Synthesis of Sugar and Nucleoside Analogs and Evaluation of Their Anticancer and Analgesic Potentials.

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.

Knowledge, attitude and practices towards SARS-CoV-2 genetic mutations and emerging variants among the population in Bangladesh: a cross-sectional study.

OBJECTIVES: The coronavirus is continuously mutating and creating new SARS-CoV-2 variants. Public awareness about SARS-CoV-2 mutation is essential for effective preventive measures. The present study aimed to assess the knowledge, attitude and practices (KAP) towards SARS-CoV-2 variants among the general population in Bangladesh. DESIGN: We conducted this online survey between 9 April 2021 and 10 May 2021 using structured questionnaires to collect the information. SETTING: We distributed the survey link among the participants from all 64 districts of Bangladesh using social media platforms. PARTICIPANTS: A total of 1,090 respondents completed this survey. After careful evaluation, we excluded 18 responses due to partial or incomplete information, and 1,072 responses entered into the final analysis. PRIMARY OUTCOME: The KAP of participants towards SARS-CoV-2 variants depends on their demographic backgrounds. Associations between demographic characteristics and the likelihood of having adequate KAP were estimated using adjusted logistic regressions. RESULTS: Among the participants, 42% had a poor knowledge level, 4% had a low attitude level and 14% had a poor practice score. The average knowledge, attitude and practice score were 2.65, 4.194 and 4.464 on a scale of 5, respectively. Only 51.8% of the participants knew about mutant strains, and only 47.6% knew about the effectiveness of vaccines against new variants. The key factors associated with poor knowledge levels were educational levels, area of residence, geographic location, and concern regarding COVID-19. Sociodemographic factors for poor attitude levels were geographic location, vaccination and concern regarding COVID-19. The pivotal factors in determining poor practice scores were the residence area of people and concern regarding COVID-19. CONCLUSIONS: The knowledge level and positive attitude are associated with better preventive measures against SARS-CoV-2 variants. Based on these findings, we recommended several awareness programmes on SARS-CoV-2 mutations and variants for the rural population in Bangladesh to increase overall awareness levels.

Antimicrobial Diterpenes: Recent Development From Natural Sources.

Antimicrobial resistance has been posing an alarming threat to the treatment of infectious diseases over the years. Ineffectiveness of the currently available synthetic and semisynthetic antibiotics has led the researchers to discover new molecules with potent antimicrobial activities. To overcome the emerging antimicrobial resistance, new antimicrobial compounds from natural sources might be appropriate. Secondary metabolites from natural sources could be prospective candidates in the development of new antimicrobial agents with high efficacy and less side effects. Among the natural secondary metabolites, diterpenoids are of crucial importance because of their broad spectrum of antimicrobial activity, which has put it in the center of research interest in recent years. The present work is aimed at reviewing recent literature regarding different classes of natural diterpenes and diterpenoids with significant antibacterial, antifungal, antiviral, and antiprotozoal activities along with their reported structure-activity relationships. This review has been carried out with a focus on relevant literature published in the last 5 years following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A total of 229 diterpenoids from various sources like plants, marine species, and fungi are summarized in this systematic review, including their chemical structures, classification, and significant antimicrobial activities together with their reported mechanism of action and structure-activity relationships. The outcomes herein would provide researchers with new insights to find new credible leads and to work on their synthetic and semisynthetic derivatives to develop new antimicrobial agents.

Side Effects Following Administration of the First Dose of Oxford-AstraZeneca's Covishield Vaccine in Bangladesh: A Cross-Sectional Study.

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.