Comparative evaluation of fifteen anti-sickling agents.
Fifteen compounds reported to be inhibitors of gelation or sickling were studied by standard methods. These tests included (1) the determination of the solubility of deoxyhemoglobin S or Csat, (2) evaluation of sickling in whole SS blood at various pO2s, (3) measurement of the oxygen affinity of hemoglobin and blood, and (4) examination of red cell indices and morphology. Among the 4 noncovalent agents tested, butylurea was the most potent inhibitor of gelation and sickling in vitro; however, relatively high concentrations were required compared to the covalent agents. In the latter group, bis-(3,5 dibromosalicyl)-fumarate, nitrogen mustard, and dimethyladipimidate were especially effective inhibitors of gelation and/or sickling. All of these compounds require further development before they can be considered for clinical use.
D000755:Anemia, Sickle Cell / Q000188:drug therapy* / Q000378:metabolism; D000986:Antisickling Agents / Q000627:therapeutic use*; D001241:Aspirin / Q000031:analogs & derivatives / Q000627:therapeutic use; D001381:Azepines / Q000627:therapeutic use; D002221:Carbamyl Phosphate / Q000627:therapeutic use; D003485:Cyanates / Q000627:therapeutic use; D003538:Cystamine / Q000627:therapeutic use; D004119:Dimethyl Adipimidate / Q000627:therapeutic use; D004341:Drug Evaluation; D004909:Erythrocyte Indices; D005985:Glyceraldehyde / Q000627:therapeutic use; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007096:Imidoesters / Q000627:therapeutic use; D008466:Mechlorethamine / Q000627:therapeutic use; D010101:Oxygen Consumption; D010649:Phenylalanine / Q000627:therapeutic use; D011730:Pyridoxal / Q000627:therapeutic use; D012995:Solubility; D014508:Urea / Q000031:analogs & derivatives / Q000627:therapeutic use
D000986:Antisickling Agents; D001381:Azepines; D003485:Cyanates; D006454:Hemoglobins; D007096:Imidoesters; C035358:dibromoacetylsalicylic acid; C021630:bis(3,5-dibromosalicyl)fumarate; D004119:Dimethyl Adipimidate; D005985:Glyceraldehyde; D011730:Pyridoxal; D010649:Phenylalanine; D008466:Mechlorethamine; D002221:Carbamyl Phosphate; C006955:cetiedil; C021631:bis(3,5-dibromosalicyl)succinate; D014508:Urea; C100003:deoxyhemoglobin; C006865:butylurea; C010222:methyl acetimidate; C024835:potassium cyanate; D003538:Cystamine; D001241:Aspirin