Identification of Chemical Scaffolds Targeting Drug-Resistant and Latent through High-Throughput Whole-Cell Screening.

Identification of structurally unique chemical entities targeting unexplored bacterial targets is a prerequisite to combat increasing drug resistance against . This study employed a whole-cell screening approach as an initial filter to scrutinize a 10,000-compound chemical library, resulting in the discovery of seven potent compounds with MIC values ranging from 1.56 to 25 μM.

A checklist of epibiont and parasite ciliates (Ciliophora) associated to rotifers (Rotifera).

A review of the ciliate (Ciliophora) species associated to rotifers as epibionts and endoparasites is presented, based on published records. Thirty rotifer species from 12 genera are known as hosts of ciliates. Among ciliates, one species of class Suctorea and 14 species of class Oligohymenophorea (12 from subclass Peritrichia, one from Hymenostomatia, and one from Astomatia) have been noted as associated to rotifers.

Design, synthesis, and pharmacological evaluation of indole-piperidine amides as Blood-brain barrier permeable dual cholinesterase and β-secretase inhibitors.

Heterocyclic compounds play a crucial role in the discovery of therapeutics. Alzheimer's disease (AD) is an unfathomable sporadic neurodegenerative disorder that involves multiple pathological pathways. The failure of current single-target small molecules to address AD's underlying causes has prompted interest in discovering multi-target directed ligands (MTDLs) to slow down the disease's progression.

Brønsted acid- and Ni(II)-catalyzed C-H oxidation/rearrangement of cyclotriveratrylenes (CTVs) to cyclic and acyclic quinones as potential anti-cancer agents.

This paper describes a simple and practical protocol for the direct synthesis of acyclic and cyclic quinone derivatives an acid-promoted nickel(II)-catalyzed inner rim C-H oxidation of cyclotriveratrylene (CTV) and its analogues. The cyclic quinone derivatives resulted from trimethoxy-cyclotriveratrylene (TCTV) through C-C bond formation intramolecular substitution followed by subsequent anionic rearrangement containing stereo-vicinal quaternary centers. The DFT calculations strongly support the experimental findings and reveal the role of Brønsted acids in the C-H bond activation of CTV.

Trilliumosides K and L, two novel steroidal saponins from rhizomes of , as potent anti-cancer agents targeting apoptosis in the A-549 cancer cell line.

Two novel steroidal saponins, trilliumosides K () and L (), were isolated from the rhizomes of led by bioactivity-guided phytochemical investigation along with seven known compounds: govanoside D (), protodioscin (), borassoside E (), 20-hydroxyecdysone (), 5,20-hydroxyecdysone (), govanic acid (), and diosgenin (). The structure of novel compounds 1-2 was established using analysis of spectroscopic data including 1D and 2D nuclear magnetic resonance (NMR) and high resolution mass spectrometry (HR-ESI-MS) data. All isolated compounds were evaluated for cytotoxic activity against a panel of human cancer cell lines.

Sustained release polymer and surfactant based solid dispersion of andrographolide exhibited improved solubility, dissolution, pharmacokinetics, and pharmacological activity.

Andrographolide (AD) is a potent natural product with a wide range of pharmacological activities. However, it has low oral bioavailability due to poor solubility and dissolution rate. Solid dispersion (SD) is a promising technique to improve the solubility and dissolution rate of such molecules.

CstMYB1R1, a REVEILLE-8-like transcription factor, regulates diurnal clock-specific anthocyanin biosynthesis and response to abiotic stress in Crocus sativus L.

CstMYB1R1 acts as a positive regulator of Crocus anthocyanin biosynthesis and abiotic stress tolerance which was experimentally demonstrated through molecular analysis and over-expression studies in Crocus and Nicotiana. Regulatory mechanics of flavonoid/anthocyanin biosynthesis in Crocus floral tissues along the diurnal clock has not been studied to date. MYB proteins represent the most dominant, functionally diverse and versatile type of plant transcription factors which regulate key metabolic and physiological processes in planta.

Enrichment of Native and Recombinant Extracellular Vesicles of Mycobacteria.

Most bacteria, including mycobacteria, generate extracellular vesicles (EVs). Since bacterial EVs (bEVs) contain a subset of cellular components, including metabolites, lipids, proteins, and nucleic acids, several groups have evaluated either the native or recombinant versions of bEVs for their protective potency as subunit vaccine candidates. Unlike native EVs, recombinant EVs are molecularly engineered to contain one or more immunogens of interest.

Metarhabditis amsactae: A potential biopesticide isolated from Punjab (India) with potent insecticidal activity and immunomodulatory effects against Galleria mellonella (Lepidoptera: Pyralidae).

A survey was undertaken to isolate entomopathogenic nematodes from Amritsar district of Punjab, India. Out of 20 soil samples collected, two were found positive for the presence of nematodes. 18S and ITS rDNA gene sequencing revealed their identity as Metarhabditis amsactae.

The significance of persisters in tuberculosis drug discovery: Exploring the potential of targeting the glyoxylate shunt pathway.

The significant challenge in confronting TB eradication is the discursive treatment that results in the disease reactivation, patient non compliance and drug resistance. The presently available drug regimen for TB largely targets the active bacilli and thus remains inadequate against the dormant or persistent subpopulation of Mtb that results in latent TB affecting a quarter of the global population. The crucial pathways that are particularly essential for the survival of dormant Mtb demand better apprehension.

Sila-CBD Derivatives as Inhibitors of Heme-Induced NLRP3 Inflammasome: Application in Hemolytic Diseases.

Synthesis and biological evaluation of silicon-incorporated phytocannabinoids with improved pharmacological properties toward inflammatory diseases are described. The synthesized sila-analogues , , and displayed potent inhibition of pro-inflammatory cytokines, including IL-1β, TNF-α, and IL-6 at 10 μM. Further, the release of heme during the lysis of red blood cells in hemolytic diseases is one of the major reasons for inflammation associated with the pathophysiology of these diseases.

Divergent synthesis of fractionated Cannabis sativa extract led to multiple cannabinoids C-&O-glycosides with anti-proliferative/anti-metastatic properties.

Here, we present an interesting, previously unreported method for fractionating a particular class of cannabinoids from the crude leaf extract of Cannabis sativa using HP-20 resins. In this study, we report a novel method of divergent synthesis of fractionated Cannabis sativa extract, which allows the generation of multiple cannabinoids C- and O-glycosides which react with the glycosyl donor 2,3,4,6-tetra-O-acetyl-d-mannosyl trichloroacetimidate (TAMTA) to create eight C- and O-β-d-cannabinoids glycosides (COCG), which are separated by HPLC and whose structures are characterized by 1D, 2D NMR, and mass spectrometry. These glycosides exhibit improved anti-proliferative and anti-metastatic effects against numerous cancer cell lines in vitro and are more water-soluble and stable than their parent cannabinoids.

Synthesis of mixed phosphorotrithioates thiol coupling with bis(diisopropylamino)chlorophosphine and sulphenyl chloride.

In this study, we report a novel and efficient one-pot synthesis of mixed phosphorotrithioates under mild conditions at ambient temperature, obviating the requirement for supplementary additives. The method's versatility stems from its utilization of diverse thiols as nucleophilic reactants, 1-chloro-,,','-tetraisopropylphosphanediamine [bis(diisopropylamino)chlorophosphine] as the phosphorus precursor, and various sulphenyl chlorides as sources of electrophilic sulfur. Notably, our investigation extends beyond mixed phosphorotrithioates to encompass the synthesis of phosphoroselenodithioates, underscoring the broad applicability of this synthetic protocol.

An atypical heterotrimeric Gα and its interactome suggest an extra-large role in overcoming abiotic and biotic stress.

Canonical heterotrimeric G-proteins (G-proteins) are comprised of Gα, Gβ, and Gγ subunits. G-proteins regulate multiple crucial plant growth and development processes, incorporating environmental responses. Besides Gα, Gβ and Gγ, the discovery of atypical Gα subunits termed as extra-large G-proteins or extra-large GTP-binding proteins (XLGs) makes G-protein signaling unique in plants.

Association of the gene variant rs9940180 with schizophrenia risk in North Indian population.

Background And Objectives: Cadherin13 () is an uncommon cadherin family member, lacking a transmembrane domain, and attaches via a glycosylphosphatidylinositol anchor to the peripheral surface of the cell membrane. plays an important role in the development and maintenance of axonal growth cones, synapse morphogenesis, and the embryonic neural tube. Cadherin superfamily genes have been associated with many neuropsychiatric diseases.

A comprehensive review of genomics, transcriptomics, proteomics, and metabolomic insights into the differentiation of Pseudomonas aeruginosa from the planktonic to biofilm state: A multi-omics approach.

Biofilm formation by Pseudomonas aeruginosa is primarily responsible for chronic wound and lung infections in humans. These infections are persistent owing to the biofilm's high tolerance to antimicrobials and constantly changing environmental factors. Understanding the mechanism governing biofilm formation can help to develop therapeutics explicitly directed against the molecular markers responsible for this process.

Multifunctional apple seed protein hydrolysates: Impact of enzymolysis on the biochemical, techno-functional and in vitro α-glucosidase, pancreatic lipase and angiotensin-converting enzyme inhibition activities.

The work was designed to assess the amelioration effect of papain hydrolysis on the biochemical, techno-functional, and biological properties of apple seed protein isolate (API) after 0-90 min of hydrolysis. Hydrolysis significantly enhanced the nutritional value (protein content ˃ 90 %) while decreasing the average particle size. With increasing hydrolysis time, FTIR analysis revealed a transition from α-helix to β-turn structure, indicating the unfolding of protein structure.

Amidative Cyclization of Alkynyl Esters to Access Pyrazin-1(2)-ones: Application to the Synthesis of Peramine and Dibromophakellin.

Herein, we report an efficient 1,5,7-Triazabicyclo[4.4.0]dec-5-ene (TBD)-catalyzed tandem intermolecular amidation and regioselective intramolecular 6--dig cyclization of alkynyl esters to efficiently access pyrazine-1(2)-one scaffolds.

Exploring the Antibacterial Potential of Semisynthetic Phytocannabinoid: Tetrahydrocannabidiol (THCBD) as a Potential Antibacterial Agent against Sensitive and Resistant Strains of .

Antimicrobial resistance (AMR) is one of the most challenging problems and is responsible for millions of deaths every year. We therefore urgently require new chemical entities with novel mechanisms of action. Phytocannabinoids have been adequately reported for the antimicrobial effect but not seriously pursued because of either stringent regulatory issues or poor drug-like properties.

A combinatorial approach of Monarda citriodora essential oil (MEO) and linalool vapors to control fruit rot of Citrus limon caused by a new pathogen, Aspergillus foetidus, and its underlying mode of action.

Aims: Citrus limon (lemon) is a widely cultivated citrus fruit. Significant postharvest losses due to fungi plague its production. Environmental and human health hazards have made the application of synthetic fungicides unsuitable.

DMSO-KOH mediated stereoselective synthesis of -enamides: an expeditious route to -enamide bearing natural products.

An efficient strategy towards stereoselective amidation of alkynes is reported. The given method features operational simplicity, excellent functional group tolerance, broad substrate scope and fast kinetics to furnish -enamides. Moreover, the method was successfully applied for the facile synthesis of the natural products lansiumamide A, lansiumamide B and -alatamide.

DNA topoisomerases as a drug target in Leishmaniasis: Structural and mechanistic insights.

Leishmaniasis, caused by a protozoan parasite, is among humanity's costliest banes, owing to the high mortality and morbidity ratio in poverty-stricken areas. To date, no vaccine is available for the complete cure of the disease. Current chemotherapy is expensive, has undesirable side effects, and faces drug resistance limitations and toxicity concerns.

Biodegradable nanocarrier of gemcitabine and tocopherol succinate synergistically ameliorates anti-proliferative response in MIA PaCa-2 cells.

Gemcitabine (GEM) is an important chemotherapeutic agent used alone or in combination with other anticancer agents for the treatment of various solid tumors. In this study, the potential of a dietary supplement, α-tocopherol succinate (TOS) was investigated in combination with GEM by utilizing human serum albumin-based nanoparticles (HSA NPs). The developed nanoparticles were characterized using DLS, SEM and FTIR and evaluated in a panel of cell lines to inspect cytotoxic efficacy.

Site-selective synthesis and pharmacological elucidation of novel semi-synthetic analogues of koenimbine as a potential anti-inflammatory agent.

Koenimbine (1), a carbazole alkaloid isolated from Murraya koenigii, belongs to the Rutaceae family. Various pharmacological effects such as anti-diabetic, melanogenesis inhibition, anti-diarrheal, anti-cancer, and anti-inflammatory properties of koenimbine have already been reported. In the current study, we investigated the anti-inflammatory role of koenimbine (1) and its novel semi-synthetic derivative 8-methoxy-3,3,5-trimethylpyrano[3,2-a] carbazole-11(3H)-yl) (3-(trifluoromethyl) phenyl) methanone (1G) in both in vitro and in vivo biological systems.