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.

Synthesis, in vivo and in silico analgesic and anti-inflammatory studies of α-D-ribofuranose derivatives.

Five α-D-ribofuranose analogues (2, 3, 4, 5 and 6) were synthesized in good yields from 3-O-benzyl-4-C-(hydroxymethyl)-1, 2-O-isopropylidene-α-D-ribofuranose (1). The synthesized compounds were then subjected to analgesic, anti-inflammatory, antimicrobial and antioxidant assays. Compound 3 demonstrated 79.74% (P < 0.001) writhing inhibition and highest reaction time of 2.55 ± 0.13 min (P < 0.001) after 30 min of oral administration in peripheral and central analgesic assay, respectively, at 50 mg/kg dose. Compound 2 and 6 exhibited significant anti-inflammatory activity at 100 mg/kg dose with paw edema inhibition of 91.15% (P < 0.001) and 95.13% (P < 0.001), respectively, in 4th hour. The synthesized analogues did not show notable antioxidant and antibacterial properties. Molecular docking study revealed higher binding affinity of -8.1 kcal/mol and -8.9 kcal/mol of compound 3 towards cyclooxygenase-1 and phospholipase A2, respectively, compared to -7.7 and -7.6 kcal/mol respectively for corresponding native ligands. Compound 2 demonstrated binding affinity of -9.1 kcal/mol towards interleukin-1 receptor-associated kinase-4 compared to -8.7 kcal/mol of the native ligand. The molecular properties related to drug likeness of compounds were found to be within acceptable range. Synthesized D-ribofuranose analogues demonstrated promising analgesic and anti-inflammatory activities and further development may lead to new potent analgesic and anti-inflammatory agents.

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.

Metformin Hydrochloride Loaded Mucoadhesive Microspheres and Nanoparticles for Anti-Hyperglycemic and Anticancer Effects Using Factorial Experimental Design.

Background: Metformin hydrochloride (HCl) microspheres and nanoparticles were formulated to enhance bioavailability and minimize side effects through sustained action and optimized drug-release characteristics. Initially, the same formulation design with different ratios of metformin HCl and Eudragit RSPO was used to formulate four batches of microspheres and nanoparticles using solvent evaporation and nanoprecipitation methods, respectively. Methods: The produced formulations were evaluated based on particle size and shape (particle size distribution (PSD), scanning electron microscope (SEM)), incompatibility (differential scanning calorimetry (DSC), Fourier-transform infrared (FTIR)), drug release pattern, permeation behavior, in vivo hypoglycemic effects, and in vitro anticancer potential. Results: Compatibility studies concluded that there was minimal interaction between metformin HCl and the polymer, whereas SEM images revealed smoother, more spherical nanoparticles than microspheres. Drug release from the formulations was primarily controlled by the non-Fickian diffusion process, except for A1 and A4 by Fickian, and B3 by Super case II. Korsmeyer-Peppas was the best-fit model for the maximum formulations. The best formulations of microspheres and nanoparticles, based on greater drug release, drug entrapment, and compatibility characteristics, were attributed to the study of drug permeation by non-everted intestinal sacs, in vivo anti-hyperglycemic activity, and in vitro anticancer activity. Conclusion: This study suggests that the proposed metformin HCl formulation can dramatically reduce hyperglycemic conditions and may also have anticancer potential.

Upsurge of Dengue Prevalence During the Third Wave of COVID-19 Pandemic in Bangladesh: Pouring Gasoline to Fire.

Recently, there has been an alarming increase in Coronavirus Disease-2019 (COVID-19) and dengue virus infection cases in Bangladesh. As the 2 viral diseases share many similar symptoms, healthcare practitioners are facing difficulty in correctly diagnosing them. Even with the help of confirmatory diagnostic tests, the misdiagnosis has been reported in several countries and cases of co-infections are also emerging. This study presents the clinical symptoms of dengue fever and COVID-19 and identifies the overlapping symptoms seen in these 2 diseases that might cause difficulty in diagnosis. We have also discussed cases of misdiagnosis and incidences of co-infection seen in other countries. Finally, we present our recommendations for preventing the surge of dengue and possible solutions for differentiating and managing these 2 diseases. Immediate measures are required from health practitioners and public health policymakers before these viral diseases spiral out of control.

A cross-sectional study of COVID-19-related knowledge, risk perceptions, and preventive practices among pharmacy students in Bangladesh.

OBJECTIVES: The coronavirus disease 2019 pandemic is a threat to public health that impacts the life of frontline pharmacists as they are more susceptible to getting infected by the coronavirus. This study aimed to assess the knowledge, risk perceptions, and preventive practices associated with coronavirus disease 2019 among pharmacy students of Bangladesh to evaluate their preparedness as future frontline workers against the ongoing pandemic. METHODS: An online-based cross-sectional study was conducted among pharmacy undergraduate students of Bangladesh during the early months of the pandemic in April 2020. Respondents voluntarily submitted an online questionnaire regarding sociodemographics, knowledge, risk perceptions, and preventive practices related to coronavirus disease 2019. RESULTS: A total of 418 participants submitted their responses, and we included 395 responses for final analysis. The mean age of the participants was 20.65 years. The study revealed that out of 395 pharmacy students, 68 (17.2%) had high levels of knowledge, 210 (53.2%) possessed high risk perceptions regarding coronavirus disease 2019, and 165 (41.7%) were adopting high levels of preventive practices. Average scores for knowledge, risk perceptions, and preventive practices were 5.7, 8.4, and 8.2 out of 10. Chi-square test and logistic regression analyses showed that having high knowledge levels was associated with high risk perceptions regarding coronavirus disease 2019. Similarly, higher risk perceptions were associated with having high knowledge and preventive measures, while higher preventive measures were associated with female gender, low monthly family income, and having high risk perceptions. CONCLUSION: We found moderate knowledge, risk perceptions, and preventive practices related to coronavirus disease 2019 among the undergraduate pharmacy students. We recommend awareness-building discussions or seminars focusing on pharmacy students. In addition, the upgradation of the existing curriculum may help future pharmacists.

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.

Medication understanding and health literacy among patients with multiple chronic conditions: A study conducted in Bangladesh.

Objectives: Medication understanding is critical for patients who suffer from multiple chronic conditions in order to reduce medication error and is often associated with poor health outcomes and low adherence. This study aims to identify the gap of medication knowledge among multiple chronic condition patients in Bangladesh, in order to aid physicians and other healthcare providers in improving health literacy. Methods: Individual interviews of a convenience sample of multiple chronic condition patients in Bangladesh were held where they were asked a number of questions for assessing medication related literacy. Results: More than 26% patients failed to cite the brand name of all their prescribed medications while the rate of patients not knowing the generic names was far worse (88.1%). Nearly 1 out of every 4 patients did not know the purpose of all their medications and more than half of the participants (55%) did not know the strengths of their drugs. While knowledge about medication routes and regimen was satisfactory, awareness regarding risk factors of medicine was lowest of all. Only 1 out of every 4 patients had a habit of reading drug information leaflet. Patient's ability to correctly state the purpose of their medication seemed to be positively associated with age (p=0.004) and negatively associated with number of medicines taken (p=0.03). Conclusions: Many patients demonstrated poor health literacy regarding medication. Routine review of medications from physician or health provider can significantly improve their health literacy, leading to better treatment outcome and medication adherence.

Synthesis and evaluation of pharmacological activities of some 3-O-benzyl-4-C-(hydroxymethyl)-1,2-O-isopropylidene-α-D-ribofuranose derivatives as potential anti-inflammatory agents and analgesics.

BACKGROUND AND PURPOSE: α-D-ribofuranose analogues are reported to have multifarious biological properties such as analgesic, anti-inflammatory, and antiviral activities. The present study aims to synthesize some α-D- ribofuranose derivatives and investigate their biological properties. EXPERIMENTAL APPROACH: Four derivatives (2a, 2b, 3, and 4) were synthesized from the starting material 3-O- benzyl-4-C-(hydroxymethyl)-1,2-O-isopropylidene-α-D-ribofuranose via subsequent benzylation, tosylation, and acetylation reactions in good yields. The compounds were confirmed by spectroscopic methods such as Fourier-transform infrared (FTIR) and proton nuclear magnetic resonance (1HNMR), and then evaluated for various pharmacological activities using standard in vitro and in vivo procedures. FINDINGS / RESULTS: Compound 2a (50 mg/kg) exhibited both central and peripheral analgesic activity in the tail immersion test (2.52 ± 0.14 min tail flicking reaction time after 30 min from administration, P < 0.001) and the acetic acid-induced writhing test (65.33 ± 2.06% reduction in abdominal writhing, P < 0.001) respectively. In the anti-inflammatory assay, percent paw edema inhibition of carrageenan-induced rats for compounds 2a and 4 (100 mg/kg) after 4 h of administration were 82.6% (P < 0.001) and 87.6% (P < 0.001), respectively. The compounds were also tested for antioxidant activity in 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay, antimicrobial property in disk diffusion assay, and cytotoxicity in HeLa cell line; however, no significant results were observed in any of those tests. CONCLUSION AND IMPLICATIONS: Our study indicated that some of the synthesized compounds exhibited promising analgesic and anti-inflammatory effects and may serve as potential lead compounds.