Design, Synthesis, and Characterization of Polyoxotungstate-Decorated Ionic Liquid-Based Hybrid Material, [BmIm]4[SiW12O40] toward Rapid Adsorption of Dye and Antibacterial Activities.

A multifunctional polyoxometalate-ionic liquid (POM-IL)-based hybrid material comprising silicotungstic acid, [BmIm]4[SiW12O40], has been synthesized and demonstrated its efficiency toward methylene blue removal and as an antibacterial agent. Single-crystal XRD analysis confirms that the material crystallizes in monoclinic symmetry (SG: Pn), with lattice parameters a = 13.1396(5) Å, b = 16.9655(8) Å, c = 14.3493(7) Å, and Z = 2. The structure comprises a single polyanionic [SiW12O40]4- moiety surrounded by four cationic [BmIm]+ units of two different conformations, which supported DFT and Hirshfeld surface analysis. The material shows excellent removal efficiency for methylene blue, with a maximum adsorption capacity of 92.47 mg/g and 83.05% reusability after five cycles. On the contrary, FTIR and ζ-potential analyses confirm that electrostatic interactions are the predominant factors governing the adsorption process. The material also acts as a superior antibacterial agent against the opportunistic pathogens Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli with a MIC of 500-700 µg/mL. However, a comparative assessment showed that the material was more effective against P. aeruginosa compared to the other two pathogens. PXRD analysis confirms the phase purity, and FESEM and TEM analyses exhibit block-shaped morphology with particle sizes ∼2-3 µm.

EpCAM-targeted betulinic acid analogue nanotherapy improves therapeutic efficacy and induces anti-tumorigenic immune response in colorectal cancer tumor microenvironment.

BACKGROUND: Betulinic acid (BA) has been well investigated for its antiproliferative and mitochondrial pathway-mediated apoptosis-inducing effects on various cancers. However, its poor solubility and off-target activity have limited its utility in clinical trials. Additionally, the immune modulatory role of betulinic acid analogue in the tumor microenvironment (TME) is largely unknown. Here, we designed a potential nanotherapy for colorectal cancer (CRC) with a lead betulinic acid analogue, named as 2c, carrying a 1,2,3-triazole-moiety attached to BA through a linker, found more effective than BA for inhibiting CRC cell lines, and was chosen here for this investigation. Epithelial cell adhesion molecule (EpCAM) is highly overexpressed on the CRC cell membrane. A single-stranded short oligonucleotide sequence, aptamer (Apt), that folds into a 3D-defined architecture can be used as a targeting ligand for its specific binding to a target protein. EpCAM targeting aptamer was designed for site-specific homing of aptamer-conjugated-2c-loaded nanoparticles (Apt-2cNP) at the CRC tumor site to enhance therapeutic potential and reduce off-target toxicity in normal cells. We investigated the in vitro and in vivo therapeutic efficacy and anti-tumorigenic immune response of aptamer conjugated nanotherapy in CRC-TME. METHODS: After the characterization of nanoengineered aptamer conjugated betulinic acid nanotherapy, we evaluated therapeutic efficacy, tumor targeting efficiency, and anti-tumorigenic immune response using cell-based assays and mouse and rat models. RESULTS: We found that Apt-2cNP improved drug bioavailability, enhanced its biological half-life, improved antiproliferative activity, and minimized off-target cytotoxicity. Importantly, in an in vivo TME, Apt-2cNP showed promising signs of anti-tumorigenic immune response (increased mDC/pDC ratio, enhanced M1 macrophage population, and CD8 T-cells). Furthermore, in vivo upregulation of pro-apoptotic while downregulation of anti-apoptotic genes and significant healing efficacy on cancer tissue histopathology suggest that Apt-2cNP had predominantly greater therapeutic potential than the non-aptamer-conjugated nanoparticles and free drug. Moreover, we observed greater tumor accumulation of the radiolabeled Apt-2cNP by live imaging in the CRC rat model. CONCLUSIONS: Enhanced therapeutic efficacy and robust anti-tumorigenic immune response of Apt-2cNP in the CRC-TME are promising indicators of its potential as a prospective therapeutic agent for managing CRC. However, further studies are warranted.

Crystal to Hydrogel Transformation in S-Benzyl-L-Cysteine-Containing Cyclic Dipeptides - Nanostructure Elucidation and Applications.

Cyclic dipeptides (CDPs) are crucial building blocks for a range of functional nanomaterials due to their simple chemical structure and high molecular stability. In this investigation, we synthesized a set of S-benzyl-L-cysteine-based CDPs (designated as P1-P6) and thoroughly examined their self-assembly behavior in a methanol-water solvent to elucidate the relationship between their structure and gelation properties. The hydrophobicity of the amino acids within the CDPs was gradually increased. The present study employed a comprehensive array of analytical techniques, including NMR, FT-IR, AFM, thioflavin-T, congo-red CD, X-ray crystallography, and biophysical calculations like Hirshfield Surface analysis and DFT analysis. These methods revealed that in addition to hydrogen bonding, the hydrophobic nature of the amino acid side chain significantly influences the propensity of CDPs to form hydrogels. Each CDP yielded distinct nanofibrillar networks rich in ß-sheet structures, showcasing unique morphological features. Moreover, we explored the practical application of these CDP-based hydrogels in water purification by utilizing them to remove harmful organic dyes from contaminated water. This application underscores the potential of CDPs in addressing environmental challenges, offering a promising avenue for the future development of these materials in water treatment technologies.

Solvent Geometry Regulated J- and H-Type Aggregates of Photoswitchable Organogelator: Phase-Selective Thixotropic Gelation and Oil Spill Recovery.

We demonstrate supramolecular polymerization and formation of 1D nanofiber of azobenzene based organogelator (AZO-4) in cyclic hydrocarbon solvents (toluene and methylcyclohexane). The AZO-4 exhibits J- and H-type aggregates in toluene: MCH (9 : 1) and MCH: toluene (9 : 1) respectively. The type of aggregate was governed by the geometry of the solvents used in the self-assembly process. The J-type aggregates with high thermal stability in toluene is due to the enhanced interaction of AZO-4 π- surface with the toluene π-surface, whereas H-aggregate with moderate thermal stability in MCH was due to the interruption of the cyclic hydrocarbon in van der Waals interactions of peripheral chains of AZO-4 molecule. The light induced reversible photoisomerization is observed for both J- and H-aggregates. The macroscopic property revealed spontaneous and strong gelation in toluene preferably due to the strong interactions of the AZO-4 nanofibers with the toluene solvent molecules compared to the MCH. The rheological measurements revealed thixotropic nature of the gels by step-strain experiments at room temperature. The thermodynamic parameter (ΔHm) of gel-to-sol transition was determined for all the gels to get more insight into the gelation property. Furthermore, the phase selective gelation property was extended to the oil spill recovery application using diesel/water and petrol/water mixture.

Comparative study on Antibacterial efficacy of a series of chromone sulfonamide derivatives against drug-resistant and MDR-isolates.

Sulfonamide derivatives have numerous pharmaceutical applications having antiviral, antibacterial, antifungal, antimalarial, anticancer, and antidepressant activities. The structural flexibility of sulfonamide derivatives makes them an excellent candidate for the development of new multi-target agents, although long-time exposure to sulfonamide drugs results in many toxic impacts on human health. However, sulfonamides may be functionalized for developing less toxic and more competent drugs. In this work, sulfonamides including Sulfapyridine (a), Sulfathiazole (b), Sulfamethoxazole (c), and Sulfamerazine (d) are used to synthesize Schiff bases of 7-hydroxy-4-methyl-2-oxo-2H-chromene-8-carbalde-hyde (1a-1d). The synthesized compounds were spectroscopically characterized and tested against hospital isolates of three Gram-positive (Methicillin-resistant Staphylococcus aureus PH217, Ampicillin-resistant Coagulase-negative Staphylococcus aureus, multidrug-resistant (MDR) Enterococcus faecalis PH007R) and two Gram-negative bacteria (multidrug-resistant Escherichia coli, and Salmonella enterica serovar Typhi), compared to the quality control strains from ATCC (S. aureus 29213, E. faecalis 25922, E. coli 29212) and MTCC (S. Typhi 734). Two of the four Schiff bases 1a and 1b are found to be more active than their counterpart 1c and 1d; while 1a have showed significant activity by inhibiting MRSA PH217 and MDR isolates of E. coli at the minimum inhibitory concentration (MIC) of 150 µg/mL and 128 µg/mL with MBC of 1024 µg/mL, respectively. On the other hand, the MIC of 1b was 150 µg/mL against both S. aureus ATCC 29213 and Salmonella Typhi MTCC 734, compared to the control antibiotics Ampicillin and Gentamycin. Scanning electron microscopy demonstrated the altered surface structure of bacterial cells as a possible mechanism of action, supported by the in-silico molecular docking analysis.

Entropy-Enthalpy Compensation in Solvent Geometry Regulated Supramolecular Polymerization of Luminescent Napthalimide via a Non-Cooperative, Isodesmic Mechanism.

Supramolecular polymers of π-conjugated systems are an important class of materials with fascinating functions and properties originated from the dynamic behavior and highly ordered molecular organizations. Here, a donor-π-acceptor based functionalized luminescent napthalene monoimide (NMI) undergoes J-type self-assembly by non-covalent interactions via a non-cooperative, isodesmic mechanism to form supramolecular 1D nanowire. The fundamental insights into the thermodynamics regulating the supramolecular polymerization were derived through the fitting of the isodesmic model to variable temperature UV/Vis data in linear (dodecane) and nonliner hydrocarbon (decalin) based solvents. This shows a significant role of entropy-enthalpy compensation in solvent geometry-regulated formation and stabilization of supramolecular polymer. Furthermore, we have quantitively estimated the influence of solvent geometry and found that NMI forms stronger self-assembly and spontaneous gel in linear hydrocarbon based solvent compared to nonliner one and thereby substantially increases the degree of polymerization in linear hydrocarbon solvent (dodecane). This is accredited to the effective influence of the linear hydrocarbon solvent molecules in the polymerization process by favourable van der waals interactions with the peripheral alkyl chains of the NMI monomers in contrast to unfavourable interaction of nonliner hydrocarbon solvent due to geometry mismatch.

Urea-Promoted Neat Synthesis of Fused Dihydroisoquinolines and Disubstituted Pyridines: A Mechanistic Observation with Molecular-Sensing Studies.

An efficient and short synthesis of fused dihydroisoquinolines, diaryl substituted pyridine derivatives in good to high yields has been established by using an environmentally safe, solvent-metal-oxidant-free tandem approach. In this article, we discuss how the electrocyclic reaction is more pronounced in the solid phase in the presence of urea, whereas the typical aza-Michael addition is more prominent in presence of arylamine in the solution phase for 3-(2-formylcycloalkenyl)acrylic ester derivative substrates. The wide range of substrates and urea-promoted neat synthesis made our approach more significant in medical and also analytical science. Moreover, an isoquinoline alkaloid decumbenine B analogue has been synthesized by using our newly developed neat methodology. We have also investigated the photophysical properties of the synthesized fused dihydroisoquinoline derivatives. One of the synthesized molecules was used as a sensor for the selective detection of toxic picric acid. Therefore, the effective neat synthesis and molecular sensing applications of these compounds made our approach more exciting in the field of heterocyclic chemistry.

A novel nickel(II) complex with N,S donor Schiff base: Structural characterisation, DFT, TD-DFT study and catalytic investigation.

One new mononuclear nickel(II) thiosemicarbazone complex (1), has been synthesised from the Schiff base ligand derived from p-anisaldehyde and thiosemicarbazide. Complex 1 is characterized by using different spectroscopic techniques and single crystal X-ray structure analysis. Time dependent density functional theory (TD-DFT) was performed to simulate the electronic spectra of the complex 1 with the help of Polarizable Continuum Model (PCM) model. Complex 1 acts as functional models. The catalytic property has been evaluated from Lineweaver-Burk plot using the Michaelis-Menten approach of enzyme catalysis with a kcat value of the order of 708 h-1.

Structural modulation of insulin by hydrophobic and hydrophilic molecules.

In the bloodstream, insulin interacts with various kinds of molecules, which can alter its structure and modulate its function. In this work, we have synthesized two molecules having extremely hydrophilic and hydrophobic side chains. The effects of hydrophilic and hydrophobic molecules on the binding with insulin have been investigated through a multi-spectroscopic approach. We found that hydrophilic molecules have a slightly higher binding affinity towards insulin. Insulin can bind with the hydrophilic molecules as it binds glucose. The high insulin binding affinity of a hydrophobic molecule indicates its dual nature. The hydrophobic molecule binds at the hydrophobic pocket of the insulin surface, where hydrophilic molecules interact at the polar surface of the insulin. Such binding with the hydrophobic molecule perturbs strongly the secondary structure of the insulin much more in comparison to hydrophilic molecules. Therefore, the stability of insulin decreases in the presence of hydrophobic molecules.

Anion-assisted supramolecular polymerization of luminescent organic π-conjugated chromophores in a moderately polar solvent: tunable nanostructures and their corresponding effects on electronic properties.

Supramolecular polymers of π-conjugated organic chromophores have emerged as promising candidates in organic electronics because of their dynamic and highly ordered molecular organization. Herein, we demonstrate the formation of luminescent, highly conducting supramolecular polymers of a functionalized naphthalimide π-chromophore-based organic semiconductor in a moderately polar organic solvent (tetrahydrofuran) by overcoming solute-solvent H-bonding via assistance from fluoride anions. The polymerization is exclusively guided by the synergistic effects of cascade H-bonding (F-⋯H-N- of primary amines, followed by -CO⋯H-N- of amides), π-π stacking and hydrophobic interactions. An increasing molar equivalent of anions leads to a morphology transition from 1D nanowires to 2D nanosheets via nanotubes and nanorings, but above a particular threshold of the same anion, depolymerization-mediated disruption of long-range order and formation of non-luminescent spherical particles was observed. Such significant impacts of anions in supramolecular polymerization-depolymerization were utilized in modulating the electronic properties of this naphthalimide-based organic semiconductor.

Small Molecule Interactions with Biomacromolecules: DNA Binding Interactions of a Manganese(III) Schiff Base Complex with Potential Anticancer Activities.

A manganese(III) complex, [MnIII(L)(SCN)(enH)](NO3)·H2O (1•H2O) (H2L = 2-((E)-(2-((E)-2-hydroxy-3-methoxybenzylidene-amino)-ethyl-imino)methyl)-6-methoxyphenol), has been synthesized and characterized by single-crystal X-ray diffraction analysis. The interaction of 1•H2O with DNA was studied by monitoring the decrease in absorbance of the complex at λ = 324 nm with the increase in DNA concentration, providing an opportunity to determine the binding constant of the 1•H2O-ct-DNA complex as 5.63 × 103 M-1. Similarly, fluorescence titration was carried out by adding ct-DNA gradually and monitoring the increase in emission intensity at 453 nm on excitation at λex = 324 nm. A linear form of the Benesi-Hildebrand equation yields a binding constant of 4.40 × 103 M-1 at 25 °C, establishing the self-consistency of our results obtained from absorption and fluorescence titrations. The competitive displacement reactions of dyes like ethidium bromide, Hoechst, and DAPI (4',6-diamidine-2'-phenylindole dihydrochloride) from dye-ct-DNA conjugates by 1•H2O were analyzed, and the corresponding KSV values are 1.05 × 104, 1.25 × 104, and 1.35 × 104 M-1 and the Kapp values are 2.16 × 103, 8.34 × 103, and 9.0 × 103 M-1, from which it is difficult to infer the preference of groove binding over intercalation by these DNA trackers. However, the molecular docking experiments and viscosity measurement clearly indicate the preference for minor groove binding over intercalation, involving a change in Gibbs free energy of -8.56 kcal/mol. The 1•H2O complex was then evaluated for its anticancer potential in breast cancer MCF-7 cells, which severely abrogates the growth of the cells in both 2D and 3D mammospheres, indicating its promising application as an anticancer drug through a minor groove binding interaction with ct-DNA.

Anti-HSV nucleoside and non-nucleoside analogues: spectroscopic characterisation of naphthyl and coumarinyl amides and their mode and mechanism of antiviral action.

Nucleoside analogues acyclovir, valaciclovir, and famciclovir are the preferred drugs against human Herpes Simplex Viruses (HSVs). However, the viruses rapidly develop resistance against these analogues which demand safer, more efficient, and nontoxic antiviral agents. We have synthesized two non-nucleoside amide analogues, 2-Oxo-2H-chromene-3-carboxylic acid [2-(pyridin-2-yl methoxy)-phenyl]-amide (HL1) and 2-hydroxy-1-naphthaldehyde-(4-pyridine carboxylic) hydrazone (HL2). The compounds were characterized by different physiochemical methods including elementary analysis, FT-IR, Mass spectra, 1H-NMR; and evaluated for their antiviral efficacy against HSV-1F by Plaque reduction assay. The 50% cytotoxicity (CC50), determined by MTT test, revealed that HL1 (270.4 µg/ml) and HL2 (362.6 µg/ml) are safer, while their antiviral activity (EC50) against HSV-1F was 37.20 µg/ml and 63.4 µg/ml against HL1 and HL2 respectively, compared to the standard antiviral drug Acyclovir (CC50 128.8 ± 3.4; EC50 2.8 ± 0.1). The Selectivity Index (SI) of these two compounds are also promising (4.3 for HL1 and 9.7 for HL2), compared to Acyclovir (49.3). Further study showed that these amide derivatives block the early stage of the HSV-1F life cycle. Additionally, both these amides make the virus inactive, and reduce the number of plaques, when infected Vero cells were exposed to HL1 and HL2 for a short period of time. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03658-0.

Live-Cell Mitochondrial Targeted NIR Fluorescent Covalent Labeling of Specific Proteins Using a Dual Localization Effect.

Here, our designed water-soluble NIR fluorescent unsymmetrical Cy-5-Mal/TPP+ consists of a lipophilic cationic TPP+ subunit that can selectively target and accumulate in a live-cell inner mitochondrial matrix where a maleimide residue of the probe undergoes faster chemoselective and site-specific covalent attachment with the exposed Cys residue of mitochondrion-specific proteins. On the basis of this dual localization effect, Cy-5-Mal/TPP+ molecules remain for a longer time period even after membrane depolarization, enabling long-term live-cell mitochondrial imaging. Due to the adequate concentration of Cy-5-Mal/TPP+ reached in live-cell mitochondria, it facilitates site-selective NIR fluorescent covalent labeling with Cys-exposed proteins, which are identified by the in-gel fluorescence assay and LC-MS/MS-based proteomics and supported by a computational method. This dual targeting approach with admirable photostability, narrow NIR absorption/emission bands, bright emission, long fluorescence lifetime, and insignificant cytotoxicity has been shown to improve real-time live-cell mitochondrial tracking including dynamics and interorganelle crosstalk with multicolor imaging applications.

Synthesis of Multifused Pyrrolo[1,2-a]quinoline Systems by Tandem Aza-Michael-Aldol Reactions and Their Application to Molecular Sensing Studies.

Herein, we have presented a weak acid-promoted tandem aza-Michael-aldol strategy for the synthesis of diversely fused pyrrolo[1,2-a]quinoline (tricyclic to pentacyclic scaffolds) by the construction of both pyrrole and quinoline ring in one pot. The described protocol fabricated two C-N bonds and one C-C bond in the pyrrole-quinoline rings which have been sequentially formed under transition-metal-free conditions by the extrusion of eco-friendly water molecules. A ketorolac drug analogue has been synthesized following the current protocol, and one of the synthesized tricyclic pyrrolo[1,2-a]quinoline fluorophores has been used to detect highly toxic picric acid via the fluorescence quenching effect.

Arylative Methylation of 2,3-Dihydropyrazines and Pyrazinones Using Dimethyl Sulfoxide as a C1 Source.

Divergent synthesis of α-C-H methylated pyrazines and pyrazinones using dimethyl sulfoxide as a nonconventional methylating agent under metal-free conditions was reported. Dimethyl sulfoxide-coordinated bromine cation pools generated from the treatment of dimethyl sulfoxide and 1,2-dibromoethane undergo Pummerer-type fragmentation to afford an electrophilic methyl(methylene)sulfonium ion for reaction with a carbon nucleophile followed by aromatization to afford α-methylated pyrazines and pyrazinones.

Evaluation of F-18 FDG radiopharmaceuticals through Molecular Docking and radiation effects.

Fluorodeoxyglucose (FDG), marked with the most used Positron Emission Tomography (PET) radiopharmaceutical Fluorine-18 (F-18), is a glucose analog and is taken to living cells through membrane glucose carriers. F-18 FDG involvement in tissue is proportional to glucose use. In many cancers, there is increased glucose use due to increased gluten expression and hexokinase activity. F-18 FDG PET is a proven method for diagnosis, staging, re-staging, and evaluation of treatment response in oncology. The purpose of this study is to find the effect of ionizing radiation on proteins in the mechanism of action of FDG and determine to Molecular mechanisms of F-18 FDG accumulation in metabolism. In the study, two different models were used together, the first method, the study was Molecular Docking method for modeling molecules deconstructed and the structure of FDG was energy minimized by utilizing the density functional theory, and the B3LYP functional was used with 6-311G basis set. The second method was the Monte Carlo method for modeling ionizing radiation interactive with the potential routes of FDG metabolism within the cell. It was determined that the Gibbs free energy (ΔG) change was compatible with the ionizing radiation factors for binding of FDG to the aphthous regions of Glucose-6-phosphate isomerase (G1), hexokinase (G2), and glucose transporter-1 (G3) were selected. In this study, the strong binding of FDG to protein influences the effect of radiation on the active site of enzymes. The G1 and G3 shown in the study interacted with only one charged amino acid FDG, and the absence of an aromatic residue around it can be considered among the results of this study as the cause of the low protective effect against ionizing radiation.

Structural, Theoretical Investigations, Hirshfeld Surface Analysis, and Cytotoxicity Profile of a Neocuproine-Co(II)-Based Discrete Homodinuclear Complex.

In this work, we aimed to synthesize a new cobalt(II) complex, namely [Co2(µ-HIPA)(NC)2(H2O)3(NO3)]·(NO3)(C2H5OH)(1) (where H3IPA = 5-hydroxy isophthalic acid and NC = 2,9-dimethyl-1,10-phenanthroline or neocuproine), as a promising chemotherapeutic agent. The diffraction (single crystal-XRD and powder-XRD), spectroscopic (FTIR and UV-visible), molar conductance, and thermal techniques were used to characterize complex 1. Single-crystal X-ray diffraction analysis reveals that Co(II) exists in an octahedral geometry, with the ligation of four oxygen atoms, and two nitrogen atoms. Topological analysis of complex 1 reveals 2,6C6 topological type as an underlying net. The plausible intermolecular interactions within complex 1 that control the crystal packing were analyzed by Hirshfeld surface analysis. In vitro cytotoxicity of complex 1 was evaluated against acute myeloid leukemia (THP-1), colorectal (SW480), and prostate (PC-3) cancer cell lines by utilizing an MTT assay. The result shows that complex 1 can inhibit the growth of cancer cells (THP-1, SW480, and PC-3) at lower inhibitory concentration (IC50) values of > 100, 43.6, and 95.1 µM respectively. The morphological changes induced by complex 1 on THP-1 and SW480 cancer cell lines were carried out with acridine orange/ethidium bromide staining methods. Additionally, comprehensive molecular docking studies were performed to understand the potential binding interactions of complex 1 with different bio-macromolecules.

Interaction with bioligands and in vitro cytotoxicity of a new dinuclear dioxido vanadium(V) complex.

One centrosymmetric bis(µ-oxido)-bridged vanadium(V) dimer with molecular formula [(VVO2)2(pedf)2] (1) has been synthesized from the reaction of VOSO4·5H2O with a Schiff base ligand (abbreviated with pedf-) obtained from 2-acetylpyridine and 2-furoic hydrazide in methanol. Complex 1 was characterized by elemental analysis, UV-visible (UV-Vis), Fourier-transform infrared spectra (FT-IR), cyclic voltammetry (CV), electron paramagnetic resonance spectroscopy (EPR) and electrospray ionization-mass spectrometry (ESI-MS) techniques along with single crystal X-ray diffraction (SCXRD). The FT-IR spectral data of 1 indicated the involvement of oxygen and azomethine nitrogen in coordination to the central metal ion. The crystallographic studies revealed a dinuclear oxovanadium(V) complex with the Schiff base coordinated via the ONN donor set with formation of two five-membered chelate rings resulting in a distorted octahedral geometry. The interaction of 1 with calf thymus DNA (CT-DNA) was investigated by spectroscopic measurements and results suggested that the complex binds to CT-DNA via moderate intercalative mode with a binding constant (Kb) around 103 M-1. In addition, the in vitro protein binding behavior was studied by fluorescence spectrophotometric method using both bovine serum albumin (BSA) and human serum albumin (HSA) and a static quenching mechanism was observed for the interaction of the complex with both albumins that occurs with a Kb in the range (5-6) × 103 M-1. In vitro cytotoxicity of complex 1 on lung cancer cells (A549) and human skin carcinoma cell line (A431) demonstrated that the complex had a broad-spectrum of anti-proliferative activity with IC50 value of 64.2 µM and 56.2 µM.

Identification of 4-acrylamido-N-(pyridazin-3-yl)benzamide as anti-COVID-19 compound: a DFTB, molecular docking, and molecular dynamics study.

Omicron is one of the variants of COVID-19 and continuing member of a pandemic. There are several types of vaccines that were developed around the globe to fight against the virus. However, the world is suffering to find suitable drug candidates for the virus. The main protease (Mpro) enzyme of the virus is the best target for finding drug molecules because of its involvement in viral infection and protein synthesis. ZINC-15 is a database of 750 million commercially available compounds. We find 125 compounds having two aromatic rings and amide groups for non-covalent interactions with active site amino acids and functional groups with the capability to bind -SH group of C145 of Mpro through covalent bonding by a nucleophilic addition reaction. The lead compound (Z144) was identified using molecular docking. The non-covalent interactions (NCI) calculations show the interactions between amino acids present in the active site of the protein and the lead molecules are attractive in nature. The density functional-based tight-binding (DFTB) study of the lead compound with amino acids in the active site indicates that Q190 and Q193 play a very critical role in stabilization. The Michael addition of the acrylamide group of the lead molecule at ß-position is facile because the low energy lowest unoccupied molecular orbital (LUMO) is concentrated on the group. From molecular dynamics during 100 ns, it has come to light that strong non-covalent interactions are key for the stability of the lead inside the protein and such binding can fold the protein. The free energy for this interaction is -42.72 kcal mol-1 which was obtained from MM-GB/SA calculations.

Correction: Coumarin derivatives inhibit the aggregation of ß-lactoglobulin.

[This corrects the article DOI: 10.1039/D2RA01029A.].