Abstract
A new series of coumarin-linked imidazo[2,1-b][1,3,4]thiadiazoles were synthesized and evaluated for their cytotoxicity inhuman T-lymphocyte (CEM), human cervix carcinoma (HeLa) and murine leukemia cells (L1210). Among the tested compounds, 3-[5-bromo-2-(thiophen-2-ylmethyl)imidazo[2,1-b][1,3,4]thiadiazol-6-yl]-2Hchromen-2-one 9b exhibited cytotoxicity at 0.77 mu M against CEM, 1.6 mu M against L1210 and 0.38 mu M against HeLa cells. Compound 6-(2-oxo-2H-chromen-3-yl)-2-(thiophen-2-ylmethyl)imidazo[2,1-b][1,3,4]thiadiazol-5carbaldehyde 10b showed cytotoxicity at 3.5 mu M against CEM and at 9.5 mu M against HeLa cells. Further, molecular docking simulations performed to evaluate the possibility of these synthesized analogs as inhibitors of heat shock protein 90 (Hsp90), Pdb ID: 1UYL revealing that docking predictions are in good agreement with invitro results (-10.7 for 9b and -10.5 for 10b). The in-silico ADME parameters, pharmacokinetics and drug-likeness of all derivatives were examined in detail using the Swiss ADME webserver. By applying molecular dynamics simulation experiments a better stability was observed of compounds 8b, 9a, 10b and 11b.
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Kapsamı
Uluslararası
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Type
Hakemli
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Index info
WOS.SCI
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Language
English
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Article Type
None
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Keywords
Coumarin Imidazo[2 b ][1 4]thiadiazole Cytotoxicity Hsp90 In-silico ADME Molecular docking Levamisole Melphalan