Nucleoside derivatives are important therapeutic drugs and are the focal point in the ongoing search for novel, more potent drug targets. In this study, a new series of pyrimidine nucleoside i.e., uridine (1) derivatives were synthesized via direct method and evaluated for their antimicrobial potential activity. The title compound uridine (1) was treated with triphenylmethyl chloride in pyridine to give the 5´-O-(triphenylmethyl)uridine derivative (2), which was subsequently derivatized to create a series of 2´,3´-di-O-acyl analogs containing a wide variety of functionalities in a single molecular framework. In vitro antimicrobial functionality tests were determined against both human and plant pathogens by disc diffusion and food poisoned techniques. The chemical structures of the synthesized compounds were confirmed on the basis of their spectral, analytical, physicochemical data. The antimicrobial results indicated that the synthesized derivatives exhibited moderate to good antibacterial and antifungal activity; in particular, they were found to be more effective against fungal phytopathogens than against human bacterial strains. Compounds 7, 9, and 14 were of particular interest as they exhibited noteworthy antifungal and antibacterial properties. In vitro MTT assays revealed that compound 9 was effective against Ehrlich’s ascites carcinoma (EAC) cells, resulting in 7.12% and 1.34% cell growth inhibition at concentrations of 200 and 6.25 µg/ml, respectively. The IC50 value for compound 9 was rather high and found to be 1956.25 µg/ml. Structure-activity relationship (SAR) studies were also conducted to predict structural and pharmacokinetic properties. The findings of this study indicate that the different uridine derivatives are potentially useful antimicrobial agents for the advancement of future pharmaceutical research.
In the present study fifteen Lactic Acid Bacteria (LAB) from milk and milk products were isolated, identified and tested for their antagonistic activity. All the samples were found to be acidic with a pH range of 6.0 to 6.8.The collected samples showed higher number of total bacterial load ranging from 3.24´10 5 to 1.04´10 8 cfu/ml. Out of fifteen isolates, nine isolates were found to belong to the genus Lactobacillus and identified as L. casei subsp. pseudoplantarum, L. homohiochii, L. salivarius, L. xylosus, L.fermentum, L.leichmannii , L.heterohiochii, L.casei, and L.plantarum,.The others were found to belong to the genus Streptococcus and identified as S. thermophilus , S. lactis, S. uberis, S.suis, S. faecalis, and S. equnius.The isolates showed antibacterial activity against four gram positive bacteria (Bacillus cereus, B. subtilis, B.megaterium, Staphylococcus aureus) and six gram negative bacteria (Escherichia coli, Shigella dysenteriae, Salmonella typhi, Salmonella paratyphi, Vibrio cholerae and Pseudomonas aeruginosa) by using the disc diffusion method. They also showed their antifungal activity against two fungi (Penicillium sp. and Aspergillus flavus) by modifying poisoned food technique. All of the fifteen isolates were active against one or more test pathogenic bacterial strains. Among them L. homohiochii (TM3/a) showed the highest zone of inhibition (30.3mm) against Salmonella typhi. Lactobacillus spp. showed more antifungal activity than Streptococcus spp. and Streptococcus uberis (TY4 /a) showed the highest antifungal activity (50%) against Penicillium sp.This preliminary work shows the potential application of LAB to improve safety of traditional fermented food and milk products.Bangladesh J Microbiol, Volume 29, Number 2, Dec 2012, pp 76-82
Poultry chickens are potential source of transmission of zoonotic Salmonella, into human food chain, causing food-borne illness and also hindering development of poultry industry in Bangladesh. The non-judicious uses of antibiotics in poultry farm have increased the multidrug resistant bacteria. So, this study reports the occurrence of Salmonella in poultry samples (meat, egg, liver and cloacal swab) and the antimicrobial resistance pattern of the isolates. This study was carried out throughout the period of May 2019-March 2020, at the bacteriological laboratory in the Department of Microbiology, University of Chittagong. Isolates were identified on the basis of cultural and biochemical tests from a total of 25 broiler samples (meat, liver, eggshell and cloacal swab). Antibiotic susceptibility pattern was observed using Kirby-Bauer disk diffusion method. The overall detection rate of Salmonella was 48% (12/25) and the highest occurrence was noticed in raw meat 62.5% and the lowest in liver (37.5%). The antimicrobial resistance tests revealed that all the isolates (n = 12) exhibited 100% resistance to vancomycin and cephalexin, followed by ampicillin (75%), nalidixic acid (58.33%), chloramphenicol (41.66%), doxycycline (50%), and neomycin (50%). On the other hand, ciprofloxacin showed 83.33%, ceftazidime and amoxicillin showed 91.6% sensitivity respectively. A considerably high proportion of isolates (11/12, 91.67%) was resistant to three or more antibiotics and 6 multidrug profiles were observed. The ampicillin-chloramphenicol-nalidixic acid-neomycin-cephalexindoxycycline-vancomycin (4/12) was more frequently observed phenotype in multidrug profiles. Finally, two multidrug-resistant strains of Salmonella
In recent, millions of people are living with the human immunodeficiency virus type 1 (HIV-1), which causes acquired immunodeficiency syndrome. HIV-1 reverse transcriptase (RT) is one of the main viral targets for HIV-1 inhibition. Pyrimidine nucleoside derivative, 3′-azido-3′-deoxythymidine (AZT) is a highly active nucleoside inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT). In this work, hydroxyl (-OH) groups of cytidine structure were modified with different aliphatic and aromatic groups to get 5´-O-acyl- and 2´,3´-di-O-acyl derivatives and then employed for molecular modeling, molecular docking, biological prediction, and pharmacological studies. Herein, we relate the optimization of cytidine and its acylated analogues applying density functional theory (DFT) with B3LYP/3-21G level theory to explore their thermochemical and molecular electrostatic potential (MEP) properties. Prediction of activity spectra for substances (PASS) indicated promising antiviral, anti-carcinogenic, and antifungal functionality of these cytidine esters compared to the antibacterial activities. To support this observation, their cytotoxic prediction and molecular docking studies have been performed against HIV-1 reverse transcriptase (RT) (PDB: 3V4I). Most of the molecules studied out here could bind near the crucial catalytic binding site, Tyr181, Ile94, Ile382, Lys374, Val381, Val90, and Tyr34 of the HIV-1 reverse transcriptase (RT), and the molecules were surrounded by other active site residues like Gln332, Trp406, Asn265, Gly93, His96, Pro95, and Thr165. Finally, these novel molecules were analyzed for their pharmacokinetic properties which expressed that the combination of in silico ADMET prediction, toxicity prediction, and drug-likeness had shown a promising result. The study discusses the performance of molecular docking to suggest the novel molecules active against resistance mutants of RT and/or recombinant strains of HIV-1.
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