Influence of chalcone analogues on serum glucose levels in hyperglycemic rats.
A series of chalcone derivatives from 3,4-methylenedioxybenzaldehyde and substituted acetophenones have been synthesized and investigated as antihyperglycemic agents in a glucose loaded animal model. Chalcones with biological activity were compared with lispro, regular insulin and tolbutamide effects on serum glucose levels. Compound 01, without substituent in the A-ring was not able to change glycemic levels. On the other hand, compounds 03, 04, 05, 09 and 10 with substitutions at position 3' and/or 4' in the A-ring caused significant reduction in serum glucose levels. Concerning the antihyperglycemic effect, compounds 03 and 05 (methoxy substituent) inhibited the hyperglycemia induced by glucose around 96% similar to that demonstrated for lispro insulin and tolbutamide at 60 min. A rapid and lasting antihyperglycemic effect was found with compound 09 and 10 (nitro substituent). In conclusion, besides the nature of the functional groups electron-donor substituent, as methoxy and hydroxyl or electron-acceptor, as nitro groups, the position of the group may be mandatory for biological activity.
Alberton
Elga Heloísa
EH
Universidade Federal de Santa Catarina, Departamento de Bioquímica, Centro de Ciências Biológicas, Campus Universitário, Bairro Trindade, Florianópolis, SC, Brazil.
Damazio
Rosangela Guollo
RG
Cazarolli
Luisa Helena
LH
Chiaradia
Louise Domeneghini
LD
Leal
Paulo César
PC
Nunes
Ricardo José
RJ
Yunes
Rosendo Augusto
RA
Silva
Fátima Regina Mena Barreto
FR
D000284:Administration, Oral; D000818:Animals; D001786:Blood Glucose / Q000032:analysis / Q000187:drug effects*; D002599:Chalcone / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005947:Glucose / Q000008:administration & dosage; D006943:Hyperglycemia / Q000097:blood / Q000188:drug therapy*; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000737:chemistry; D007328:Insulin / Q000008:administration & dosage; D008297:Male; D015394:Molecular Structure; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism; D013997:Time Factors; D014044:Tolbutamide / Q000008:administration & dosage
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D002599:Chalcone; D014044:Tolbutamide; D005947:Glucose