Synthesis and Evaluation of 1,2,4-oxadiazolidinones: The Search for Potential non-β-lactam β-lactamase Inhibitors.

β-lactam antibiotics have been the most widely used drug of choice to combat infectious disease caused by bacteria. Unfortunately, the effectiveness of these antibiotics is drastically threatened by bacterial β-lactamases. β-lactamases are currently responsible for the resistance to most β-lactam antibiotic drugs. For decades, β-lactam β-lactamases inhibitors have been used to reduce bacterial resistance, however, in this study, we will employ the use of 1,2,4-oxadiazolidinone derivatives as a non-β-lactam β-lactamases inhibitor against TEM-1 and P99 β-lactamases. The significance of oxadiazolidinone is the prominent five-membered ring in its structure, which is configurationally stable and present in other biologically active compounds such as linezolid and avibactam. Oxadiazolidinones were synthesized in two steps procedure using nitroalkanes and benzaldehyde as starting materials to produce nitrones, which in turn undergo 1,3- dipolar cycloaddition with substituted isocyanates to give the desired 1,2,4-oxadiazolidin analogs (2a, 2b, 2c and 3). Each product was purified and characterized using 1H NMR and 13C NMR, GC-MS, IR, and UV/Vis analysis. Following their successful synthesis and structural elucidation, they were tested with TEM-1 and P99 serine β-lactamase using Nitrocefin as the substrate to ascertain their effectiveness against β-lactamase. 2a, 2b, 2c and 3 showed inhibition ranging from 12-38 %

Synthesis and Evaluation of 1,2,4-oxadiazolidinones: The Search for A Potential Non-β-lactam β-lactamase Inhibitors.

β-lactam antibiotics have been the most widely used drug of choice to combat infectious disease caused by bacteria. Unfortunately, their effectiveness is drastically threatened by bacterial β-lactamases. β-lactamases is responsible for the resistance to most antibiotic drugs. For decades, β-lactam β-lactamases inhibitors have been used to reduce bacterial resistance; however, in this study 1,2,4-oxadiazolidinone derivatives as a non-β-lactam β-lactamases inhibitor against TEM-1 and P99 β-lactamases. The significance of oxadiazolidinone is the prominent five-membered ring scaffold in its structure, which is configurationally stable and present in other biologically active compounds such as linezolid and avibactam. Oxadiazolidinones were synthesized by treating nitrones with isocyanates. The synthesized compounds were characterized using 1H and 13C NMR, GC-MS, and FTIR. Afterward, they were tested using Nitrocefin as substrate to determine their effectiveness against TEM-1 and P99 serine β-lactamase. Compound 2a-2c, and 3 showed inhibition ranging from 12-38%

SYNTHESIS AND BIOLOGICAL SIGNIFICANCE OF 1,2,4-OXADIAXOLIDIN-5-ONE

SYNTHESIS AND BILOGICAL SIGNIFICANCE OF 1,2,4-OXADIAXOLIDIN-5-ONE Chimdi kalu, Austin Miller and Dr. Abbas G. Shilabin Department of Chemistry, East Tennessee State University, Johnson City, TN 37614. ABSRTACT Due to the challenge posed by microbial resistance to broad spectrum of antibiotics, there has been a great need to synthesize of a novel compound which has a different mechanism of action on microbial activity. 1,2,4-oxadiaxolidin-5-One constitute an important class of compound with tremendous potential as pharmaceutical and otherwise biologically relevance substance due to the fact that its five member ring is a configurationally stable building block. This unit is found in other compound like alkaloids, with vast medical application. This study describes the synthesis of 1,2,4-oxadiaxolidin-5-one in two-step procedure using nitroethane and benzaldehyde as starting materials to produce nitrone, which in turn undergoes 1,3- dipolar cycloaddition with phenyl isocyanate to give 1,2,4-oxadiaxolidin-5-one. The product was characterized using proton NMR and GC-MS. There is an ongoing investigation on the summary of some important inhibitory activity against class A β-lactamase by 1,2,4-oxadiaxolidin-5-one heterocyclic core structure to provide effective antimicrobial β-lactamase inhibitors, hence, solving the problem of microbial resistance to currently used antimicrobial drugs

Bacterial Communities in Informal Dump Sites: A Rich Source of Unique Diversity and Functional Potential for Bioremediation Applications

In this study, high-throughput metagenomic amplicon sequencing and physicochemical analyses were used to evaluate the structural composition and functional diversity of the soil bacterial communities at different illegal waste dump sites. Results showed that while the litter-free soil was dominated by the phylum Proteobacteria, dumpsite soils were enriched with phylum Actinobacteria, followed by Proteobacteria, Firmicutes, Chloroflexi, Acidobacteria, Planctomycetes, Bacteroidetes, and Gemmatimonadetes. Bacterial diversity differed significantly (p > 0.05) between the litter-free and contaminated sites, with each dumpsite having distinct genera that demonstrate the impact of waste type on the bacterial community composition. Genus Nocardioides, a versatile organic and inorganic pollutant-degrading bacteria in the class Actinomycetia, was dominant in the dump site soils, raising the possibility that this genus could serve as a potential biomarker for dump site soil pollution. PICRUSt functional profiling also showed the presence of genes involved in putative degradative pathways in the dump site soils. Furthermore, community-level physiological profile (CLPP) analyses revealed that the dump site soils are habitats to active bacterial communities with significant catabolic and carbon utilization capacity. Overall, this study provides a theoretical insight into the diversity and unique soil bacterial assemblages in illegal dump sites that could encode biotechnologically significant genes for biosynthesis and biodegradation

Bacterial Communities in Informal Dump Sites: A Rich Source of Unique Diversity and Functional Potential for Bioremediation Applications

In this study, high-throughput metagenomic amplicon sequencing and physicochemical analyses were used to evaluate the structural composition and functional diversity of the soil bacterial communities at different illegal waste dump sites. Results showed that while the litter-free soil was dominated by the phylum Proteobacteria, dumpsite soils were enriched with phylum Actinobacteria, followed by Proteobacteria, Firmicutes, Chloroflexi, Acidobacteria, Planctomycetes, Bacteroidetes, and Gemmatimonadetes. Bacterial diversity differed significantly (p > 0.05) between the litter-free and contaminated sites, with each dumpsite having distinct genera that demonstrate the impact of waste type on the bacterial community composition. Genus Nocardioides, a versatile organic and inorganic pollutant-degrading bacteria in the class Actinomycetia, was dominant in the dump site soils, raising the possibility that this genus could serve as a potential biomarker for dump site soil pollution. PICRUSt functional profiling also showed the presence of genes involved in putative degradative pathways in the dump site soils. Furthermore, community-level physiological profile (CLPP) analyses revealed that the dump site soils are habitats to active bacterial communities with significant catabolic and carbon utilization capacity. Overall, this study provides a theoretical insight into the diversity and unique soil bacterial assemblages in illegal dump sites that could encode biotechnologically significant genes for biosynthesis and biodegradation

Occurrences and implications of pathogenic and antibiotic-resistant bacteria in different stages of drinking water treatment plants and distribution systems

Different stages of drinking water treatment plants (DWTPs) play specific roles in diverse contaminants’ removal present in natural water sources. Although the stages are recorded to promote adequate treatment of water, the occurrence of pathogenic bacteria (PB) and antibiotic-resistant bacteria (ARB) in the treated water and the changes in their diversity and abundance as it passed down to the end users through the drinking water distribution systems (DWDSs), is a great concern, especially to human health. This could imply that the different stages and the distribution system provide a good microenvironment for their growth. Hence, it becomes pertinent to constantly monitor and document the diversity of PB and ARB present at each stage of the treatment and distribution system. This review aimed at documenting the occurrence of PB and ARB at different stages of treatment and distribution systems as well as the implication of their occurrence globally. An exhaustive literature search from Web of Science, Science-Direct database, Google Scholar, Academic Research Databases like the National Center for Biotechnology Information, Scopus, and SpringerLink was done. The obtained information showed that the different treatment stages and distribution systems influence the PB and ARB that proliferate. To minimize the human health risks associated with the occurrence of these PB, the present review, suggests the development of advanced technologies that can promote quick monitoring of PB/ARB at each treatment stage and distribution system as well as reduction of the cost of environomics analysis to promote better microbial analysis