ABSTRACT
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 IC50 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.
Subject(s)
Antineoplastic Agents , Nucleosides , Analgesics/chemistry , Animals , Antineoplastic Agents/chemistry , Cyclooxygenase 2/metabolism , Dose-Response Relationship, Drug , HeLa Cells , Humans , Mice , Molecular Docking Simulation , Molecular Structure , Nucleosides/pharmacology , Structure-Activity Relationship , SugarsABSTRACT
In response to the raging COVID-19 pandemic, Bangladesh started its vaccine administration in early 2021; however, due to the rapid development and launch of the vaccines in the market, many people had concerns regarding the safety of these vaccines. The purpose of this study was to evaluate the side effects that were experienced by the Bangladeshi residents after receiving the first dose of the Oxford-AstraZeneca's Covishield vaccine (ChAdOx1nCoV-19). The study was conducted using both online and printed questionnaires and the data were analysed using SPSS. The results included the responses of 474 vaccine recipients from March-April 2021. Pain at the site of injection, fever, myalgia, fatigue and headache were the most commonly reported symptoms, and the overall side effects were found to be significantly more prevalent in the younger population (p ≤ 0.05). These findings were consistent with the results indicated by the clinical trial of ChAdOx1nCoV-19. Logistic regression analysis further revealed that compared to people aged 70 years or above, the incidence of reported side effects was significantly higher in people aged 18-30 years (odds ratio (OR) = 8.56), 31-40 years, (OR = 5.05), 41-50 years (OR = 4.08), 51-60 years (OR = 3.77) and 61-70 years (OR = 3.67). In addition, a significantly higher percentage of female participants suffered from post-vaccination side effects compared to males (OR = 1.51). It was concluded that the Covishield vaccine was well-tolerated among people of different age groups. Nevertheless, further long-term follow-up study with a larger sample size is warranted to establish the long-term safety of the COVID-19 vaccine.