Synthesis, thymidine phosphorylase inhibition and molecular modeling studies of 1,3,4-oxadiazole-2-thione derivatives.
Thymidine phosphorylase (TP) inhibitors have attracted great attention due to their ability to suppress the tumors formation. In our ongoing research, a series of 1,3,4-oxadiazole-2-thione (1-12) has been synthesized under simple reaction conditions in good to excellent yields (86-98%) and their TP inhibition potential has also been evaluated. The majority of synthesized compounds showed moderate thymidine phosphorylase inhibitory activity with IC50 values ranging from 38.24±1.28 to 258.43±0.43μM, and 7-deazaxanthine (7DX) was used as a reference compound (IC50 38.68±4.42). The TP activity was very much dependent on the C-5 substituents; among this series the compound 6 bearing 4-hydroxyphenyl group was found to be the most active with IC50 38.24±1.28μM. Molecular docking studies revealed their binding mode.
Department of Chemistry, COMSATS Institute of Information Technology, Abbottabad 22060, Pakistan. Electronic address: sashahzad@ciit.net.pk.
Sohail Anjum
SA
Shahzad
Interdisciplinary Research Centre in Biomedical Materials, COMSATS Institute of Information Technology, Lahore 54000, Pakistan. Electronic address: drmyar@ciitlahore.edu.pk.
Muhammad
M
Yar
Department of Physicochemical Drug Analysis, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Cracow, Poland.
Marek
M
Bajda
Interdisciplinary Research Centre in Biomedical Materials, COMSATS Institute of Information Technology, Lahore 54000, Pakistan.
Lubna
L
Shahzadi
Department of Chemistry, Government College University, Faisalabad 38000, Pakistan.
Zulfiqar Ali
ZA
Khan
Department of Chemistry, Government College University, Faisalabad 38000, Pakistan.
Syed Ali Raza
SA
Naqvi
Department of Chemistry, GC University, Lahore 54000, Pakistan.
Sadaf
S
Mutahir
Department of Allied Health Sciences and Chemical Pathology, Department of Human Genetics and Molecular Biology, University of Health Sciences, Lahore, Pakistan.
Nasir
N
Mahmood
Hussain Ibrahim Jamal Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
Khalid Mohammed
KM
Khan
D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D020128:Inhibitory Concentration 50; D062105:Molecular Docking Simulation; D010069:Oxadiazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013871:Thiones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013939:Thymidine Phosphorylase / Q000037:antagonists & inhibitors* / Q000378:metabolism
D004791:Enzyme Inhibitors; D010069:Oxadiazoles; D013871:Thiones; C583463:1,3,4-oxadiazole; D013939:Thymidine Phosphorylase
Anti-cancer; Molecular modeling; Oxadiazole-2-thione; Thymidine phosphorylase