Simmons-Smith Cyclopropanation: A Multifaceted Synthetic Protocol toward the Synthesis of Natural Products and Drugs: A Review.

Simmons-Smith cyclopropanation is a widely used reaction in organic synthesis for stereospecific conversion of alkenes into cyclopropane. The utility of this reaction can be realized by the fact that the cyclopropane motif is a privileged synthetic intermediate and a core structural unit of many biologically active natural compounds such as terpenoids, alkaloids, nucleosides, amino acids, fatty acids, polyketides and drugs. The modified form of Simmons-Smith cyclopropanation involves the employment of Et2Zn and CH2I2 (Furukawa reagent) toward the total synthesis of a variety of structurally complex natural products that possess broad range of biological activities including anticancer, antimicrobial and antiviral activities. This review aims to provide an intriguing glimpse of the Furukawa-modified Simmons-Smith cyclopropanation, within the year range of 2005 to 2022.

Investigation of boron-doped graphene oxide anchored with copper sulphide flowers as visible light active photocatalyst for methylene blue degradation.

The non-biodegradable nature of waste emitted from the agriculture and industrial sector contaminates freshwater reserves. Fabrication of highly effective and low-cost heterogeneous photocatalysts is crucial for sustainable wastewater treatment. The present research study aims to construct a novel photocatalyst using a facile ultrasonication-assisted hydrothermal method. Metal sulphides and doped carbon support materials work well to fabricate hybrid sunlight active systems that efficiently harness green energy and are eco-friendly. Boron-doped graphene oxide-supported copper sulphide nanocomposite was synthesized hydrothermally and was assessed for sunlight-assisted photocatalytic degradation of methylene blue dye. BGO/CuS was characterized through various techniques such as SEM-EDS, XRD, XPS, FTIR, BET, PL, and UV-Vis DRS spectroscopy. The bandgap of BGO-CuS was found to be 2.51 eV as evaluated through the tauc plot method. The enhanced dye degradation was obtained at optimum conditions of pH = 8, catalyst concentration (20 mg/100 mL for BGO-CuS), oxidant dose (10 mM for BGO-CuS), and optimum time of irradiation was 60 min. The novel boron-doped nanocomposite effectively degraded methylene blue up to 95% under sunlight. Holes and hydroxyl radicals were the key reactive species. Response surface methodology was used to analyze the interaction among several interacting parameters to remove dye methylene blue effectively.

Repositioning of acefylline as anti-cancer drug: Synthesis, anticancer and computational studies of azomethines derived from acefylline tethered 4-amino-3-mercapto-1,2,4-triazole.

Novel azomethines derived from acefylline tethered triazole hybrids (7a-k) have been synthesized and evaluated against human liver cancer cell line (Hep G2) using MTT assay. The synthesized series of azomethines exhibited promising efficacy against liver cancer cell line. Screening of the synthesized series identified compound 7d with the least cell viability value (11.71 ± 0.39%) as the most potent anticancer agent in contrast to the reference drug acefylline (cell viability = 80 ± 3.87%). In this study, the potentials of the novel agents (7a-k) to inhibit liver cancer proteins were assessed. Subsequently, the structure-activity relationship of the potential drug candidates was assessed via ADME/T molecular screening. The cytotoxic potential of these derivatives was also investigated by hemolysis and thrombolysis. Their hemolytic and thrombolytic studies showed that all of these drugs had very low cytotoxicity and moderate clot lysis activity. Compound 7g (0.26% hemolysis) and 7k (52.1% clot lysis) were the least toxic and moderate thrombolytic agents respectively.

Ultrasound-Assisted Synthesis and In Silico Modeling of Methanesulfonyl-Piperazine-Based Dithiocarbamates as Potential Anticancer, Thrombolytic, and Hemolytic Structural Motifs.

Piperazine-based dithiocarbamates serve as important scaffolds for numerous pharmacologically active drugs. The current study investigates the design and synthesis of a series of dithiocarbamates with a piperazine unit as well as their biological activities. Under ultrasound conditions, the corresponding piperazine-1-carbodithioates 5a-5j were synthesized from monosubstituted piperazine 2 and N-phenylacetamides 4a-4j in the presence of sodium acetate and carbon disulfide in methanol. The structures of the newly synthesized piperazines were confirmed, and their anti-lung carcinoma effects were evaluated. A cytotoxic assay was performed to assess the hemolytic and thrombolytic potential of the synthesized piperazines 5a-5j. The types of substituents on the aryl ring were found to affect the anticancer activity of piperazines 5a-5j. Piperazines containing 2-chlorophenyl (5b; cell viability = 25.11 ± 2.49) and 2,4-dimethylphenyl (5i; cell viability = 25.31 ± 3.62) moieties demonstrated the most potent antiproliferative activity. On the other hand, piperazines containing 3,4-dichlorophenyl (5d; 0.1%) and 3,4-dimethylphenyl (5j; 0.1%) rings demonstrated the least cytotoxicity. The piperazine with the 2,5-dimethoxyphenyl moiety (5h; 60.2%) showed the best thrombolytic effect. To determine the mode of binding, in silico modeling of the most potent piperazine (i.e., 5b) was performed, and the results were in accordance with those of antiproliferation. It exhibits a similar binding affinity to PQ10 and an efficient conformational alignment with the lipophilic site of PDE10A conserved for PQ10A.

Phosphorus Fertilizers Enhance the Phytoextraction of Cadmium through Solanum nigrum L.

Cadmium (Cd) toxicity strongly influences plants growth and seed germination in crop plants. This pot trial had aimed evaluate the benefits of two different kinds of phosphorus (P)-fertilizer in the phytoremediation of Cd by Solanum nigrum L. The current pot experiment was conducted to evaluate the role of P-fertilizers in phytoremediation of Cd by Solanum nigrum L. Single superphosphate (SSP) contain 7 to 9% P and Di-ammonium Phosphate (DAP) contain 46% P had been applied in single and combine form in soil with different ratios (0:0, 100:0, 0:100, 50:50%) accompanied by diverse Cd levels (0, 25, 50 mg kg-1). Three weeks seeding were transferred into pots, and plants had been harvested afterward seventy days of growth in the pots. Significantly inhibited plant growth was observed in shoots and roots of Cd contaminated plants. Cadmium stress had stimulated oxidative stress in subjected plants. However, supplementation of P-fertilizers in an optimum manner significantly increased plant biomass along with enhancing antioxidants enzymatic activities and inhibiting oxidative stress. Maximum plant-growth had been noted in SSP + DAP supplemented plants in contrast to single SSP, DAP supplemented plants. Higher Cd concentrations observed in SSP + DAP supplemented plants over single treatment. It has been concluded that combination of SSP + DAP might be a better option to improve growth as well as uptake capacity of Solanum nigrum L. under Cd stress. However, a field study is recommended for detailed future investigations.

Effect of pH on Fluorescence Spectra of Coumarin Derivatives.

Colourless crystalline solid coumarin with a bitter taste and sweet vanilla-like odor mostly acts as chemical protection against predators in plants. Anticoagulants (blood thinners), anti-fungicidal, anti-tumor and anti-inflammatory properties of coumarin are all used to treat skin diseases. Because of internal charge transfer (ICT), coumarin molecules displayed a solvatochromic effect in various solvents of varying polarity. The emission wavelength dependent fluorescence intensity was also affected by pH.

Synthesis of Nickel Spinel Ferrites Nanoparticles Coated with Thermally Reduced Graphene Oxide for EMI Shielding in the Microwave, UV, and NIR Regions.

The co-precipitation and in situ modified Hummers' method was used to synthesize Nickel Spinal Ferrites (NiFe) nanoparticles and NiFe coated with Thermally Reduced Graphene Oxide (TRGO) (NiFe-TRGO) nanoparticles, respectively. By using polyvinyl chloride (PVC), tetrahydrofuran (THF), and NiFe-TRGO, the nanocomposite film was synthesized using the solution casting technique with a thickness of 0.12-0.13 mm. Improved electromagnetic interference shielding efficiency was obtained in the 0.1-20 GHz frequency range. The initial assessment was done through XRD for the confirmation of the successful fabrication of nanoparticles and DC conductivity. The microstructure was analyzed with scanning electron microscopy. The EMI shielding was observed by incorporating a filler amount varying from 5 wt.% to 40 wt.% in three different frequency regions: microwave region (0.1 to 20 GHz), near-infrared (NIR) (700-2500 nm), and ultraviolet (UV) (200-400 nm). A maximum attenuation of 65 dB was observed with a 40% concentration of NiFe-TRGO in nanocomposite film.

Synthesis and anticancer evaluation of 2-oxo-2-(arylamino) ethyl 4-phenylpiperazine-1-carbodithioates.

Piperazine moiety is found as an efficient pharmacological scaffold in various drugs. To explore the anticancer potential of piperazine framework, a series of novel N-acetamides derivatives of phenyl piperazine containing di-thio-carbamate moiety was designed and synthesized. 1HNMR, 13CNMR, FT-IR and mass spectrometry were used for the structures elucidation of these derivatives. In-vitro cytotoxic evaluation of the prepared novel compounds against lung carcinoma A-549 was carried out using standard MTT assay. All the di-thio-carbamate-piperazine derivatives exhibited moderate to excellent cytotoxic potential against A-549 cell line based on cell viability. Particularly, 6e was found to be the most potent derivative with cell viability 34.12±0.73 % at 100 µg/mL concentration and represents promising lead compound for future progress.

Synthesis, Hemolytic Studies, and In Silico Modeling of Novel Acefylline-1,2,4-Triazole Hybrids as Potential Anti-cancer Agents against MCF-7 and A549.

A series of novel theophylline-7-acetic acid (acefylline)-derived 1,2,4-triazole hybrids with N-phenyl acetamide moieties (11a-j) have been synthesized and tested for their inhibitory (in vitro) potential against two cancer cell lines, A549 (lung) and MCF-7 (breast), using MTT assay. Among these derivatives, 11a, 11c, 11d, 11g, and 11h displayed remarkable activity against both cancer cell lines having cell viability values in the 21.74 ± 1.60-55.37 ± 4.60% range compared to acefylline (86.32 ± 1.75%) using 100 µg/µL concentration of compounds. These compounds were further screened against the A549 cancer cell line (lung) to find their half-maximal inhibitory concentration (IC50) by applying various concentrations of these compounds. Compound 11g (2-(5-((1,3-dimethyl-2,6-dioxo-2,3-dihydro-1H-purin-7(6H)-yl)methyl)-4-phenyl-4H-1,2,4-triazol-3-ylthio)-N-p-tolylacetamide) with the least IC50 value (1.25 ± 1.36 µM) was discerned as a strong inhibitor of cancer cell multiplication in both cell lines (A549 and MCF-7). Their hemolytic studies revealed that all of them had very low cytotoxicity. Finally, in silico modeling was carried out to find the mode of binding of the highly active compound (11g), which was according to the results of anti-cancer activity.

Selective Hydrogen Atom Abstraction from Dihydroflavonol by a Nonheme Iron Center Is the Key Step in the Enzymatic Flavonol Synthesis and Avoids Byproducts.

The plant non-heme iron dioxygenase flavonol synthase performs a regioselective desaturation reaction as part of the biosynthesis of the signaling molecule flavonol that triggers the growing of leaves and flowers. These compounds also have health benefits for humans. Desaturation of aliphatic compounds generally proceeds through two consecutive hydrogen atom abstraction steps from two adjacent carbon atoms and in nature often is performed by a high-valent iron(IV)-oxo species. We show that the order of the hydrogen atom abstraction steps, however, is opposite of those expected from the C-H bond strengths in the substrate and determines the product distributions. As such, flavonol synthase follows a negative catalysis mechanism. Using density functional theory methods on large active-site model complexes, we investigated pathways for desaturation and hydroxylation by an iron(IV)-oxo active-site model. Contrary to thermochemical predictions, we find that the oxidant abstracts the hydrogen atom from the strong C2-H bond rather than the weaker C3-H bond of the substrate first. We analyze the origin of this unexpected selective hydrogen atom abstraction pathway and find that the alternative C3-H hydrogen atom abstraction would be followed by a low-energy and competitive substrate hydroxylation mechanism hence, should give considerable amount of byproducts. Our computational modeling studies show that substrate positioning in flavonol synthase is essential, as it guides the reactivity to a chemo- and regioselective substrate desaturation from the C2-H group, leading to desaturation products efficiently.

Benzothiazine based acetohydrazides and acetamides as anticancer agents.

Four series of pyrazolobenzothiazine derivatives were evaluated for their anticancer activity against six different cancer cell lines i.e., KB (human oral carcinoma cells), MCF-7(human breast carcinoma cells), A549 (human alveolar adenocarcinoma cells), Hep-G2 (liver carcinoma cells), SGC-7901(human gastric carcinoma cells) and S1 (human colon carcinoma cells) using MTT assay. Among eighteen compounds tested, six compounds i.e., 1a, 1b, 1d, 4a, 4d and 4e were more active than 5-florouracil against human oral carcinoma cells (KB). Moreover, compounds 2b and 2c showed activity comparable to 5-FU against KB cell line. In addition, eight compounds were non-toxic to human PBM cells and thus exhibit selective anticancer activity.

Kinetics of photoinduced electron transfer between DNA bases and triplet 3,3',4,4'-benzophenone tetracarboxylic acid in aqueous solution of different pH's: proton-coupled electron transfer?

The kinetics of triplet state quenching of 3,3',4,4'-benzophenone tetracarboxylic acid (BPTC) by DNA bases adenine, adenosine, thymine, and thymidine has been investigated in aqueous solution using time-resolved laser flash photolysis. The observation of the BPTC ketyl radical anion at λ(max) = 630 nm indicates that one electron transfer is involved in the quenching reactions. The pH-dependence of the quenching rate constants is measured in detail. As a result, the chemical reactivity of the reactants is assigned. The bimolecular rate constants of the quenching reactions between triplet BPTC and adenine, adenosine, thymine, and thymidine are k(q) = 2.3 × 10(9) (4.7 < pH < 9.9), k(q) = 4.0 × 10(9) (3.5 < pH < 4.7), k(q) = 1.0 × 10(9) (4.7 < pH < 9.9), and k(q) = 4.0 × 10(8) M(-1) s(-1) (4.7 < pH < 9.8), respectively. Moreover, it reveals that in strong basic medium (pH = 12.0) a keto-enol tautomerism of thymine inhibits its reaction with triplet BPTC. Such a behavior is not possible for thymidine because of its deoxyribose group. In addition, the pH-dependence of the apparent electrochemical standard potential of thymine in aqueous solution was investigated by cyclic voltammetry. The ΔE/ΔpH ≈ -59 mV/pH result is characteristic of proton-coupled electron transfer. This behavior, together with the kinetic analysis, leads to the conclusion that the quenching reactions between triplet BPTC and thymine involve one proton-coupled electron transfer.