Iodine/DMSO-mediated one-pot access towards 1-aryl-2-(pyrazol-5-yl)ethane-1,2-diones via a domino reaction from functionalized pent-2-ene-1,5-diones.

A facile one-pot cascade synthesis involving simultaneous in situ pyrazole formation followed by iodine/DMSO-mediated oxidation has been established to afford 1-aryl-2-(3-aryl)-1H-pyrazol-5-yl-ethane-1,2-diones. Primarily, a two-pot approach has been established which includes the reaction of 3-methylthio-1,5-diaryl-2-pentene-1,5-diones with hydrazine in the first step to afford pyrazole, which was eventually oxidized in the next steps in the presence of iodine in DMSO. Furthermore, we performed both steps in the same pot to afford 1,2-dicarbonyl compounds in good yield. The structure of one of the compounds was confirmed by single crystal X-ray analysis. DMSO served as a solvent as well as an oxidant. Moreover, N-substituted hydrazines provided 1-(1-substituted-3-aryl-1H-pyrazol-5-yl)-2-arylethane-1,2-diones regioselectively. Furthermore, for synthetic application, 1-aryl-2-(3-aryl)-1H-pyrazol-5-yl-ethane-1,2-diones were treated with o-phenylenediamine to afford pyrazole-functionalized quinoxaline in good yield. A control reaction was carried out to understand the mechanism of product formation.

1,3-Dianionic annulation of ketones with ketene dithioacetal: a modified route to 3-aryl/cyclopropyl-5-thiomethyl-phenols and 1-(methylthio)-9,10-dihydrophenanthren-3-ols.

A simple and efficient base-mediated [3 + 3] cyclization of 1,3-dianionic ketones with 3,3-bis(methylthio)-1-arylprop-2-en-1-ones was developed to afford 3-hydroxy-biaryls, hydroxy-xylenes, and hydroxy-teraryls. Various tri- and tetra-substituted phenols were prepared from different symmetric and asymmetric ketones. The reaction of 2-(bis(methylthio)methylene)-3,4-dihydronaphthalen-1(2H)-ones with different ketones provided 1-(methylthio)-9,10-dihydrophenanthren-3-ols in very good yield. The scope of the reaction was further extended by the synthesis of cyclopropyl-functionalized phenols. One of the compounds was crystallized, and its structure was confirmed using the single-crystal X-ray approach.

Fabrication of Direct Z-Scheme CoNiWO4/Ph-gC3N4 Heterocomposites: Enhanced Photodegradation of Bisphenol A and Anticancer Activity.

Photocatalysis is realized by the design of a visible-light-active catalyst with robust redox capacity and broad absorption. In this study, a series of novel Z-scheme CoNiWO4/Ph-gC3N4 photocatalysts are synthesized to improve their redox property and photocatalytic activity toward broad visible light absorption. An intimate stable heterojunction is made between cobalt-nickel tungstate (CoNiWO4) and phenyl-doped graphitic carbon nitride (Ph-gC3N4), and its physicochemical properties are studied. The bifunctional properties of all of the synthesized materials were assessed by studying the decomposition of bisphenol A (BPA) and methyl orange (MO) dye as model pollutants, followed by an evaluation of their anticancer activity on human lung cancer cell lines. The photocatalyst with 20 wt % CoNiWO4 heterocomposite showed an enhanced response toward the removal of cancerous cells. The synthesized pristine CoNiWO4 and Ph-gC3N4 exhibit well-matched band structures and, hence, make it easier to create a Z-scheme heterocomposite. This may increase the lifetime of photoinduced charge carriers with a high redox power, thereby improving their photocatalytic and anticancer activity. An extensive analysis of the mechanism demonstrates that hydroxyl radicals (•OH) and superoxide radical anions (•O2-) are responsible for the degradation of organic compounds via Z-scheme charge transfer approach. These findings point toward a new route for creating effective Co-Ni tungstate-based direct Z-scheme photocatalysts for various redox processes, particularly the mineralization of resistant organic molecules.

Synthesis, structural characterization, antioxidant, cytotoxic activities and docking studies of schiff base Cu(II) complexes.

By combining hydrazide with 2-Acetylpyridine, a hydrazone ligand (HL) was successfully created. Several copper (II) salts have been used to create three copper (II) hydrazone complexes (acetate, sulphate, and chloride). The hydrazide ligand and its copper (II) complexes (1-3) were studied via variety of analytical techniques, including elemental analysis, electronic, infrared, UV-vis Spectrum, XRD study, thermal analysis, also molar conductivity amounts. The spectrum results indicate that in all complexes, the ligand exhibits monobasic tridentate behavior. Octahedral geometries were present in all metal complexes. The Coats-Redfern equations were used to compute and describe the dynamics properties of several steps of TGA (Ea, A, ΔH*, ΔS*, and ΔG*). Calculations using the density functional theory (DFT) were done at the molecular studio software toward examine ligands agent's and its complexes' best structures. The MCF-7 in addition to HepG-2 cell lines was resistant to tumor-inducing effects of the copper (II) chelates. The in vitro antioxidant capacities of all complexes have been estimated via DPPH free radical scavenger assays. Furthermore, zones of inhibition length accustomed to test antimicrobial effect of particular complexes in vitro towards Staphylococcus aureus (Gram positive bacteria) E. coli (Gram negative bacteria). Both absorption spectra and viscosity measurements in calf thymus DNA binding have been used to study the complexes. In order to explore docking research of copper (II) chelates, the crystallographic construction of the SARS-active CoV-2's site protein (PDB ID:6XBH) was used (COVID-19) and breast cancer distorted (PDB ID: 3hb5).

A spectroscopy based prototype for the noninvasive detection of diabetes from human saliva using nanohybrids acting as nanozyme.

The recent prediction of diabetes to be a global pandemic invites a detection strategy preferably non-invasive, and bloodless to manage the disease and the associated complications. Here, we have synthesized chitosan polymer functionalized, organic-inorganic bio-compatible nano-hybrids of Mn3O4 nanoparticles, and characterized it by utilizing several optical methodologies for the structural characterization which shows the Michaelis Menten (MM) kinetics for glucose and alpha-amylase protein (well-known diabetes biomarkers). We have also studied the potentiality for the detection of alpha-amylase in human salivary secretion which is reported to be strongly correlated with uncontrolled hyperglycemia. Finally, we have developed a prototype for the measurement of glucose (LOD of 0.38 mg/dL, LOQ of 1.15 mg/dL) and HbA1c (LOD of 0.15% and LOQ of 0.45%) utilizing the basic knowledge in the study for the detection of uncontrolled hyperglycemia at the point-of-care. With the limited number of clinical trials, we have explored the potential of our work in combating the diabetic pandemic across the globe in near future.

Highly efficient and stable AgI-CdO nanocomposites for photocatalytic and antibacterial activity.

For the last several decades, semiconducting materials and nanocomposites have received a lot of interest in generating highly efficient photocatalysts to destroy organic pollutants and eradicate bacteria. This study uses a simple deposition and precipitation approach at ambient temperature to create a unique and efficient AgI-CdO heterojunction. DRS, IR, SEM, EDS, XRD, EIS, and TEM were utilized to identify the material. SEM and TEM investigation depict the completely spherical, hexagonal forms and zigzag cubes for synthesized AgI-CdO. The EDX spectra reveal the presence of Ag, I, Cd, and O elements without impurity peaks showing that the prepared samples are highly pure. The activity of the synthesized materials was tested by degrading two different chromophoric dyes and a drug derivative (paracetamol) in an aqueous suspension under visible light. In addition, the activity of the most active catalyst was compared with Degussa P25, Fenton's reagent, and under sunlight for degradation of MB and RhB under similar conditions. Photolysis of paracetamol was also looked at using HPLC to identify intermediates formed in the photo-oxidation process. In addition, antibacterial activity was also investigated with the synthesized CdO-AgI nanocomposite in vitro against human pathogenic bacterial strains and compared with that of pure materials like AgI and standard ampicillin. The results showed excellent activity with the composite material, which could be due to the higher surface areas and the interactions between AgI and CdO nanoparticles. Quenching investigations revealed O2˙- and holes are principal reactive species. A viable photocatalytic degradation mechanism for organic pollutant elimination over the AgI-CdO nanocomposite has been sketched out based on the obtained results.

Urea-functionalized organoselenium compounds as promising anti-HepG2 and apoptosis-inducing agents.

Hepatocellular carcinoma is a highly aggressive and difficult-to-treat type of cancer. Incorporating urea functionality into the backbone of organoselenium compounds is expected to develop promising chemotherapeutic leads against liver cancer. Methods: Urea-functionalized organoselenium compounds were synthesized in good yields, and their cytotoxicity was evaluated against HepG2 cells. Results: 1,1'-(Diselanediylbis(4,1-phenylene))bis(3-phenylurea) (14) exhibited efficient anti-HepG2 activity in sub-micromolar concentrations, with no toxicity to normal human skin fibroblasts. The molecular mechanisms of the diselenide-based urea 14 were evaluated using colony formation, wound healing, 3D spheroid invasion assays, cell cycle analysis and apoptosis induction. Its redox properties were also assessed by using different bioassays. Conclusion: Our study revealed promising anticancer, antimigratory and anti-invasiveness properties of 1,1'-(diselanediylbis(4,1-phenylene))bis(3-phenylurea) (14) against HepG2.

Synthesis of antimicrobial azoloazines and molecular docking for inhibiting COVID-19.

Diverse new azoloazines were synthesized from the reaction of fluorinated hydrazonoyl chlorides with heterocyclic thiones, 1,8-diaminonaphthalene, ketene aminal derivatives, and 4-amino-5-triflouromethyl-1,2,4-triazole-2-thiol. The mechanistic pathways and the structures of all synthesized derivatives were discussed and assured based on the available spectral data. The synthesized azoloazine derivatives were evaluated for their antifungal and antibacterial activities through zone of inhibition measurement. The results revealed promising antifungal activities for compounds 4, 5, 17a,b, 19, and 25 against the pathogenic fungal strains used; Aspergillus flavus and Candida albicans compared to ketoconazole. In addition, compounds 4, 5, 19, and 25 showed moderate antibacterial activities against most tested bacterial strains. Molecular docking studies of the promising compounds were carried out on leucyl-tRNA synthetase active site of Candida albicans, suggesting good binding in the active site forming stable complexes. Moreover, docking of the synthesized compounds was performed on the active site of SARS-CoV-2 3CLpro to predict their potential as a hopeful anti-COVID and to investigate their binding pattern.

Novel Pyran-Linked Phthalazinone-Pyrazole Hybrids: Synthesis, Cytotoxicity Evaluation, Molecular Modeling, and Descriptor Studies.

A series of novel pyran-linked phthalazinone-pyrazole hybrids were designed and synthesized by a facile one-pot three-component reaction employing substituted phthalazinone, 1H-pyrazole-5-carbaldehyde, and active methylene compounds. Optimization studies led to the identification of L-proline and ethanol as efficient catalyst and solvent, respectively. This was followed by evaluation of anticancer activity against solid tumor cell lines of lung and cervical carcinoma that displayed IC50 values in the range of 9.8-41.6 µM. Molecular modeling studies were performed, and crucial interactions with the target protein were identified. The drug likeliness nature of the compounds and molecular descriptors such as molecular flexibility, complexity, and shape index were also calculated to understand the potential of the synthesized molecules to act as lead-like molecule upon further detailed biological investigations as well as 3D-QSAR studies.

Step-wise and one-pot synthesis of highly substituted conjugated trienes from 2-oxobenzo[h]chromenes/2H-pyran-2-ones.

A mild and efficient route for the synthesis of conjugated trienes via nitroethane-mediated ring contraction of 2-oxobenzo[h]chromenes/2H-pyran-2-ones followed by decarboxylative rearrangement of the obtained spirobutenolides and butenolides is described. The (E)-isomer of trienes was obtained by step-wise and one-pot approaches from 2-oxobenzo[h]chromenes. Butenolides 4a-l as new substrates have been developed for the construction of trienes. The mixture of the (E)- and (Z)-isomers of spirobutenolides undergoes decarboxylative rearrangement in the presence of sodium ethoxide as a base to yield the (E)-isomer of trienes, while the (E)-isomer of butenolides reacts to give a mixture of (2E,4E)- and (2E,4Z)-isomers of trienes in an almost steady ratio of 45 : 55 or 1 : 1.2. The structure and geometry of the obtained butenolides and trienes were confirmed by single-crystal X-ray analysis.

The Recent Development of Tetrahydro-Quinoline/Isoquinoline Based Compounds as Anticancer Agents.

Tetrahydroquinoline and isoquinoline scaffolds are important class of heterocyclic compounds, which is implied for the development of new drugs and diagnostic for therapeutic function. Naturally occurring as well as synthetic tetrahydroquinolines/isoquinolines possess many different biological activities and have been testified as remarkable cytotoxic and potency in human cancer cell lines. Tetrahydroquinoline/isoquinoline based compounds displayed a key role in the development of anticancer drugs or lead molecules and acting through various mechanisms such as cell proliferation, apoptosis, DNA fragmentation, inhibition of tubulin polymerization, induced cell cycle arrest, interruption of cell migration, and modulation. The number of tetrahydroquinoline/isoquinoline derivatives has been reported as potent anticancer agents. Due to promising anticancer activities and wideranging properties of these molecules, we have compiled the literature for the synthesis and anticancer properties of various tetrahydroquinolines and isoquinolines. We have reported the synthesis of potent tetrahydroquinoline/isoquinoline molecules of the last 10 years with their anticancer properties in various cancer cell lines and stated their half-maximal inhibitory concentration (IC50). In addition, we also considered the discussion of molecular docking and structural activity relationship wherever provided to understand the possible mode of activity a target involved and structural feature responsible for the better activity, so the reader can directly find the detail for designing new anticancer agents.

Spectral, Molecular Modeling, and Biological Activity Studies on New Schiff's Base of Acenaphthaquinone Transition Metal Complexes.

The newly synthesized Schiff's base derivative, N-allyl-2-(2-oxoacenaphthylen-1(2H)-ylidene)hydrazine-1-carbothioamide, has been characterized by different spectral techniques. Its reaction with Co(II), Ni(II), and Zn(II) acetate led to the formation of 1 : 1 (M:L) complexes. The IR and NMR spectral data revealed keto-thione form for the free ligand. On chelation with Co(II) and Ni(II), it behaved as mononegative and neutral tridentate via O, N1, and S donors, respectively, while it showed neutral bidentate mode via O and N1 atoms with Zn(II). The electronic spectra indicated that all the isolated complexes have an octahedral structure. The thermal gravimetric analyses confirmed the suggested formula and the presence of coordinated water molecules. The XRD pattern of the metal complexes showed that both Co(II) and Ni(II) have amorphous nature, while Zn(II) complex has monoclinic crystallinity with an average size of 9.10 nm. DFT modeling of the ligand and complexes supported the proposed structures. The calculated HOMO-LUMO energy gap, ΔEH-L, of the ligand complexes was 1.96-2.49 eV range where HAAT < Zn(II) < Ni(II) < Co(II). The antioxidant activity investigation showed that the ligand and Zn(II) complex have high activity than other complexes, 88.5 and 88.6%, respectively. Accordingly, the antitumor activity of isolated compounds was examined against the hepatocellular carcinoma cell line (HepG2), where both HAAT and Zn(II) complex exhibited very strong activity, IC50 6.45 ± 0.25 and 6.39 ± 0.18 µM, respectively.

Base mediated synthesis of functionalized 2-(alkynyl)arylnitriles and their molecular docking study with aromatase receptor.

A simple, efficient, and transition metal-free approach to synthesize functionalized 2-(alkynyl)benzonitriles has been developed using suitably functionalized 2H-pyran-2-ones and 4-phenyl/trimethylsilanyl-but-3-yn-2-ones as precursors. The reaction proceeds in the presence of a base at room temperature to yield internal as well as terminal alkynes. The structure of the synthesized compound was confirmed by single-crystal X-ray analysis. The molecular docking study was performed to evaluate the binding mode of action of newly synthesized alkyne derivatives with known human breast cancer target receptor aromatase (PDB ID: 3EQM).

Rational Design and Synthesis of Naphthalene Diimide Linked Bis-Naphthalimides as DNA Interactive Agents.

A molecular modeling assisted rational design and synthesis of naphthalene diimide linked bis-naphthalimides as potential DNA interactive agents is described. Chemical templates incorporating naphthalene diimide as a linker in bis-naphthalimide motif were subjected to molecular docking analysis at specific intercalation and telomeric DNA G-quadruplex sites. Excellent results were obtained, which were better than the standards. A short and convenient synthetic route was employed to access these hybrids experimentally, followed by evaluation of their ability to cause thermal denaturation of DNA and cytotoxic properties along with ADME predictions. The obtained results provided useful insights and two potential molecules were identified for further development.

Aurintricarboxylic acid and its metal ion complexes in comparative virtual screening versus Lopinavir and Hydroxychloroquine in fighting COVID-19 pandemic: Synthesis and characterization.

The salt of Aurintricarboxylic acid (ATA) was utilized in this study to synthesize new alkaline earth metal ion complexes. The analytical results proposed the isolation of mononuclear (Sr+2&Ba+2) and binuclear complexes (Mg+2&Ca+2). These complexes were analyzed by available analytical and spectral techniques. The tetrahedral geometry was suggested for all complexes (SP3) through bidentate binding mode of ligand with each central atom. UV-Vis spectra reveal the influence of L â†’ M charge transfer and the estimated optical band gap mostly appeared close to that for known semiconductors. XRD, SEM and TEM studies were executed for new complexes and reflects the nano-crystallinity and homogeneous morphology. The structural forms of ATA and its complexes were optimized by DFT/B3LYP under 6-31G and LANL2DZ basis sets. The output files (log, chk &fchk) were visualized on program screen and according to numbering scheme, many physical features were obtained. It is worthy to note that, a virtual simulation for the inhibition affinity towards COVID-19 proteins as proactive study before the actual application, was done for ATA and its complexes. This was done in addition to drugs currently applied in curing (Hydroxychloroquine & Lopinavir), for comparison and recommendation. Drug-likeness parameters were obtained to evaluate the optimal pharmacokinetics to ensure efficacy. Furthermore, simulated inhibition for COVID-19 cell-growth, was conducted by MOE-docking module. The negative allosteric binding mode represents good inhibitory behavior of ATA, Ba(II)-ATA complex and Lopinavir only. All interaction outcomes of Hydroxychloroquine drug reflect unsuitability of this drug in treating COVID-19. On the other hand, there is optimism for ATA and Lopinvir behaviors in controlling COVID-19 proliferation.

Luminescence feature of new 3,6-di(thiazolidin-5-one-2-yl)-carbazole derivative: synthesis, photophysical properties, density functional theory studies, and crystal shape effect.

A new carbazole chromophore conjugated with substituted thiazolidine-4-one (CzPT) was synthesized by applying the Knoevenagel reaction between 3,6-diformyl-N-hexylcarbazole and ethyl 2-aceto-2-(5-oxo-3-phenylthiazolidin-2-ylidene)acetate. The chemical structure of the new derivative (CzPT) was elucidated by spectral studies. The CzPT absorption spectra in different solvents exhibited a red shift for λmax by increasing solvent polarity. Bands at 430-474 nm appeared and were attributed to intramolecular charge transfer with high π-π* characteristics. CzPT fluorescence spectra exhibited a red shift after increasing the solvent polarity. To understand the Stokes' shift ( ∆ ν ¯ ) behaviour of the CzPT derivative referring to the polarity of solvents, Lippert-Mataga and linear solvation-energy relationship (LSER) models were employed in which the LSER exhibited respectable results compared with Lippert-Mataga (r2 = 0.9707). Moreover, time-dependent density functional theory absorption spectra in hexane and dimethylformamide showed that λmax had a major contribution in the highest occupied molecular orbital to lowest unoccupied molecular orbital transition in both solvents. In addition, the reduced uniformity of crystal features may lead to dislocation or anomalous arrangement of crystals with irregular spacing, which automatically enhances the optical properties of such crystals.

Colorimetric aflatoxins immunoassay by using silica nanoparticles decorated with gold nanoparticles.

Nanomaterials-based colorimetric immunoassays showed increasing attention for monitoring different biomarkers because of their unique optical and electrical features. Here, a highly sensitive and selective optical sensor was described for the determination of different aflatoxins (AFs). Mesoporous silica nanoparticles (m-SNPs) with an average particle size of 40 nm were prepared by the sol-gel method and then decorated with gold nanoparticles (AuNPs). The Au NPs@m-SiNPs nanocomposite with an average particle size of 66 nm was modified with AFs antibodies. The assay includes the following steps: the Au NPs@m-SiNPs nanocomposite was immersed with AFs antibodies, and then the AFs-Ab/Au NPs@m-SiNPs was used as a probe for AFs detection. The interaction between the AFs-Ab/Au NPs@m-SiNPs and the AFs has resulted in a change in its color from pink to violet. Measurements are performed by absorptiometry at a wavelength of 425 nm. The immunoassay works in the concentration range from 1 ng·mL-1 to 75 ng·mL-1 AFB1 and has a limit of detection 0.16 ng·mL-1 (at S/N = 3). The assay was applied to the determination of AFs in different food samples spiked with AFS. Finally, the assay was used to detect AFs in a real sample, and the LC-MS technique was used to verify the results.

Journey of anthraquinones as anticancer agents - a systematic review of recent literature.

Anthraquinones are privileged chemical scaffolds that have been used for centuries in various therapeutic applications. The anthraquinone moiety forms the core of various anticancer agents. However, the emergence of drug-resistant cancers warrants the development of new anticancer agents. The research endeavours towards new anthraquinone-based compounds are increasing rapidly in recent years. They are used as a core chemical template to achieve structural modifications, resulting in the development of new anthraquinone-based compounds as promising anticancer agents. Mechanistically, most of the anthraquinone-based compounds inhibit cancer progression by targeting essential cellular proteins. Herein, we review new anthraquinone analogues that have been developed in recent years as anticancer agents. This includes a systematic review of the recent literature (2005-2021) on anthraquinone-based compounds in cell-based models and key target proteins such as kinases, topoisomerases, telomerases, matrix metalloproteinases and G-quadruplexes involved in the viability of cancer cells. In addition to this, the developments in PEG-based delivery of anthraquinones and the toxicity aspects of anthraquinone derivatives are also discussed. The review dispenses a compact background knowledge to understanding anthraquinones for future research on the expansion of anticancer therapeutics.

Synthesis of lactobionic acid based bola-amphiphiles and its application as nano-carrier for curcumin delivery to cancer cell cultures in-vitro.

Curcumin is highly effective against various types of cancers; however, its low aqueous solubility, high metabolism and non-specificity hinder its efficacy. This study reports the synthesis of three lactobionic acid containing bola-amphiphiles and their investigation for curcumin nano-vesicular delivery into cancer cells. Synthesized bola-amphiphiles were capable of forming nano-vesicles and curcumin loading in a lipophilicity dependent manner. Bola-amphiphile with higher lipophilicity (C12) caused 89.55 ± 5.52% drug encapsulation in its spherical shape nano-vesicles (195.90 ± 0.83 nm). Bola-amphiphile resulting increased curcumin encapsulation with minimum vesicles size was further investigated for cellular uptake and in-vitro anticancer activity. Anticancer activity of curcumin significantly increased against the tested cancer cells upon loading in bola-amphiphile nano-vesicles. Furthermore, nano-vesicular drug delivery of curcumin enhanced its cellular uptake even at the lowest concentration of 1.25 µg/mL.It is concluded that the synthesized bola-amphiphile based nano-vesicles can efficiently deliver curcumin to the tested cancer cells and needs to be tested for established anticancer drugs against different cancer cell lines for effective treatment of cancer.

Transition metal-free synthesis of sterically hindered allylarenes from 5-hexene-2-one.

A simple, efficient and transition metal-free strategy was established for the synthesis of highly functionalized, sterically hindered allylarenes (6, 7 & 8) by base-mediated ring transformation of 2-oxo-6-aryl-4-(methylthio/sec-amino)-2H-pyran-3-carbonitriles (3/4) with 5-hexene-2-one (5). This provides a method for the synthesis of allylarenes functionalized with different electron donating and withdrawing groups in one pot. The structures of isolated products 6c and 7a were ascertained by spectroscopic and single crystal X-ray diffraction analyses. In addition, we have performed a molecular docking study to predict the biological activity of the synthesized molecules for binding to estrogen receptor alpha (ERα) and estrogen receptor beta (ERß).