A Retrospective Observational Study of the Microbial Etiology and Antimicrobial Susceptibility Patterns of Blood Cultures From ICU Patients at a Healthcare Facility in North India.

Introduction Bloodstream infections (BSI) are a leading source of fatalities and morbidity in hospitals. However, the clinical spectrum and antimicrobial resistance differ globally. Identifying the pathogenic spectrum and variations in antibiotic resistance is crucial for controlling BSI and preventing inappropriate antibiotic use. Material and methods This retrospective observational study was conducted at the Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, UP, India, for one year between June 2022 and June 2023. A total of 669 adult patients' blood cultures were obtained from ICUs. Blood culture was done using a BacT/Alert 3D (BioMérieux SA, Marcy-l'Étoile, France) automated system. Identification of the bacterial as well as fungal isolates was done using matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS), and the antimicrobial susceptibility profile was analyzed using the VITEK 2 Compact system (BioMérieux SA). Results Of the 669 blood culture samples, 213 (31.8%) showed bacterial or fungal growth. Of these 213 isolates, the most common isolate was coagulase-negative Staphylococci (21.6%), followed by Klebsiella pneumoniae (19.3%) and Acinetobacter spp. (17.8%). The majority of gram-negative bacteria were resistant to most drugs, and vancomycin and linezolid were both effective against the majority of gram-positive bacteria. Conclusion The current study found that septicemia was more frequently caused by gram-negative bacteria than by gram-positive bacteria. Blood cultures are always necessary in cases of suspected septicemia, and once the antimicrobial susceptibility profile of the pathogen causing septicemia has been determined, suitable antimicrobials should be prescribed and used to lower the antimicrobial resistance burden.

Evaluation of Direct Antimicrobial Susceptibility Testing from Positive Flagged Blood Cultures in Sepsis Patients.

Background: Presently, many laboratories are equipped with automated system for antimicrobial susceptibility testing (AST) for minimum inhibitory concentration-based reporting which enables the clinician to choose the right antimicrobial for timely treatment of sepsis. The study aimed to assess performance of direct AST from blood culture positive broth using automated AST system for accuracy and time taken to release the report. Materials and methods: The present study conducted in a 25-bedded ICU in North India for 12 months. Single morphotype of bacteria on gram stain from positively flagged blood culture bottles were included, which was directly identified (using an in-house protocol) with MALDI-TOF-MS from positive blood culture broths. DAST was carried out from 200 such blood culture broths and results were compared with reference AST (RAST) which was also done using VITEK-2 using overnight grown bacterial colonies as per standard protocol. Results: Among 60 isolates of Enterobacterales, 99% categorical agreement for both E. coli and K. pneumoniae observed by two methods were tested for AST. Among non-fermenters, Pseudomonas aeruginosa showed a categorical agreement of 99.6%, as compared with Acinetobacter spp. and exotic GNBs, which showed 95-96% agreement. A significant difference of 18-24 hours was noted in time to release the report between DAST and RAST, for GNB and GPC both. Conclusion: Direct AST from positive flagged blood culture bottles can significantly reduce the time to release the bacterial susceptibility report by up to 24 hours, at the same time maintaining the accuracy. How to cite this article: Singh V, Agarwal J, Nath SS, Sharma A. Evaluation of Direct Antimicrobial Susceptibility Testing from Positive Flagged Blood Cultures in Sepsis Patients. Indian J Crit Care Med 2024;28(4):387-392.

Identification of primary metabolites in fungal species of Trichophyton mentagrophyte and Trichophyton rubrum by NMR spectroscopy.

BACKGROUND: Superficial mycoses are fungal infections limited to the outermost layers of the skin and its appendages. The chief causative agents of these mycoses are dermatophytes and yeasts. The diagnosis of dermatophytosis can be made by direct mycological examination with potassium hydroxide (10%-30%) of biological material obtained from patients with suspected mycosis, providing results more rapid than fungal cultures, which may take days or weeks. This information, together with clinical history and laboratory diagnosis, ensures that the appropriate treatment is initiated promptly. However, false negative results are obtained in 5%-15%, by conventional methods of diagnosis of dermatophytosis. OBJECTIVES: To study the metabolic profiles of the commonly occurring dermatophytes by NMR spectroscopy. PATIENTS/MATERIALS: We have used 1D and 2D Nuclear Magnetic Resonance (NMR) experiments along with Human Metabolome Database (HMDB) and Chenomx database search for identification of primary metabolites in the methanol extract of two fungal species: Trichophyton mentagrophyte (T. mentagrophyte) and Trichophyton rubrum (T. rubrum). Both standard strains and representative number of clinical isolates of these two species were investigated. Further, metabolic profiles obtained were analysed using multivariate analysis. RESULTS: We have identified 23 metabolites in the T. mentagrophyte and another 23 metabolites in T. rubrum. Many important metabolites like trehalose, proline, mannitol, acetate, GABA and several other amino acids were detected, which provide the necessary components for fungal growth and metabolism. Altered metabolites were defined between Trichophyton mentagrophyte and T. rubrum strains. CONCLUSION: We have detected many metabolites in the two fungal species T. mentagrophyte and T. rubrum by using NMR spectroscopy. NMR spectroscopy provides a holistic snapshot of the metabolome of an organism. Key metabolic differences were identified between the two fungal strains. We need to perform more studies on metabolite profiling of the samples from these species for their rapid diagnosis and prompt treatment.

Multielectron Redox Afforded by a Pincer Ligand Promoting Kumada Cross-Coupling Reactions.

The redox-active nature of a pincer has been exploited to conduct C-C cross-coupling reactions under mild conditions. A nickel complex with a NNN pincer was dimeric in the solid state, and the structure displayed a Ni2 N2 diamond core. In the dimeric structure, both ligand backbones house an electron, in the iminosemiquinonate form, to keep the metal's oxidation state at +2. In the presence of an aryl Grignard reagent, only 3 mol % loading the nickel complex generates a Kumada cross-coupled product in good yield from a wide variety of aryl-X (X= I, Br, Cl) substrates. That the ligand-based radical remains responsible for promoting such a coupling reaction following a radical pathway is suggested by TEMPO quenching. Furthermore, a radical-clock experiment along with tracing product distribution unambiguously supported the radical's involvement through the catalytic cycle. A series of thorough mechanistic probation, including computational DFT analysis, disclosed the cooperative action of both redox-active pincer ligand and the metal centre to drive the reaction.

ComplexEye: a multi-lens array microscope for high-throughput embedded immune cell migration analysis.

Autonomous migration is essential for the function of immune cells such as neutrophils and plays an important role in numerous diseases. The ability to routinely measure or target it would offer a wealth of clinical applications. Video microscopy of live cells is ideal for migration analysis, but cannot be performed at sufficiently high-throughput (HT). Here we introduce ComplexEye, an array microscope with 16 independent aberration-corrected glass lenses spaced at the pitch of a 96-well plate to produce high-resolution movies of migrating cells. With the system, we enable HT migration analysis of immune cells in 96- and 384-well plates with very energy-efficient performance. We demonstrate that the system can measure multiple clinical samples simultaneously. Furthermore, we screen 1000 compounds and identify 17 modifiers of migration in human neutrophils in just 4 days, a task that requires 60-times longer with a conventional video microscope. ComplexEye thus opens the field of phenotypic HT migration screens and enables routine migration analysis for the clinical setting.

Precision Covalent Organic Frameworks for Surface Nucleation Control.

Unwanted accumulation of ice and lime scale crystals on surfaces is a long-standing challenge with major economic and sustainability implications. Passive inhibition of icing and scaling by liquid-repellent surfaces are often inadequate, susceptible to surface failure under harsh conditions, and unsuitable for long-term/real-life usages. Such surfaces often require a multiplicity of additional features such as optical transparency, robust impact resistance, and ability to prevent contamination from low surface energy liquids. Unfortunately, most promising advances have relied on using perfluoro compounds, which are bio-persistent and/or highly toxic. Here it is shown that organic, reticular mesoporous structures, covalent organic frameworks (COFs), may offer a solution. By exploiting simple and scalable synthesis of defect-free COFs and rational post-synthetic functionalization, nanocoatings with precision nanoporosity (morphology) are prepared that can inhibit nucleation at the molecular level without compromising the related contamination prevention and robustness. The results offer a simple strategy to exploit the nanoconfinement effect, which remarkably delays the nucleation of ice and scale formation on surfaces. Ice nucleation is suppressed down to -28 °C, scale formation is avoided for >2 weeks in supersaturated conditions, and jets of organic solvents impacting at Weber numbers >105 are resisted with surfaces that also offer optical transparency (>92%).

Synthesis, Biological Evaluation and in Silico Studies of 3-Hydroxy-N-(2-(substituted phenyl)-4-oxothiazolidin-3-yl)-2-napthamide Derivatives.

In the present study, a series of 3-hydroxy-N-(2-(substituted phenyl)-4-oxothiazolidin-3-yl)-2-napthamide derivatives were synthesized, characterized and evaluated for theirin vitroactivity, i. e., antimicrobial, antioxidant and anti-inflammatory. The target compounds were synthesized by condensation reaction of 3-hydroxy-2-naphthoic acid hydrazide with substituted benzaldehydes which were subjected to cyclization reaction with thioglycolic acid and ZnCl2 to get target compounds. The synthesized 3-hydroxy-N-(2-(substituted phenyl)-4-oxothiazolidin-3-yl)-2-napthamide derivatives were examined for their antimicrobial activity and 3-hydroxy-N-(4-oxo-2-(3,4,5-trimethoxyphenyl)thiazolidin-3-yl)-2-naphthamide (S20) exhibited the highest antimicrobial potential. The N'-(2,3-dichlorobenzylidene)-3-hydroxy-2-naphthohydrazide (S5) displayed good antifungal potential against Rhizopus oryzae, whereas N'-(2,3-dichlorobenzylidene)-3-hydroxy-2-naphthohydrazide (S20) showed the highest antioxidant potential and N-(2-(2,6-dichlorophenyl)-4-oxothiazolidin-3-yl)-3-hydroxy-2-naphthamide (S16) displayed the highest anti-inflammatory activity. The results of molecular docking studies revealed that existence of hydrogen bonding and hydrophobic interactions with their respective proteins. In silico ADMET studies were carried out by Molinspiration, Pre-ADMET and OSIRIS property explorer to predict the pharmacokinetic behaviour of synthesized 3-hydroxy-N-(2-(substituted phenyl)-4-oxothiazolidin-3-yl)-2-napthamide derivatives.

Matrix-Assisted Laser Desorption Ionization Time of Flight (MALDI-TOF) as an Indispensable Tool in Diagnostic Bacteriology: A Comparative Analysis With Conventional Technique.

INTRODUCTION: Owing to its accurate diagnosis, rapid turnaround time, cost effectivity, and less rates of error, Matrix-assisted Laser Desorption Ionization Time of Flight (MALDI-TOF) has replaced most of the phenotypic methods of identification. Thus, the objective of this study was to compare and evaluate MALDI-TOF MS to conventional biochemical-to identify bacterial microorganisms. METHODS: Different bacterial species isolated from 2010 to 2018 (pre-MALDI-TOF era), using routine bio-chemicals were compared to bacterial species isolated from 2019 to August 2021 (post MALDI-TOF), using MALDI-TOF, in the microbiology laboratory of a tertiary care hospital in North India. Chi-Square test (χ2) was used for the evaluation of bacterial identification between biochemical tests and MALDI-TOF MS association with a 95% confidence interval, considering wrong identification in genera or at a species level. RESULTS: Many different and new genera and species of bacteria could be identified using MALDI-TOF, which was not possible using only routine manual bio-chemicals like Kocuria rhizophilus, Rothia mucilaginosa, Enterococcus casseliflavus, Enterococcus gallinarum, Leuconostoc, Leclercia adecarboxylata, Raoultella ornithological, Cryseobacterium indologenes. Conclusion: Each of the newly identified bacteria played an important role in deciding treatment. Wide use of the MALDI-TOF system will not only strengthen diagnostic stewardship but also encourage antimicrobial stewardship programs.

Unexplored Facet of Pincer Ligands: Super-Reductant Behavior Applied to Transition-Metal-Free Catalysis.

Pincer ligands are well-established supporting ancillaries to afford robust coordination to metals across the periodic table. Despite their widespread use in developing homogeneous catalysts, the redox noninnocence of the ligand backbone is less utilized in steering catalytic transformations. This report showcases a trianionic, symmetric NNN-pincer to drive C-C cross-coupling reactions and heterocycle formation via C-H functionalization, without any coordination to transition metals. The starting substrates are aryl chlorides that can tease the limit of a catalyst's ability to promote a reductive cleavage at a much demanding potential of -2.90 V vs SCE. The reducing power of the simple trianionic ligand backbone has been tremendously amplified by shining visible light on it. The catalyst's success relies on its easy access to the one-electron oxidized iminosemiquinonate form that has been thoroughly characterized by X-band electron paramagnetic resonance spectroscopy through spectroelectrochemical experiments. The moderately long-lived excited-state lifetime (10.2 ns) and such a super-reductive ability dependent on the one-electron redox shuttle between the bisamido and iminosemiquinonato forms make this catalysis effective.

Alzheimer's disease: Molecular aspects and treatment opportunities using herbal drugs.

Alzheimer's disease (AD), also called senile dementia, is the most common neurological disorder. Around 50 million people, mostly of advanced age, are suffering from dementia worldwide and this is expected to reach 100-130 million between 2040 and 2050. AD is characterized by impaired glutamatergic and cholinergic neurotransmission, which is associated with clinical and pathological symptoms. AD is characterized clinically by loss of cognition and memory impairment and pathologically by senile plaques formed by Amyloid ß deposits or neurofibrillary tangles (NFT) consisting of aggregated tau proteins. Amyloid ß deposits are responsible for glutamatergic dysfunction that develops NMDA dependent Ca2+ influx into postsynaptic neurons generating slow excitotoxicity process leading to oxidative stress and finally impaired cognition and neuronal loss. Amyloid decreases acetylcholine release, synthesis and neuronal transport. The decreased levels of neurotransmitter acetylcholine, neuronal loss, tau aggregation, amyloid ß plaques, increased oxidative stress, neuroinflammation, bio-metal dyshomeostasis, autophagy, cell cycle dysregulation, mitochondrial dysfunction, and endoplasmic reticulum dysfunction are the factors responsible for the pathogenesis of AD. Acetylcholinesterase, NMDA, Glutamate, BACE1, 5HT6, and RAGE (Receptors for Advanced Glycation End products) are receptors targeted in treatment of AD. The FDA approved acetylcholinesterase inhibitors Donepezil, Galantamine and Rivastigmine and N-methyl-D-aspartate antagonist Memantine provide symptomatic relief. Different therapies such as amyloid ß therapies, tau-based therapies, neurotransmitter-based therapies, autophagy-based therapies, multi-target therapeutic strategies, and gene therapy modify the natural course of the disease. Herbal and food intake is also important as preventive strategy and recently focus has also been placed on herbal drugs for treatment. This review focuses on the molecular aspects, pathogenesis and recent studies that signifies the potential of medicinal plants and their extracts or chemical constituents for the treatment of degenerative symptoms related to AD.

Rapid and fully automated blood vasculature analysis in 3D light-sheet image volumes of different organs.

Light-sheet fluorescence microscopy (LSFM) can produce high-resolution tomograms of tissue vasculature with high accuracy. However, data processing and analysis is laborious due to the size of the datasets. Here, we introduce VesselExpress, an automated software that reliably analyzes six characteristic vascular network parameters including vessel diameter in LSFM data on average computing hardware. VesselExpress is ∼100 times faster than other existing vessel analysis tools, requires no user interaction, and integrates batch processing and parallelization. Employing an innovative dual Frangi filter approach, we show that obesity induces a large-scale modulation of brain vasculature in mice and that seven other major organs differ strongly in their 3D vascular makeup. Hence, VesselExpress transforms LSFM from an observational to an analytical working tool.

Self-Healing, Robust, Liquid-Repellent Coatings Exploiting the Donor-Acceptor Self-Assembly.

Liquid-repellent coatings with rapid self-healing and strong substrate adhesion have tremendous potential for industrial applications, but their formulation is challenging. We exploit synergistic chemistry between donor-acceptor self-assembly units of polyurethane and hydrophobic metal-organic framework (MOF) nanoparticles to overcome this challenge. The nanocomposite features a nanohierarchical morphology with excellent liquid repellence. Using polyurethane as a base polymer, the incorporated donor-acceptor self-assembly enables high strength, excellent self-healing property, and strong adhesion strength on multiple substrates. The interaction mechanism of donor-acceptor self-assembly was revealed via density functional theory and infrared spectroscopy. The superhydrophobicity of polyurethane was achieved by introducing alkyl-functionalized MOF nanoparticles and post-application silanization. The combination of the self-healing polymer and nanohierarchical MOF nanoparticles results in self-cleaning capability, resistance to tape peel and high-speed liquid jet impacts, recoverable liquid repellence over a self-healed notch, and low ice adhesion up to 50 icing/deicing cycles. By exploiting the porosity of MOF nanoparticles in our nanocomposites, fluorine-free, slippery liquid-infused porous surfaces with stable, low ice adhesion strengths were also achieved by infusing silicone oil into the coatings.

Sustainable γ-cyclodextrin frameworks containing ultra-fine silver nanoparticles with enhanced antimicrobial efficacy.

Cyclodextrin metal-organic frameworks (CD-MOF) are a class of biocompatible MOF with a great potential in drug delivery applications. Original CD-MOF crystals are fragile and large (0.2-1 mm), which are less useful in pharmaceutical applications. Cetyltrimethylammonium bromide and long chain poly(ethylene) glycol, used in size modulation to produce nanosized CD-MOF can compromise the biocompatibility, and physiochemical properties of CD-MOF as their complete removal from frameworks is difficult. To avoid the use of above-mentioned modulators, herein, we demonstrate the synthesis of nanosized CD-MOF using triethylamine (TEA) as a modulator to reduce their size to ~254 nm. The MOF characteristics such as crystal and chemical structure remain unaffected and the surface area of CD-MOF synthesised with TEA is measured 1075.5 m2/g, almost 50 % higher than those of synthesised using bulky modulators. The improved CD-MOF architecture utilized for the in-situ synthesis of silver nanoparticles resulted in enhanced antimicrobial efficacy tested against Staphylococcus aureus and Escherichia coli bacteria and Candida albicans fungus. And minimum inhibitory concentration (MIC) is recorded in the range of 31-15 µg/mL. Overall, the structural improvement in CD-MOF supported with thorough comparative investigations and enhanced antimicrobial efficacy could be very helpful in further establishing them in biomedicine field.

A retrospective analysis of the 5-year trends of antimicrobial resistance in gram-negative bacterial isolates from an intensive care unit at a tertiary care hospital.

Background: Intensive care units (ICUs) in developing countries constitute a high risk for patients acquiring infection by multidrug-resistant organisms (MDROs). The rise in antimicrobial resistance (AMR) threatens the effective prevention and treatment of an increasing range of infections. The present study analyzed the local trends of AMR in Gram-negative isolates of ICU patients from a tertiary care facility in North India. Methods: This retrospective study was conducted over 5 years (January 2018-December 2022). All bacterial isolates from patients admitted to ICU during the study period were included in the study, and their AMR pattern was analyzed. In addition, sensitivity trends of different antimicrobials against the common Gram-negative bacteria were analyzed, and AMR trends were analyzed over the study period. Results: Klebsiella spp. was the most common isolate in samples received from ICU. A rise of carbapenem-resistant microorganisms was observed over the study period. Escherichia coli and Klebsiella spp. showed around 10% and a 17% decrease in susceptibility to carbapenems, respectively. In contrast, a marked 29% decrease in sensitivity to carbapenems was observed in Acinetobacter spp. Conclusion: The inception of integrated stewardship measures has shown a rising trend in susceptibility and is the need of the hour to prevent the spread of MDROs. Surveillance studies help us understand the impact of AMR in hospitals and help plan prevention programs.

Synthesis, in silico studies and biological screening of (E)-2-(3-(substitutedstyryl)-5-(substitutedphenyl)-4,5-dihydropyrazol-1-yl)benzo[d]thiazole derivatives as an anti-oxidant, anti-inflammatory and antimicrobial agents.

A new series of (E)-2-(3-(substitutedstyryl)-5-(substitutedphenyl)-4,5-dihydropyrazol-1-yl)benzo[d]thiazole derivatives was synthesized and the chemical structures of synthesized compounds were deduced by IR and NMR spectral tools. These compounds were synthesized via aldol condensation reaction of substituted benzaldehydes and acetone in alkaline ethanolic solution and their in vitro anti-oxidant, anti-inflammatory and antimicrobial activities were investigated. All the synthesized compounds displayed anti-oxidant potential with IC50 values ranging from 0.13 to 8.43 µmol/ml. The compound Z13 exhibited potent anti-inflammatory activity with IC50 value of 0.03 µmol/ml compared with the standard ibuprofen, which showed IC50 value of 0.11 µmol/ml. On the other hand, most of the compounds had a certain antibacterial potential particularly against P. aeruginosa and among these derivatives, compound Z2 exhibited the highest potential against P. aeruginosa with MIC value of 0.0069 µmol/ml. The analysis of docking results demonstrated the binding affinity and hydrogen bond, electrostatic and hydrophobic interactions of all the synthesized compounds with their respective targets. In silico ADMET studies were carried out for the synthesized compounds and most of the compounds exhibited good ADMET profile.

Ischemic stroke and concomitant gastrointestinal complications- a fatal combination for patient recovery.

Stroke is primarily a neurodegenerative disease but can also severely impact the functions of other vital organs and deteriorate disease outcomes. A malfunction of the gastrointestinal tract (GIT), commonly observed in stroke patients, is often characterized by severe bowel obstruction, intestinal microbiota changes and inflammation. Over-activated immune cells after stroke are the major contributors to endorse intestinal inflammation and may induce damage to single-layer epithelial cell barriers. The post-stroke leakage of intestinal barriers may allow the translocation and dissemination of resident microflora to systemic organs and cause sepsis. This overshooting systemic immune reaction fuels ongoing inflammation in the degenerating brain and slows recovery. Currently, the therapeutic options to treat these GIT-associated anomalies are very limited and further research is required to develop novel treatments. In this mini-review, we first discuss the current knowledge from clinical studies and experimental stroke models that provide strong evidence of the existence of post-stroke GIT complications. Then, we review the literature regarding novel therapeutic approaches that might help to maintain GIT homeostasis and improve neurological outcomes in stroke patients.

Synthesis and Biological Evaluation of 2-(Halophenyl)benzoxazole-5-Carboxylic Acids as Potential Anti-Inflammatory and Cytotoxic Agent with Molecular Docking Studies.

2-Halogenatedphenyl benzoxazole-5-carboxylic acids with mono-halogen (chloro, bromo and fluoro) substituted at ortho-, meta- and para-positions on the phenyl ring were designed and synthesized based on significance of presence of halogen in increasing number of marketed halogenated drugs and importance of benzoxazoles. These 2-alogenatedphenylbenzoxazole-5-carboxylic acids and their methyl esters were screened for anti-inflammatory activity, and cytotoxicity. 2-(3-Chlorophenyl)benzoxaole-5-carboxylic acid (6b) exhibited significant anti-inflammatory activity with IC50 values of 0.103 mM almost equivalent to the standard drug ibuprofen (0.101 mM). 2-(4-Chlorophenyl)benzoxaole-5-carboxylic acid (6c) showed excellent cytotoxic activity against 22Rv1 cells (human prostate carcinoma epithelial cell lines) with IC50 value of 1.54 µM better than that of standard drug doxorubicin having IC50 value of 2.32 µM. More importantly, the selectivity index of this potential molecule was found to be 57.74. Molecular docking analysis resulted in good binding interactions of these compounds with their respective biochemical targets viz. Cyclooxygenase-2 and aldo-keto reductase IC3.

Synthesis, Biological Activity and Molecular Docking Studies of Heterocyclic Chalcones.

Nineteen heterocyclic chalcones were synthesized from 4-acetyl-5-methylquinolylpyrazole and heteroaryl (imidazole, pyrazole, thiophene, indole and triazole) aldehydes and were screened in vitro using four tumor cell lines for their cytotoxic capability and for antimicrobial activity. The chalcone 5b exhibited the highest activity with IC50 values 2.14 µM against colon (HCT-116) and 5.0 µM, against prostate (PC-3) cancer cell lines and also displayed good activity against fungal strain (A. niger) with MIC value 9.1 µM. The chalcones 5q and 5p displayed good activity against bacterial strains (S. aureus) having MIC value 2.6 µM and fungal strain (C. albicans) having MIC value 5.4 µM, respectively. The molecular docking outcome revealed that the synthesized heterocyclic chalcones demonstrated hydrogen bond, hydrophobic and electrostatic interactions with their respective biochemical targets.

1,3,4-oxadiazole derivatives as potential antimicrobial agents.

Due to the emergence of drug-resistant microbial strains, different research groups are continuously developing novel drug molecules against already exploited and unexploited targets. 1,3,4-Oxadiazole derivatives exhibited noteworthy antimicrobial activities. The presence of 1,3,4-oxadiazole moiety in antimicrobial agents can modify their polarity and flexibility, which significantly improves biological activities due to various bonded and non-bonded interactions viz. hydrogen bond, steric, electrostatic, and hydrophobic with target sites. The present review elaborates the therapeutic targets and mode of interaction of 1,3,4-oxadiazoles as antimicrobial agents. 1,3,4-oxadiazole derivatives target enoyl reductase (InhA), 14α-demethylase in the mycobacterial cell; GlcN-6-P synthase, thymidylate synthase, peptide deformylase, RNA polymerase, dehydrosqualene synthase in bacterial strains; ergosterol biosynthesis pathway, P450-14α demethylase, protein-N-myristoyltransferase in fungal strains; FtsZ protein, interfere with purine and functional protein synthesis in plant bacteria. The present review also summarizes the effect of different moieties and functional groups on the antimicrobial activity of 1,3,4-oxadiazole derivatives.

Flavonoids, alkaloids and terpenoids: a new hope for the treatment of diabetes mellitus.

Diabetes mellitus is a metabolic syndrome characterized by a hyperglycemic state and multi-organ failure. Millions of people worldwide are suffering from this deadly disease taking a hit on their pocket and mental health in the name of its treatment. Modern medical practices with new technological advancements and discoveries have made revolutionary changes in the treatment. But, unfortunately, Glucose-lowering drugs used have many accompanying effects such as chronic vascular disease, renal malfunction, liver disease and, many skin problems. These complications have made us think about alternative treatments for diabetes with minimum or no side effects. Nowadays, in addition to modern medicine, herbal treatment has been suggested to treat diabetes mellitus. These herbal medicines contain biological macromolecules such as flavonoids, Terpenoids, glycosides, and alkaloids, which show versatile anti-diabetic effects. These phytochemicals are generally considered safe, and naturally occurring compounds have a potential role in preventing or controlling diabetes mellitus. The underlying mechanism of their anti-diabetic effects includes improvement in insulin secretion, decrease in insulin resistance, enhanced liver glycogen synthesis, antioxidant and anti-inflammatory activities. In this review, we have focused on the mechanism of various phytochemicals targeting hyperglycemia and its underlying pathogenesis.