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Thiourea Derivatives Based on the Dapsone‐Naphthoquinone Hybrid as Anticancer and Antimicrobial Agents: In Vitro Screening and Molecular Docking Studies
Author(s) -
Alimohammadi Aazam,
Mostafavi Hossein,
Mahdavi Majid
Publication year - 2020
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.201903179
Subject(s) - thiourea , chemistry , antimicrobial , staphylococcus epidermidis , antibacterial activity , naphthoquinone , microbiology and biotechnology , staphylococcus aureus , bacteria , biology , organic chemistry , genetics
According to the structure‐activity relationships (SAR), we synthesized a series of novel thiourea derivatives based on the dapsone‐naphthoquinone hybrid by the nucleophilic addition reaction of various primary/secondary amines to 2‐[4‐(4‐isothiocyanato‐benzenesulfonyl)‐phenylamino]‐[1,4]naphthoquinone (4) . All thiourea derivatives (5 a‐j) were screened for in vitro anticancer activity against human leukemia cell line (K562). Thiourea derivative containing N ‐methyl piperazine ( 5 h) was identified as the most effective molecule with IC 50 = 5.8±0.55 μM. Antimicrobial activity of thiourea derivatives (5 a – j) was evaluated in vitro against six strains of bacteria ( Staphylococcus aureus , Staphylococcus epidermidis , Bacillus subtilis , Escherichia coli , Salmonella enterica and Klebsiella pneumoniae ) and a fungus Candida kefyr by the microdilution method. Interestingly, compound 5 h exhibited better antibacterial activity compared with the dapsone as a positive control against S. epidermidis. The molecular docking studies indicated that compound 5 h may act as anticancer agent through the inhibition of Abl kinase and T315I Abl mutant.