New Thiazolidine-4-One Derivatives as SARS-CoV-2 Main Protease Inhibitors

It has been more than four years since the first report of SARS-CoV-2, and humankind has experienced a pandemic with an unprecedented impact. Moreover, the new variants have made the situation even worse. Among viral enzymes, the SARS-CoV-2 main protease (Mpro) has been deemed a promising drug target vs. COVID-19. Indeed, Mpro is a pivotal enzyme for viral replication, and it is highly conserved within coronaviruses. It showed a high extent of conservation of the protease residues essential to the enzymatic activity, emphasizing its potential as a drug target to develop wide-spectrum antiviral agents effective not only vs. SARS-CoV-2 variants but also against other coronaviruses. Even though the FDA-approved drug nirmatrelvir, a Mpro inhibitor, has boosted the antiviral therapy for the treatment of COVID-19, the drug shows several drawbacks that hinder its clinical application. Herein, we report the synthesis of new thiazolidine-4-one derivatives endowed with inhibitory potencies in the micromolar range against SARS-CoV-2 Mpro. In silico studies shed light on the key structural requirements responsible for binding to highly conserved enzymatic residues, showing that the thiazolidinone core acts as a mimetic of the Gln amino acid of the natural substrate and the central role of the nitro-substituted aromatic portion in establishing π-π stacking interactions with the catalytic His-41 residue

Antimicrobial and Anticancer Activities of Some Partially Acylated Thymidine Derivatives

The principal cause of human deaths in the world is primarily due to harmful pathogenic microbes as bacteria, a virus, and fungi. Searching for antimicrobial agents to prevent deaths with new structures and modes of action is an essential strategy of the research. Therefore, in the present study has been undertaken of thymidine and of its eleven acylated derivatives were employed as test chemicals for in vitro antibacterial evaluation against five human pathogenic bacteria. The compounds were also screened for antifungal functionality tests against two phytopathogenic fungi. It was observed that a good number of tested compounds exhibited moderate to good antimicrobial activities. It was also observed that these acylated compounds were more effective against the phytopathogenic fungi than those of the bacterial strains. Encouragingly, several tested chemicals showed better antibacterial and antifungal activities than the standard antibiotics employed. The minimum inhibition concentration (MIC) values of the compounds 3 (5´-O-butyrylthymidine), 7 (5´-O-palmitoylthymidine) and 12 (5´-O-4- dichloroacetylthymidine) were found to be 0.32 mg/ml and minimum bactericidal concentrations (MBC) values were found to be 0.63 mg /ml in each case. On the other hand, the minimum fungal concentration (MFC) was found to be (1.25 mg/ml) in the case of compound 7 (i.e., palmitoyl derivative) which may be used as antifungal active drug providing further investigation. In vitro MTT assays revealed that compounds 4 (5´-O-hexanoylthymidine) and 7 (5´-O-palmitoylthymidine) were effective against Ehrlich’s ascites carcinoma (EAC) cells and IC50 values were found to be 920.88 μg/ml and 792.90 μg/ml, respectively. So these compounds may be targeted for future studies for their usage as broad-spectrum antibiotics. J. Bio-Sci. 29(1): 11-22, 2021 (June)</jats:p

Prevalence of asymptomatic bacteriuria in pregnant women

Introduction: Women with asymptomatic bacteriuria during pregnancy are more likely to deliver premature or low birth weight babies and having a 20 – 40 percent increased risk of developing pyelonephritis during pregnancy compared with women without bacteriuria. Asymptomatic bacteriuria is a microbiological diagnosis based on urine culture from persons without signs or symptoms of urinary tract infection. Objectives: The aim of this study was to determine the prevalence of asymptomatic bacteriuria in pregnant women and also to determine the relationship between the asymptomatic bacteriuria and pyuria to isolate the causative pathogens and to find out the antimicrobial susceptibility pattern of the isolates. Methods: A total of 540 urine specimen were collected from 540 asymptomatic pregnant women for urinary tract infection, over a period 2 years from January 2011 to December 2012 at Border Guard Bangladesh (BGB) Hospital, Pilkhana, Dhaka. All specimens were processed using standard microbiological procedures. All the subjects were evaluated for bacteriuria. Results: The prevalence of asymptomatic bacteriuria was 10.2% . Pyuria was found in 15.9% of cases. Escherichia coli (80%) was the commonest causative agent of asymptomatic bacteriuria followed by Staphylococcus saprophyticus (14.5%) and Pseudomonas spp.(5.5%). Nitrofurantoin was found to be highly sensitive to most of the isolates. 64 JAFMC Bangladesh. Vol 9, No 2 (December) 2013 Conclusion: Screening for bacteriuria in pregnancy and proper treatment of diagnosed cases must be considered as an essential part of antenatal care in our country. To prevent complications of asymptomatic bacteriuria, all pregnant women should be screened at the first antenatal visit. A negative test for pyuria is not a reliable indicator of the absence of asymptomatic bacteriuria in pregnant women. DOI: http://dx.doi.org/10.3329/jafmc.v9i2.21830 Journal of Armed Forces Medical College Bangladesh Vol.9(2) 2013</jats:p