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Design, synthesis, biological evaluation, and docking study of new acridine‐9‐carboxamide linked to 1,2,3‐triazole derivatives as antidiabetic agents targeting α‐glucosidase
Author(s) -
Asgari Mohammad S.,
Tahmasebi Behnam,
Mojtabavi Somayeh,
Faramarzi Mohammad A.,
Rahimi Rahmatollah,
Ranjbar Parviz R.,
Biglar Mahmood,
Larijani Bagher,
Rastegar Hossein,
MohammadiKhanaposhtani Maryam,
Mahdavi Mohammad
Publication year - 2020
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.4142
Subject(s) - chemistry , acarbose , acridine , carboxamide , docking (animal) , adme , stereochemistry , cytotoxicity , 1,2,3 triazole , in vitro , triazole , combinatorial chemistry , enzyme , biochemistry , organic chemistry , medicine , nursing
A new series of acridine‐9‐carboxamide‐1,2,3‐triazole derivatives 7a‐m were designed, synthesized, and evaluated as novel α‐glucosidase inhibitors. Acridine‐9‐carboxamide‐1,2,3‐triazole scaffold has been designed by combination of effective moieties from potent α‐glucosidase inhibitors. Most of the synthesized compounds were more potent than standard inhibitor acarbose. Among the title compounds, the most potent compounds were compounds 7j , 7k , and 7a with IC 50 values of 120.2 ± 1.0, 151.1 ± 1.4, and 157.6 ± 1.6 μM, respectively (IC 50 value of acarbose = 750.0 ± 10.0 μM). Docking study of the most potent compounds demonstrated that these compounds formed stable complexes with α‐glucosidase active site. Anti‐α‐amylase assay of compounds 7j , 7k , and 7a was performed and no activity was observed. in vitro cytotoxicity assay of the latter compounds revealed that these compounds were not cytotoxic toward human normal (HDF) and cancer (MCF‐7) cell lines. ADME and toxicity prediction of compounds 7j , 7k , and 7a were also performed.