Synthesis of Sugar and Nucleoside Analogs and Evaluation of Their Anticancer and Analgesic Potentials.
Fahad HussainFahad Imtiaz RahmanPoushali SahaAtsushi MikamiTakashi OsawaSatoshi ObikaS M Abdur RahmanPublished in: Molecules (Basel, Switzerland) (2022)
Chemical modification of sugars and nucleosides has a long history of producing compounds with improved selectivity and efficacy. In this study, several modified sugars ( 2 - 3 ) and ribonucleoside analogs ( 4 - 8 ) have been synthesized from α-d-glucose in a total of 21 steps. The compounds were tested for peripheral anti-nociceptive characteristics in the acetic acid-induced writhing assay in mice, where compounds 2 , 7 , and 8 showed a significant reduction in the number of writhes by 56%, 62%, and 63%, respectively. The compounds were also tested for their cytotoxic potential against human HeLa cell line via trypan blue dye exclusion test followed by cell counting kit-8 (CCK-8) assay. Compound 6 demonstrated significant cytotoxic activity with an IC 50 value of 54 µg/mL. Molecular docking simulations revealed that compounds 2 , 7 , and 8 had a comparable binding affinity to cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzymes. Additionally, the bridged nucleoside analogs 7 and 8 potently inhibited adenosine kinase enzyme as well, which indicates an alternate mechanistic pathway behind their anti-nociceptive action. Cytotoxic compound 6 demonstrated strong docking with cancer drug targets human cytidine deaminase, proto-oncogene tyrosine-protein kinase Src, human thymidine kinase 1, human thymidylate synthase, and human adenosine deaminase 2. This is the first ever reporting of the synthesis and analgesic property of compound 8 and the cytotoxic potential of compound 6 .
Keyphrases
- molecular docking
- endothelial cells
- protein kinase
- induced pluripotent stem cells
- pluripotent stem cells
- neuropathic pain
- tyrosine kinase
- squamous cell carcinoma
- molecular dynamics
- emergency department
- stem cells
- adipose tissue
- blood pressure
- high throughput
- insulin resistance
- mesenchymal stem cells
- cell proliferation
- type diabetes
- small molecule
- mass spectrometry
- transcription factor
- risk assessment
- adverse drug
- electronic health record
- aqueous solution