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Design, Synthesis, SAR and Molecular Modeling Studies of Novel Imidazo[2,1‐ b ][1,3,4]Thiadiazole Derivatives as Highly Potent Antimicrobial Agents
Author(s) -
Tahtaci Hakan,
Karacık Hatice,
Ece Abdulilah,
Er Mustafa,
Şeker Mine Gül
Publication year - 2018
Publication title -
molecular informatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.481
H-Index - 68
eISSN - 1868-1751
pISSN - 1868-1743
DOI - 10.1002/minf.201700083
Subject(s) - adme , bacillus subtilis , chemistry , antimicrobial , aryl , antibacterial activity , staphylococcus aureus , stereochemistry , ring (chemistry) , candida albicans , docking (animal) , structure–activity relationship , escherichia coli , quantitative structure–activity relationship , lead compound , molecular model , combinatorial chemistry , organic chemistry , bacteria , microbiology and biotechnology , biochemistry , alkyl , in vitro , biology , medicine , nursing , gene , genetics
In this study, a novel series of phenyl substituted imidazo[2,1‐ b ][1,3,4]thiadiazole derivatives were synthesized, characterized and explored for antibacterial activity against Gram‐negative Escherichia coli, Gram‐positive Staphylococcus aureus and Bacillus subtilis and antifungal activity against Candida albicans . Most of the synthesized compounds exhibited remarkable antimicrobial activities, some of which being ten times more potent than positive controls. The most promising compound showed excellent activity with MIC value of 0.03 μg/ml against both S. aureus and B. subtilis (MIC values of positive compound Chloramphenicol are 0.4 μg/ml and 0.85 μg/ml, respectively). Furthermore, structure‐activity relationship was also investigated with the help of computational tools. Some physicochemical and ADME properties of the compounds were calculated too. The combination of electronic structure calculations performed at PM6 level and molecular docking simulations using Glide extra‐precision mode showed that the hydrophobic nature of keto aryl ring with no electron withdrawing substituents at para position enhances activity while electron‐donating substituents at the second aryl ring is detrimental to activity.