S9 mixture). Our results indicate that compound 3i is a novel lead compound for the treatment of type 2 leprosy reactions.</p>  a1464-3405