Advancing drug discovery: Thiadiazole derivatives as multifaceted agents in medicinal chemistry and pharmacology.

In this dispensation of rapid scientific and technological advancements, significant efforts are being made to curb health-related diseases. Research discoveries have highlighted the value of heterocyclic compounds, particularly thiadiazole derivatives, due to their diverse pharmacological activities. These compounds play a crucial role in therapeutic medicine and the development of effective drugs.

Pooled multicolour tagging for visualizing subcellular protein dynamics.

Imaging-based methods are widely used for studying the subcellular localization of proteins in living cells. While routine for individual proteins, global monitoring of protein dynamics following perturbation typically relies on arrayed panels of fluorescently tagged cell lines, limiting throughput and scalability. Here, we describe a strategy that combines high-throughput microscopy, computer vision and machine learning to detect perturbation-induced changes in multicolour tagged visual proteomics cell (vpCell) pools.

Discovery of Molecular Glue Degraders via Isogenic Morphological Profiling.

Molecular glue degraders (MGDs) are small molecules that degrade proteins of interest via the ubiquitin-proteasome system. While MGDs were historically discovered serendipitously, approaches for MGD discovery now include cell-viability-based drug screens or data mining of public transcriptomics and drug response datasets. These approaches, however, have target spaces restricted to the essential proteins.

Base-mediated homologative rearrangement of nitrogen-oxygen bonds of -methyl--oxyamides.

Due to the well known reactivity of C(O)-N functionalities towards canonical C1-homologating agents ( carbenoids, diazomethane, ylides), resulting in the extrusion of the -centered fragment to carbonyl compounds, formal C1-insertions within N-O bonds still remain obscure. Herein, we document the homologative transformation of -methyl--oxyamides - with high tolerance for diverse -substituents - into -acyl-,-acetals. Under controlled basic conditions, the -methyl group of the same starting materials acts as a competent precursor of the methylene synthon required for the homologation.

Design, synthesis and anticancer activity of N-aryl indolylsulfoximines: Identification of potent and selective anticancer agents.

A facile and efficient approach utilizing copper-mediated cross-coupling reaction of N-boc-3-indolylsulfoximines with aryl iodides was developed to synthesize a diverse range of N-arylated indolylsulfoximines 11a-m in excellent yields (up to 91%). The key precursors, free NH sulfoximines 9 were readily prepared by the treatment of N-boc-3-methylthioindoles 8 with a combination of IBD and ammonium carbamate. Under similar conditions NH-free indolylsulfoximine 9a was successfully prepared in gram-scale quantities.

Highly chemoselective homologative assembly of the α-substituted methylsulfinamide motif from -sulfinylamines.

α-Substituted methylsulfinamide are prepared through the homologation of electrophilic -sulfinylamines with Li-CHXY reagents. The transformation takes place under full chemocontrol and exhibits good flexibility for preparing both -aryl and -alkyl analogues. Various sensitive functionalities can be accommodated on the starting materials, thus documenting a wide reaction scope.

Pharmacological perturbation of the phase-separating protein SMNDC1.

SMNDC1 is a Tudor domain protein that recognizes di-methylated arginines and controls gene expression as an essential splicing factor. Here, we study the specific contributions of the SMNDC1 Tudor domain to protein-protein interactions, subcellular localization, and molecular function. To perturb the protein function in cells, we develop small molecule inhibitors targeting the dimethylarginine binding pocket of the SMNDC1 Tudor domain.

Consecutive and Selective Double Methylene Insertion of Lithium Carbenoids to Isothiocyanates: A Direct Assembly of Four-Membered Sulfur-Containing Cycles.

A formal CH -CH homologation conducted with C1 carbenoids on a carbon electrophile for the obtainment of a four-membered cycle is reported. The logic proposes the consecutive delivery of two single nucleophilic CH units to an isothiocyanate-as competent electrophilic partner-resulting in the assembling of a rare imino-thietane cluster. The single synthetic operation procedure documents genuine chemocontrol, as indicated by the tolerance to various reactive elements decorating the starting materials.

Deciphering the Behavioral Response of and Toward Mustard Essential Oil.

Environmental concerns related to synthetic pesticides and the emphasis on the adoption of an integrated pest management concept as a cardinal principle have strengthened the focus of global research and development on botanical pesticides. A scientific understanding of the mode of action of biomolecules over a range of pests is key to the successful development of biopesticides. The present investigation focuses on the protein-ligand interactions of allyl isothiocyanate (AITC), a major constituent of black mustard ( essential oil (MEO) against two pests, namely, (Mi) and f.

Targeting Stress Response Pathways with Alternative Strategies as a Novel Antifungal Approach.

Fungi are recognized as key pathogens in immunocompromised patients. The invasive infection always remains a problem for clinicians due to high morbidity and mortality. The treatments of fungal infections are hampered by conventional drugs, which are associated with resistance.

Indolyl-α-keto-1,3,4-oxadiazoles: Synthesis, anti-cell proliferation activity, and inhibition of tubulin polymerization.

A series of novel indolyl-α-keto-1,3,4-oxadiazole derivatives have been synthesized by employing molecular iodine-mediated oxidative cyclization of acylhydrazones. In vitro anti cell proliferation activity of these derivatives against various cancer cells lines such as human lymphoblast (U937), leukemia (Jurkat & SB) and human breast (BT474) was investigated. Among the synthesized indolyl-α-keto-1,3,4-oxadiazoles 19a-p, only one compound (19e) exhibited significant antiproliferative activity against a panel of cell lines.

A Comprehensive and Analysis of Nematicidal Action of Essential Oils.

Nematicidal potential of essential oils (EOs) has been widely reported. Terpenoids present in most of the essential oils have been reported responsible for their bioactivity though very less is known about their modes of action. In the present study, an screening of nine Eos, namely, (OEO), (MTEO), (CEO), (TEO), (AEO), (MREO), (CNEO), (WEO), and (PEO) against revealed OEO, CNEO, and TEO as most effective with LC 39.

Chemoselective Cu-catalyzed synthesis of diverse -arylindole carboxamides, β-oxo amides and -arylindole-3-carbonitriles using diaryliodonium salts.

Chemoselective copper-catalyzed synthesis of diverse N-arylindole-3-carboxamides, β-oxo amides and N-arylindole-3-carbonitriles from readily accessible indole-3-carbonitriles, α-cyano ketones and diaryliodonium salts has been developed. Diverse N-arylindole-3-carboxamides and β-oxo amides were successfully achieved in high yields under copper-catalyzed neutral reaction conditions, and the addition of an organic base (DIPEA) resulted in a completely different selectivity pattern to produce N-arylindole-3-carbonitriles. Moreover, the importance of the developed methodology was realized by the synthesis of indoloquinolones and N-((1H-indol-3-yl)methyl)aniline and by a single-step gram-scale synthesis of the naturally occurring cephalandole A analogue.

Direct and Chemoselective Electrophilic Monofluoromethylation of Heteroatoms (-, , -, -, -) with Fluoroiodomethane.

The commercially available fluoroiodomethane represents a valuable and effective electrophilic source for transferring the CHF unit to a series of heteroatom-centered nucleophiles under mild basic conditions. The excellent manipulability offered by its liquid physical state (bp 53.4 °C) enables practical and straightforward one-step nucleophilic substitutions to retain the chiral information embodied, thus allowing it to overcome the requirement for fluoromethylating agents with no immediate access.

Downconversion Luminescence-Based Nanosensor for Label-Free Detection of Explosives.

We report a selective and sensitive nanosensor probe based on polyethylenimine (PEI)-capped downconverting nanophosphors β-NaYF:Gd,Tb@PEI for the detection of 2,4,6-trinitrotoluene (TNT), both in water and buffer media. These downconverting phosphors were synthesized via a hydrothermal route and are known to show excellent chemical, thermal, and photostability. They emit sharp emission peaks centered at ∼488, 544, 584, and 619 nm, among which the peak at ∼544 nm was remarkably quenched (∼90%) by the addition of TNT without giving any new emission peak.

Graphene Quantum Dots-Driven Multiform Morphologies of β-NaYF:Gd/Tb Phosphors: The Underlying Mechanism and Their Optical Properties.

Dimension and shape tunable architectures of inorganic crystals are of extreme interest because of morphology-dependent modulation of the properties of the materials. Herein, for the first time, we present a novel impurity-driven strategy where we studied the influence of in situ incorporation of graphene quantum dots (GQDs) on the growth of β-NaYF:Gd/Tb phosphor crystals via a hydrothermal route. The GQDs function as a nucleation site and by changing the concentration of GQDs, the morphology of β-NaYF:Gd/Tb phosphors was changed from rod to flowerlike structure to disklike structure, without phase transformation.