Synthesis and mechanistic studies of diketo acids and their bioisosteres as potential antibacterial agents

A series of diketo esters and their pertinent bioisosteres were designed and synthesized as potent antibacterial agents by targeting methionine amino peptidases (MetAPs). In the biochemical assay against purified MetAPs from Streptococcus pneumoniae (SpMetAP1a), Mycobacterium tuberculosis (MtMetAP1c), Enterococcus faecalis (EfMetAP1a) and human (HsMetAP1b), compounds 3a, 4a and 5a showed more than 85% inhibition of all the tested MetAPs at 100 μM concentration. Compounds 4a and 5a also exhibited antibacterial potential with MIC values 62.5 μg/mL (S. pneumoniae), 31.25 μg/mL (E. faecalis), 62.5 μg/mL (Escherichia coli) and 62.5 μg/mL (S. pneumoniae), 62.5 μg/mL (E. coli), respectively. Moreover, 5a also significantly inhibited the growth of multidrug resistant E. coli strains at 512 μg/mL conc., while showing no cytotoxic effect towards healthy CHO cells and thus being selected. Growth kinetics study showed significant inhibition of bacterial growth when treated with different conc. of 5a. TEM analysis also displayed vital damage to bacterial cells by 5a at MIC conc. Moreover, significant inhibition of biofilm formation was observed in bacterial cells treated with MIC conc. of 5a as visualized by SEM micrographs. Interestingly, 5a did not cause an alteration in the hemocyte density in Galleria mellonella larvae which is considered in vivo model for antimicrobial studies and was non-toxic up to a conc. of 2.5 mg/mL

Heavy Metals and Human Health: Mechanistic Insight into Toxicity and Counter Defense System of Antioxidants

Heavy metals, which have widespread environmental distribution and originate from natural and anthropogenic sources, are common environmental pollutants. In recent decades, their contamination has increased dramatically because of continuous discharge in sewage and untreated industrial effluents. Because they are non-degradable, they persist in the environment; accordingly, they have received a great deal of attention owing to their potential health and environmental risks. Although the toxic effects of metals depend on the forms and routes of exposure, interruptions of intracellular homeostasis include damage to lipids, proteins, enzymes and DNA via the production of free radicals. Following exposure to heavy metals, their metabolism and subsequent excretion from the body depends on the presence of antioxidants (glutathione, α-tocopherol, ascorbate, etc.) associated with the quenching of free radicals by suspending the activity of enzymes (catalase, peroxidase, and superoxide dismutase). Therefore, this review was written to provide a deep understanding of the mechanisms involved in eliciting their toxicity in order to highlight the necessity for development of strategies to decrease exposure to these metals, as well as to identify substances that contribute significantly to overcome their hazardous effects within the body of living organisms

Analysis for the presence of determinants involved in the transport of mercury across bacterial membrane from polluted water bodies of India

Abstract Mercury, which is ubiquitous and recalcitrant to biodegradation processes, threatens human health by escaping to the environment via various natural and anthropogenic activities. Non-biodegradability of mercury pollutants has necessitated the development and implementation of economic alternatives with promising potential to remove metals from the environment. Enhancement of microbial based remediation strategies through genetic engineering approaches provides one such alternative with a promising future. In this study, bacterial isolates inhabiting polluted sites were screened for tolerance to varying concentrations of mercuric chloride. Following identification, several Pseudomonas and Klebsiella species were found to exhibit the highest tolerance to both organic and inorganic mercury. Screened bacterial isolates were examined for their genetic make-up in terms of the presence of genes (merP and merT) involved in the transport of mercury across the membrane either alone or in combination to deal with the toxic mercury. Gene sequence analysis revealed that the merP gene showed 86–99% homology, while the merT gene showed >98% homology with previously reported sequences. By exploring the genes involved in imparting metal resistance to bacteria, this study will serve to highlight the credentials that are particularly advantageous for their practical application to remediation of mercury from the environment

Development of Two-Tube Loop-Mediated Isothermal Amplification Assay for Differential Diagnosis of Plasmodium falciparum and Plasmodium vivax and Its Comparison with Loopamp™ Malaria

To strengthen malaria surveillance, field-appropriate diagnostics requiring limited technical resources are of critical significance. Loop-mediated isothermal amplification (LAMP) based malaria diagnostic assays are potential point-of-care tests with high sensitivity and specificity and have been used in low-resource settings. Plasmodium vivax–specific consensus repeat sequence (CRS)-based and Plasmodium falciparum–specific 18S rRNA primers were designed, and a two-tube LAMP assay was developed. The diagnostic performance of a closed-tube LAMP assay and Loopamp™ Malaria Detection (Pan/Pf, Pv) kit was investigated using nested PCR confirmed mono- and co-infections of P. vivax and P. falciparum positive (n = 149) and negative (n = 67) samples. The closed-tube Pv LAMP assay showed positive amplification in 40 min (limit of detection, LOD 0.7 parasites/µL) and Pf LAMP assay in 30 min (LOD 2 parasites/µL). Pv LAMP and Pf LAMP demonstrated a sensitivity and specificity of 100% (95% CI, 95.96–100% and 89.85–100%, respectively). The LoopampTM Pan/Pf Malaria Detection kit demonstrated a sensitivity and specificity of 100%, whereas LoopampTM Pv showed a sensitivity of 98.36% (95% CI, 91.28–99.71%) and specificity of 100% (95% CI, 87.54–100%). The developed two-tube LAMP assay is highly sensitive (LOD ≤ 2 parasite/µL), demonstrating comparable results with the commercial Loopamp™ Malaria Detection (Pf/pan) kit, and was superior in detecting the P. vivax co-infection that remained undetected by the Loopamp™ Pv kit. The developed indigenous two-tube Pf/Pv malaria detection can reliably be used for mass screening in resource-limited areas endemic for both P. falciparum and P. vivax malaria

Antibacterial Functionalization and Simultaneous Coloration of Wool Fiber with the Application of Plant-Based Dyes

High susceptibility of wool toward bacterial growth owing to proteinous nature and moisture retention ability leads to need for antibacterial functionalization of wool to cure the resulting deterioration. Antibacterial colored wool was designed via application of Terminalia chebula, Alkanna tinctoria, and Tagetes erecta natural dyes. Characteristics in terms of color and antibacterial activity were compared to correlate coloring compound’s effect on characteristics of dyes and, both T. chebula and A. tinctoria dyes inferred themselves actively resisting bacterial growth while T. erecta was not efficient against bacterial strains. Colorful shades of good color and fastness properties were obtained from selected natural dyes on woolen yarn. Results show Bacillus subtilis and Staphylococcus aureus (gram positive) were highly resisted by the effect of T. chebula and A. tinctoria dyes, and T. chebula among them proved best in terms of both color characteristics and antibacterial potential

Diagnostic Performance of Dengue Virus Envelope Domain III in Acute Dengue Infection

Dengue, one of the most prevalent illnesses caused by dengue viruses that are members of the genus Flavivirus, is a significant global health problem. However, similar clinical symptoms and high antigenic homologies with other Flaviviruses in the endemic area pose difficulties for differential diagnosis of dengue from other arbovirus infections. Here, we investigated four types of recombinant envelope protein domain III (DV-rED III) derived from four dengue virus (DENV) serotypes for diagnostic potential in detecting IgM in acute phase (mainly 2–3 days after onset of fever). Each independent DV-1, -3, and -4-rED III-ELISA showed less than 60% sensitivity, but the combined results of DV-1, -3, and -4-rED III-ELISA led to sensitivity of 81.82% (18/22) (95% CI, 59.72 to 94.81) and 100% specificity (46/46) (95% CI, 92.29 to 100.00) as each antigen compensated the other antigen-derived negative result. In conclusion, the independent combination of data derived from each recombinant antigen (DV1-, DV3-, and DV4-rED III) showed comparable efficacy for the detection of IgM in patients with acute-phase dengue infection

Perspective Insights into Disease Progression, Diagnostics, and Therapeutic Approaches in Alzheimer's Disease: A Judicious Update

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the progressive accumulation of β-amyloid fibrils and abnormal tau proteins in and outside of neurons. Representing a common form of dementia, aggravation of AD with age increases the morbidity rate among the elderly. Although, mutations in the ApoE4 act as potent risk factors for sporadic AD, familial AD arises through malfunctioning of APP, PSEN-1, and−2 genes. AD progresses through accumulation of amyloid plaques (Aβ) and neurofibrillary tangles (NFTs) in brain, which interfere with neuronal communication. Cellular stress that arises through mitochondrial dysfunction, endoplasmic reticulum malfunction, and autophagy contributes significantly to the pathogenesis of AD. With high accuracy in disease diagnostics, Aβ deposition and phosphorylated tau (p-tau) are useful core biomarkers in the cerebrospinal fluid (CSF) of AD patients. Although five drugs are approved for treatment in AD, their failures in achieving complete disease cure has shifted studies toward a series of molecules capable of acting against Aβ and p-tau. Failure of biologics or compounds to cross the blood-brain barrier (BBB) in most cases advocates development of an efficient drug delivery system. Though liposomes and polymeric nanoparticles are widely adopted for drug delivery modules, their use in delivering drugs across the BBB has been overtaken by exosomes, owing to their promising results in reducing disease progression

Antimicrobial and fluorescence finishing of woolen yarn with Terminalia arjuna natural dye as an ecofriendly substitute to synthetic antibacterial agents

The current study deals with the use of Terminalia arjuna natural dye as an ecofriendly finishing agent for producing highly functional antimicrobial and fluorescent woolen yarn along with the evaluation of kinetic and thermodynamic adsorption characteristics. The effect of pH on the adsorption was investigated, showing an increase in adsorption capacity with decreasing pH over the range of 2–9, with maximum adsorption at pH 3.5. Two kinetic equations pseudo-first order and pseudo-second order were employed for determining adsorption rates. The pseudo-second order equation provided the best fit to experimental data with an activation energy of 105.58 kJ mol−1, indicating chemisorption. The equilibrium adsorption data was fitted to Langmuir, Freundlich and Redlich–Peterson adsorption isotherms. The adsorption behavior accorded with the Redlich–Peterson isotherm with exceptionally high regression coefficients for dyeing temperatures of 50, 70 and 90 °C with dye concentration varying from 0.5–10% (o.w.f). Comparative results of the colorimetric properties (CIEL*a*b* and K/S) using a spectrophotometer under D65 illuminant (10° standard observer) and color fastness (light, wash, and rub) of dyed woolen yarns were studied to quantify the effect of metal mordants. The antimicrobial potential of Terminalia arjuna solution and dyed woolen yarn were assessed in terms of percentage inhibition of bacterial growth against a wide variety of bacterial strains, showing more than 85% inhibition. Reduction in antimicrobial activity of dyed woolen yarn was observed with mordanted samples, however they were found to retain more antimicrobial activity as compared to unmordanted samples as a function of successive washing cycles. The chemical nature of different mordants and wool–mordant–dye complex forming ability were found to have significant impact on the colorimetric and fluorescence characteristics of dyed woolen yarn