Grindstone Method Research Articles

Cu(II)-tyrosinase enzyme catalyst mediated synthesis of mosquito larvicidal active pyrazolidine-3,5-dione derivatives with molecular docking studies and their ichthyotoxicity analysis

The objective of this study was to develop pyrazolidine-3,5-dione derivatives with potential as environmentally friendly pesticides for pest control, specifically focusing on their efficacy as larvicidal agents. A novel one-pot synthesis of multicomponent pyrazolidine-3,5-dione derivatives (1a-m) was accomplished via the grindstone method using Cu(II)tyrosinase enzyme as a catalyst under mild reaction conditions, yielding 84%–96%. The synthesised derivatives (1a-m) were characterized using various spectroscopic methods (mass spectrometry, elemental analysis, FT-IR, and 1H and 13C NMR). NMR characterisation using DMSO-d6 as a solvent. The larvicidal and antifeedant activities of the synthesised compounds were screened and in silico computational studies were performed. The larvicidal activity against Culex quinquefasciatus and antifeedant activity against Oreochromis mossambicus were evaluated. Among the synthesised compounds, compound 1c demonstrated superior efficacy (LD50: 9.7 μg/mL) against C. quinquefasciatus compared to permethrin (LD50: 17.1 μg/mL). Regarding antifeedant activity, compounds 1a, 1e, 1f, 1j, and 1k exhibited 100% mortality at 100 μg/mL. Molecular docking analysis was performed to assess the binding capacity of a mosquito odorant-binding protein (3OGN) from Culex quinquefasciatus to compound 1c. The results revealed that compound 1c had a docking score of -10.4 kcal/mol, surpassing that of standard permethrin (-9.5 kcal/mol). Furthermore, DFT calculations were conducted to acquire theoretical data aligned with the experimental FT-IR results. According to experimental research, compound 1c demonstrates promising larvicidal activity against mosquito larvae of C. quinquefasciatus.

Synthesis of anthraquinone-connected coumarin derivatives via grindstone method and their evaluation of antibacterial, antioxidant, tyrosinase inhibitory activities with molecular docking, and DFT calculation studies

Anthraquinones and coumarins have excellent pharmacological activities and are an important class of natural plant metabolites with various biological activities. In this study, anthraquinone-9,10-dione and coumarin derivatives were combined to develop a novel anthraquinone-connected coumarin-derivative sequence. The synthesised novel anthraquinone-connected coumarin derivatives (1a-t) were screened for in vitro antibacterial, antioxidant, and tyrosinase inhibitory activities. The antibacterial activities of the synthesised compounds (1a–t) were tested against both gram-positive and gram-negative bacteria. Specifically, compound 1t was more active against E. aerogenes than ciprofloxacin. With regard to antioxidant activity, compound 1o (50.68 % at 100 μg/mL) was highly active compared to the other compounds, whereas it was less active than the standard BHT (76.74 % at 100 μg/mL). In terms of compound 1r (9.31 ± 0.45 μg/mL) was highly active against tyrosinase inhibitory activity compared with kojic acid (10.42 ± 0.98 μg/mL). In the molecular docking study, compound 1r had a higher docking score (−8.8 kcal mol−1) than kojic acid (−1.7 kcal mol−1). DFT calculations were performed to determine the energy gap of highly active compound 1r (ΔE = 0.11) and weakly active compound 1a (ΔE = 0.12). In this study, we found that every molecule displayed significant antibacterial, antioxidant, and tyrosinase inhibitory properties. Based on these reports, compounds 1r and 1t may act as multi-target agents.

Synthesis of a New Series of Anthraquinone-Linked Cyclopentanone Derivatives: Investigating the Antioxidant, Antibacterial, Cytotoxic and Tyrosinase Inhibitory Activities of the Mushroom Tyrosinase Enzyme Using Molecular Docking.

New bioactive anthraquinone derivatives are investigated for antibacterial, tyrosinase inhibitory, antioxidant cytotoxic activity, and molecular docking. The compounds were produced using the grindstone method, yielding 69 to 89%. These compounds were analyzed using IR, 1H, and 13C NMR and elemental and mass spectral methods. Additionally, the antibacterial, antioxidant, and tyrosinase inhibitory activities of all the synthesised compounds were evaluated. Compound 2 showed remarkable tyrosinase inhibition activity, with an (IC50: 13.45 µg/mL), compared to kojic acid (IC50: 19.40 µg/mL). It also exhibited moderate antioxidant and antibacterial activities with respect to the references BHT and ampicillin, respectively. Kinetic analysis revealed that the tyrosinase inhibitory activity of compound 2 was non-competitive and competitive, whereas that of compound 1 was low. All compounds (1-8) were significantly less active than doxorubicin (LC50: 0.74±0.01μg/mL). However, compound 2 affinity for the 2Y9X protein was lower than kojic acid, with a lower docking score (-8.6 kcal/mol compared to (-4.7 kcal/mol), making it more effective. All synthesized compounds displayed remarkable antibacterial, tyrosinase inhibitory, antioxidant, and cytotoxic activities, with compound 2 showing exceptional potency as a multitarget agent. Anthraquinone substituent groups may offer the potential for the development of treatments. The derivatives were synthesized using the grindstone method, and their antibacterial, antioxidant, tyrosinase inhibitory, and cytotoxic activities were inspected. Molecular docking and molecular dynamics simulations were performed using compound 2 and kojic acid to validate the results and confirm the stability of the compounds.

In silico Study and Solvent-free one-pot Synthesis of Tetrahydropyrimidine derivatives by Mechanochemistry Approach for Targeting Human Neutrophil Elastase against Lung Cancer.

Pyrimidine derivative has evinced its biological importance in targeting lung cancer by inhibiting neutrophil elastase. All THPM derivatives were synthesized by the grindstone method at ambient temperature followed by molecular docking study for efficient binding interaction of THPM compounds by targeting human neutrophil elastase (HNE) (PDB ID: 5A0A) and In-silico ADMET study using PkCSM. Moreover, all synthesized compounds were characterized by spectroscopy techniques and screened for anti-cancer activity using in vitro HNE assay kit. We reported a one-pot solvent-free mechanochemical approach for synthesizing tetrahydropyrimidine (THPM) derivatives from various aromatic aldehydes, ethyl cyanoacetate, and urea followed by in silico study and evaluation against human neutrophil elastase (HNE) for treatment of lung cancer. We calibrated the best molecules that bound to specific targets more efficiently using a molecular docking approach and provided the desired efficacy. In-silico ADMET studies revealed that all best-scored compounds had drug-like characteristics for potential use as human neutrophil elastase inhibitors (HNE) in lung cancer treatment. Additionally, the in vitro studies revealed that compounds 1, 2, and 8 show potent HNE inhibitory activity for lung cancer treatment. In a nutshell, the tetrahydropyrimidine (THPM) scaffold and its derivatives may serve as potential HNE inhibitors for the development of a promising anti-cancer agent.

Mosquito larvicidal activity of pyrrolidine-2,4-dione derivatives: An investigation against Culex quinquefasciatus and molecular docking studies

The pyrrolidine-2,4-dione derivatives were used to conduct a larvicidal test on Culex quinquefasciatus larvae of the second instar. Mannich base condensation method was used to synthesis the pyrrolidine-2,4-dione derivatives by grindstone method. The reaction conditions were mild, resulting in high yields. An analysis of the synthesized compounds was carried out using FTIR, 1H NMR, 13C NMR, mass spectrometry, and elemental analysis. Synthesized compounds (1a-h) were evaluated for larvicidal activities. Compound 1e (LD50: 26.06 µg/mL), and 1f (LD50: 26.89 µg/mL), and were notably more active against Culex quinquefasciatus than permethrin (LD50: 26.14 µg/mL). The docking studies also demonstrated that 1e, and 1f are potent larvicides with higher binding energy (−12.6 kcal/mol) than the control in the mosquito odorant binding protein (PDB ID: 3OGN). The larvicidal properties of lead molecules have made them important for use as insecticides.

Larvicidal Activity of Geranylacetone Derivatives against Culex quinquefasciatus Larvae and Investigation of Environmental Toxicity and Non-Target Aquatic Species

A grindstone method based on Mannich condensation was used to synthesize geranylacetone derivatives (1a–1f). The method showed a high yield under milder reaction conditions. Analyses of the synthesized compounds were carried out by FTIR, 1H, 13C NMR, mass spectrometry, and elemental analysis. We synthesized and evaluated the larvicidal and ichthyotoxic activities of six compounds (1a–1f) in this study. Compound 1f (5,9-dimethyl-1-phenyl-3-(2-(3-phenylallylidene)hydrazinyl)deca-4,8-dien-1-one) was more active (LD50: 14.1 µg/mL) against the second instar larvae of Culex quinquefasciatus than geranylacetone (67.2 µg/mL), whereas the former caused 13.9% mortality at 100 µg/mL. Geranylacetone, in an antifeedant screening test, showed 53.1% against Oreochromis mossambicus within 24 h. The compound 1f showed high larvicidal activity against C. quinquefasciatus and was non-toxic to non-target aquatic species.

Tyrosinase-mediated synthesis of larvicidal active 1,5-diphenyl pent-4-en-1-one derivatives against Culex quinquefasciatus and investigation of their ichthyotoxicity

1,5-diphenylpent-4-en-1-one derivatives were synthesised using the grindstone method with Cu(II)-tyrosinase used as a catalyst. This method showed a high yield under mild reaction conditions. The synthesised compounds were identified by FTIR, 1H NMR, 13C NMR, mass spectrometry, and elemental analysis. In this study, a total of 17 compounds (1a–1q) were synthesised, and their larvicidal and antifeedant activities were evaluated. Compound 1i (1-(5-oxo-1,5-diphenylpent-1-en-3-yl)-3-(3-phenylallylidene)thiourea) was notably more active (LD50: 28.5 µM) against Culex quinquefasciatus than permethrin(54.6 µM) and temephos(37.9 µM), whereas compound 1i at 100 µM caused 0% mortality in Oreochromis mossambicus within 24 h in an antifeedant screening, with ichthyotoxicity determined as the death ratio (%) at 24 h. Compounds 1a, 1e, 1f, 1j, and 1k were found to be highly toxic, whereas 1i was not toxic in antifeedant screening. Compound 1i was found to possess a high larvicidal activity against C. quinquefasciatus and was non-toxic to non-target aquatic species. Molecular docking studies also supported the finding that 1i is a potent larvicide with higher binding energy than the control (− 10.0 vs. − 7.6 kcal/mol) in the 3OGN protein. Lead molecules are important for their larvicidal properties and application as insecticides.

Dopamine-Mediated Vanillin Multicomponent Derivative Synthesis via Grindstone Method: Application of Antioxidant, Anti-Tyrosinase, and Cytotoxic Activities.

PurposeThis study aimed to determine the extent of contribution of dopamine to antioxidant and anti-tyrosinase activities, by dopamine addition to vanillin. This study achieved the synthesis of dopamine-associated vanillin Mannich base derivatives prepared via a one-step reaction involving a green chemistry approach, and investigation of antioxidant and anti-tyrosinase activities.MethodsNovel one-pot synthesis of Mannich base dopamine-connected vanillin (1a-l) derivatives can be achieved via green chemistry without using a catalyst. Newly-prepared compounds were characterised with FTIR and NMR (1H and 13C) spectra, mass spectra, and elemental analyses. In total, 12 compounds (1a-l) were synthesised and their antioxidant and anti-tyrosinase activities evaluated. Antioxidant activities of 2,2-diphenyl-1-picrylhydrazyl (DPPH), nitric oxide (NO), hydrogen peroxide (H2O2), and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and diammonium assays, ABTS•+ radical scavenging, and linoleic acid peroxidation were used to screen all synthesised compounds (1a-l) for anti-tyrosinase activities and cytotoxicity against MCF-7 and Vero cell lines;.ResultsThe compound 1k inhibited (IC50:11.02µg/mL) the DPPH-scavenging activity to a greater extent than the standard BHT (IC50:25.17µg/mL), and showed high activity in H2O2 and NO scavenging assays. Compound 1e was more potent (96.21%) against ABTS and compound 1k was more potent (95.28%) against 2,2ʹ-azobis(2-amidinopropane)dihydrochloride antioxidant than the standard trolox. All synthesised compounds were screened for anti-tyrosinase inhibitory activity. Compound 1e had higher activity against tyrosinase (IC50=10.63 µg/mL), than kojic acid (IC50=21.52µg/mL), and was more cytotoxic (GI50 0.01µM) against MCF-7 cell line than the doxorubicin standard and other tested compounds.ConclusionIn this study, all compounds were found to possess significant antioxidant and anti-tyrosinase activities. Compounds 1e and 1k performed well, compared with other compounds, in all assays. In addition, this study successfully identified several promising molecules that exhibited antioxidant and anti-tyrosinase activities.

Antineoplastic Activity of Alkylaminolapachol Analogues and their Copper Complexes against MDA-MB-231 Human Breast Cancer Cell Lines

In present study, three alkylamino substituted hydroxynaphthoquinone analogues of naturally occurring bioactive lapachol are synthesized. Further, copper(II) complexes of these ligands have been synthesized using hassle free modified grindstone method. Both ligands and copper(II) complexes were characterized using UV-visible spectroscopy, FTIR, elemental analysis and NMR spectra. Cell viability assay of the compound was carried out against growth of MDA-MB-231 human breast cancer cell lines. A better tumorocidal activity was observed for ligands and their copper(II) complexes in concentration of 2.95 to 0.11 mmol/L. Antineoplastic activity of copper(II) complexes was found to be more than parent ligands. Antimicrobial assay results showed that compound exhibit better activity against organisms under study. Antimicrobial susceptibility of compounds was carried out against culture of E. coli K12 (RP4), B. subtilis (pUB110), K. pneumoniae and S. paratyphi. The lowest MIC of < 0.20 mg/mL was obtained for L-3 against S. paratyphi. Cyclic voltammetry of ligand and complexes performed in non-aqueous system shows that ligand exhibits classical two step redox couple corresponds to the formation of semiquinone and catechole moieties in solution state at characteristic potential values. Whereas cyclic voltammogram of copper(II) complexes exhibit additional peak at characteristic potential corresponds to reversible redox reaction of central Cu(II) ion in complexes.

Synthesis of schiff base compound from vanillin and aniline volume variations of acid catalyst from Belimbing Wuluh using grindstone method

Schiff base compound was a product between carbonyl and primary amine compounds in acidic conditions. Based on several studies, the compound had activity as a corrosion inhibitor. Schiff base compounds were synthesized from vanillin and aniline using natural acid catalysts from Belimbing Wuluh (Averrhoa Blimbi L.) with volume variations 0; 0.25; 0.5; and 1 mL and grinded for 10 minutes. The synthesized compound was characterized by its physical properties. Further characterization included a UV-Vis spectrophotometer, FTIR and GC-MS. The corrosion inhibition efficiency on metals was carried out in HCl 1M. Synthesized compounds were yellowish-white solids, slightly soluble in water, and had a melting point at 149-151°C. The yield with volume variations 0; 0.25; 0.5; and 1 mL in a row were 96.84; 93.81; 92.45 and 89.69%. The synthesized compound had wavelengths 283-284 and 325-330 nm. This compound had an imine bond (-C=N-) with wavenumber 1584.909 – 1585.974 cm−1. The product with a 0 mL catalyst was characterized by GC-MS and showed a peak with retention time 24.173 minutes and m/z 227. It had a similarity with the molecular weight of the 2-methoxy-4- ((phenylamino)methyl)phenol compound. The inhibition efficiency of these compounds was 39.38 to 77.40%.

Green & sustainable nanocatalysed synthetic route for an exploration of knoevenagel condensation

Indole-3-carbaldehyde has a wide variety of applications, as a versatile synthon in organic chemistry, also found to be remarkably active as 12- & 15- lipoxygenase inhibitors, anti-tumour, antimicrobial and anti-inflammatory agents. In this work, we report the synthesis of targeted knoevenagel condensed products of indole-3-carbaledehydes (1a–e) and active methylene containing moieties 3-methyl-1-phenyl-5-pyrazolone (A) in the presence of ZnO nanoparticles by using solvent free grindstone method and compared with traditional refluxing method. Grindstone method for preparation of libraries of these knoevenagel condensed products lead to many advantages in terms of excellent yields, short reaction time, high reaction rate and also attracts the attention from the environment point of view as well as economic perspective. All the synthesized compounds have been characterized by their IR, 1H NMR, and Q-TOF mass spectral data and elemental analyses.

Urea nitrate catalyzed synthesis of 2-arylbenzothiazoles using the grindstone technique

Abstract An efficient, green and environmentally friendly grindstone method for the synthesis of 2-arylbenzothiazole derivatives in the presence of urea nitrate as the catalyst under solvent-free conditions was developed. All products were characterized by elemental analysis and spectral methods.

Sulfated choline ionic liquid-catalyzed acetamide synthesis by grindstone method

Sulfated choline ionic liquid (SCIL) has been found to be an efficient solid acid IL catalyst for the protection of amine groups with acetic anhydride under solvent-free grindstone conditions. The attractive features of this new catalytic methodology include its sustainability, facile work-up procedure, economic viability, and biodegradability. The SCIL catalyst was characterized using infrared spectroscopy, wide-angle X-ray scattering analysis, and scanning electron microscopy with energy dispersive X-ray spectroscopy. The catalyst could be reused six times without significant loss in activity. Furthermore, no chromatographic separations were needed to obtain the desired products.

Facile and Green Syntheses of Unsymmetrically Substituted 3-(1-Benzyl-1H-indol-3-yl)-2-(1-ethyl-1H-indole-3-carbonyl)-acrylonitrile and Study of their Antimicrobial Activities

Facile and green syntheses of unsymmetrically substituted-3-(1-benzyl-1H-indol-3-yl)-2-(1- ethyl-1H-indole-3-carbonyl)-acrylonitriles 5(a-d) is being reported. L-tryptophan has been utilized as an efficient and eco-friendly catalyst in the solvent free condition under the grind stone method at room temperature for Knoevenagel condensation of N-benzyl indole-3-carboxyaldehyde (2) with the active methylene compounds, 3-cyanoacetylindole 3(a-d) at room temperature to afford substituted- 3-(1-benzyl-1H-indol-3-yl)-2-(1H-indole-3-carbonyl)-acrylonitrile 4(a-d) respectively. Subsequently these products were treated with DES and K2CO3 in the solvent free condition under the grind stone method at room temperature to afford the corresponding substituted-3-(1-benzyl-1H-indol-3-yl)-2- (1-ethyl-1H-indole-3-carbonyl)-acrylonitrile 5(a-d). The antibacterial and antifungal activities of 4(a-d) and 5(a-d) have been studied.

L-Tyrosine as an Eco-Friendly and Efficient Catalyst for Knoevenagel Condensation of Arylaldehydes with Meldrum’s Acid in Solvent-Free Condition under Grindstone Method

We investigate L-Tyrosine as an efficient catalyst for the Knoevenagel condensation of arylaldehydes with meldrum’s acid containing cyclic active methylene group in solvent-free condition under grindstone method at room temperature to produce substituted-5-benzylidene-2,2-dimethyl-[1,3]dioxane-4,6-diones 3(a–j).

Simple and practical procedure for Knoevenagel condensation under solvent-free conditions

The Knoevenagel condensation reaction between araldehyde and active methylene using gallium chloride catalyst under solvent-free conditions has been described. The reaction takes place at room temperature by grind stone method and offers good purity of product in high yield. Work-up is very simple and the products do not need further purification. The reaction conditions are very mild and this protocol is applicable to various aldehydes such as araldehydes and heteroaromatic aldehydes as well as active methylene compounds, namely, malononitrile or ethyl cyanoacetate. [Display omitted]

Mechanochemistry: An efficient method of solvent-free synthesis of 3-amino-2,4-dicarbonitrile-5-methylbiphenyls

3-Amino-2,4-dicarbonitrile-5-methylbiphenyls are synthesized by a three-component reaction of aromatic aldehydes, malononitrile, and acetone in the presence of catalytic NaOMe under grindstone method. The yields are excellent; the procedure is simple, efficient, and environmentally benign; and all the reactions go to completion within 2–3 min.

Zn(OAc)2 · 2H2O-Catalyzed, Simple, and Clean Procedure for the Synthesis of 2-Substituted Benzoxazoles Using a Grindstone Method

Zn(OAc)2 · 2H2O efficiently catalyzes the condensation reaction between 2-aminophenol and various araldehydes to afford the 2-substituted benzoxazoles in good to excellent yields. The remarkable features of this protocol are simple and mild reaction conditions, use of readily available catalyst, and shorter reaction time, and in addition the reaction proceeds just by grinding the substrates and catalyst without any solvent and hence matches the green chemistry protocols.

ChemInform Abstract: Sodium Carbonate: A Versatile Catalyst for Knoevenagel Condensation.

AbstractAn efficient synthesis based on the grindstone method is shown.

Lithium hydroxide: A simple and an efficient catalyst for Knoevenagel condensation under solvent-free Grindstone method

Synthesis of arylmethylidenes from araldehydes and active methylene compounds catalyzed by catalytic amount of lithium hydroxide (LiOH·H2O) in the absence of a solvent under Grindstone method is reported. The reactions go to completion within 1–5min and give products in excellent yields at 26°C.