Synthesis, XRD and HS-Analysis

An efficient microwave-assisted one-step synthetic route toward Mannich bases is developed from 4-hydroxyacetophenone and different secondary amines in quantitative yields, via a regioselective substitution reaction. The reaction takes a short time and is non-catalyzed and reproducible on a gram scale. The environmentally benign methodology provides a novel alternative, to the conventional methodologies, for the synthesis of mono- and disubstituted Mannich bases of 4-hydroxyacetophenone. All compounds were well-characterized by FT-IR, 1H NMR, 13C NMR, and mass spectrometry. The structures of 1-{4-hydroxy-3-[(morpholin-4-yl)methyl]phenyl}ethan-1-one (2a) and 1-{4-hydroxy-3-[(pyrrolidin-1-yl)methyl]phenyl}ethan-1-one (3a) were determined by single crystal X-ray crystallography. Compound 2a and 3a crystallize in monoclinic, P21/n, and orthorhombic, Pbca, respectively. The most characteristic features of the molecular structure of 2a is that the morpholine fragment adopts a chair conformation with strong intramolecular hydrogen bonding. Compound 3a exhibits intermolecular hydrogen bonding, too. Furthermore, the computed Hirshfeld surface analysis confirms H-bonds and π–π stack interactions obtained by XRD packing analyses

Synthesis, molecular docking and biochemical analysis of aminoalkylated naphthalene-based chalcones as acetylcholinesterase inhibitors

Twelve novel chalcones were synthesized using 2-alkyloxy-naphthaldehydes and Mannich bases of 4-hydroxyacetophenone. The chalcones were characterized using FTIR, 1D and 2D NMR and HRMS spectroscopy. Comparative docking analysis was carried out to screen their affinity towards the AChE enzyme (PDB 1EVE). All chalcones showed lower binding energy (-13.06 to -10.43 kcal/mol) against AChE better than donepezil (-10.52 kcal/mol). All chalcones were potent inhibitors towards AChE, with IC50 values ranging between 0.11 and 5.34 nM better than donepezil (IC50 33.4 nM) and selectivity indexes (0.66–23.83), despite the fact that chalcones 10 and 13 were inactive. The structure activity relationship indicated that introducing diethyl amine in ring A of the chalcone skeleton and the propargyl moiety at ring B was a?rmed to be a prospective drug against AChE. The multifunctional properties of chalcone 15 were all advantages that demonstrate an excellent candidate for the development of an effective drug against AChE

2-Benzyloxynaphthalene aminoalkylated chalcone designed as acetylcholinesterase inhibitor: Structural characterisation, in vitro biological activity and molecular docking studies

The design of an acetylcholinesterase inhibitor with multifunctional properties became the perspective for the development of an effective drug against Alzheimer's disease. Towards this target, 1-{4-hydroxy-3-[(piperidin-1-yl)methyl]phenyl}ethan-1-one (chalcone 3) was prepared and studied as an acetylcholinesterase inhibitor. The novel chalcone 3 was synthesised via Claisen-Schmidt condensation reaction with 84% yield and characterized using 1D and 2D NMR spectroscopy. The in vitro bioactivity studies of chalcone 3 demonstrated excellent inhibitory activity against AChE (IC50 1.0 nM) showing 33-fold better inhibition than donepezil, biometal chelating ability and moderate antioxidant activity. Chalcone 3 with these fascinating multifunctional proprieties can be a good candidate for the development of AD treatments. A molecular modelling investigation revealed that chalcone 3 showed dual binding inhibition of AChE enzyme. XRD shows short intra- and inter-molecular interactions with two chalcone 3 molecules per cell. Interesting Hirshfeld Surface Analysis (HSA) was conducted showing explicit agreement with the XRD analysis

Comparison of total endoscopic thyroidectomy with conventional open thyroidectomy for treatment of papillary thyroid cancer

BackgroundRecent advance of endoscopic techniques has allowed surgeons to perform thyroidectomy via an incision placement at hidden places which lead to better cosmetic acceptability compared with conventional open thyroidectomy.AimsThis study was conducted to summarize the current evidence that compare open thyroidectomy with endoscopic ‎thyroidectomy in treatment of papillary thyroid cancer‎.‎Methods An electronic literature review, including PubMed, Google Scholar, and EBSCO that examining randomized trials of endoscopic thyroidectomy (ET), conventional open thyroidectomy (COT), and management of papillary thyroid carcinoma was carried out.Results The review included 8 randomized studies that compare total endoscopic thyroidectomy versus conventional open thyroidectomy in treatment of papillary thyroid cancer. The findings showed endoscopic thyroidectomy had statically significant cosmetic appearance, less amount of blood loss and occurrence of transient hypocalcaemia than conventional open thyroidectomy in form of cosmetic outcome, amount lower blood loss.ConclusionThe current review showed that, ET has a better cosmetic outcome and lower blood loss compared with COT. While COT was associated with significantly low operation time, hospital stay, drainage time, amount of drainage fluid and transient recurrent laryngeal nerve (RLN) palsy

Synthesis, molecular docking and biochemical analysis of aminoalkylated naphthalene-based chalcones as acetylcholinesterase inhibitors

In this study, an efficient microwave-assisted one-step synthetic route towards Mannich base reactions was developed from 4-hydroxyacetophenone and different secondary amines in quantitative yields. The reaction was non-catalysed, reproducible on a gram scale and accomplished in a short time. Three derivatives of 2-alkyloxynaphthaldehydes were obtained from 2-hydroxynaphthaldehyde using the sonication method over a short time. All the precursors were characterised using infrared spectroscopy (IR), one-dimensional nuclear magnetic resonance spectroscopy (1D-NMR) and electron impact mass spectrometry (EIMS). Twelve novel chalcones were synthesised using thionyl chloride via Claisen-Schmidt condensation reaction between 2-alkyloxynaphthaldehydes and Mannich bases of 4-hydroxyacetophenone. The synthesised chalcones were characterised using IR, 1D- and 2D-NMR and high resolution mass spectrometry (HRMS). The selected chalcone (68) was used for crystallography analysis. X-ray single-crystal structural analysis revealed that chalcone (68) comprises three planar aromatic ring groups and a chair-shaped piperidine ring with intramolecular and intermolecular interactions. The synthesised chalcones were evaluated for their metal chelating properties using in situ ultraviolet (UV) and NMR titration studies. The presence of Mannich bases on the chalcone skeleton promotes the chelation capacity of the chalcone. The SwissADME web tool was used to assess the in silico drug-likeness properties, toxicity and pharmacokinetics of the novel chalcones. The Molinspiration server was used for target prediction, which showed the likelihood of the general scaffold of chalcone to be 93% enzyme inhibitor while the chalcones bearing the Mannich base could be a ChE inhibitor. Comparative docking analysis was carried out on all chalcone derivatives to screen their binding affinity towards the AChE enzyme (PDB 1EVE) using AutoDock4.2 and the results were visualised using BIOVIA Discovery Studio Visualizer. All the synthesised chalcones showed lower binding energy (-13.06 to -10.43 kcal/mol) against AChE, better than donepezil (-10.52 kcal/mol). All the chalcones were found active as antioxidants against 2,2-diphenyl-1-picrylhydrazyl with IC50 values that ranged between 12.57 and 55.52 µg/mL. The in vitro assessment of the chalcones inhibition activity against AChE and BuChE was carried out using the spectrophotometric method. All chalcones were potent inhibitors towards AChE, with IC50 values ranging between 0.11 and 5.34 nM more than donepezil (IC50 33.4 nM) and selectivity indexes (0.66–23.83), despite the fact that chalcones (71) and (74) were inactive. A correlation between the structure and inhibitory activity towards AChE of the synthesised chalcones was established. In short, introducing diethylamine in ring A of the chalcone skeleton and the propargyl moiety at ring B was affirmed to be a prospective drug against AChE. The multifunctional properties of chalcone (76) involving the potent AChE inhibitory activity (IC50 0.11 nM, SI 23.83) as well as its good antioxidant activity (IC50 40.58 µg/mL), low log P 3.87, and ability to permeate through the blood-brain barrier were all advantages that demonstrate it as an excellent candidate for the development of an effective drug against AChE

Investigation of Some Antiviral N-Heterocycles as COVID 19 Drug: Molecular Docking and DFT Calculations

The novel coronavirus, COVID-19, caused by SARS-CoV-2, is a global health pandemic that started in December 2019. The effective drug target among coronaviruses is the main protease Mpro, because of its essential role in processing the polyproteins that are translated from the viral RNA. In this study, the bioactivity of some selected heterocyclic drugs named Favipiravir (1), Amodiaquine (2), 2′-Fluoro-2′-deoxycytidine (3), and Ribavirin (4) was evaluated as inhibitors and nucleotide analogues for COVID-19 using computational modeling strategies. The density functional theory (DFT) calculations were performed to estimate the thermal parameters, dipole moment, polarizability, and molecular electrostatic potential of the present drugs; additionally, Mulliken atomic charges of the drugs as well as the chemical reactivity descriptors were investigated. The nominated drugs were docked on SARS-CoV-2 main protease (PDB: 6LU7) to evaluate the binding affinity of these drugs. Besides, the computations data of DFT the docking simulation studies was predicted that the Amodiaquine (2) has the least binding energy (−7.77 Kcal/mol) and might serve as a good inhibitor to SARS-CoV-2 comparable with the approved medicines, hydroxychloroquine, and remdesivir which have binding affinity −6.06 and −4.96 Kcal/mol, respectively. The high binding affinity of 2 was attributed to the presence of three hydrogen bonds along with different hydrophobic interactions between the drug and the critical amino acids residues of the receptor. Finally, the estimated molecular electrostatic potential results by DFT were used to illustrate the molecular docking findings. The DFT calculations showed that drug 2 has the highest of lying HOMO, electrophilicity index, basicity, and dipole moment. All these parameters could share with different extent to significantly affect the binding affinity of these drugs with the active protein sites

Crystal structure of 2-(prop-2-yn-1-yloxy)-1-naphthaldehyde, C14H10O2

C14H10O2, triclinic, P1 (no. 2), a = 7.498(3) Å, b = 7.973(3) Å, c = 9.660(4) Å, α = 67.211(13)°, β = 84.489(14)°, γ= 72.224(14)°, V = 506.8(4) Å3, Z = 2, Rgt(F) = 0.0394, wRref(F2) = 0.1135, T = 100(2) K

Microwave-Assisted Synthesis of Mono- and Disubstituted 4-Hydroxyacetophenone Derivatives via Mannich Reaction: Synthesis, XRD and HS-Analysis

An efficient microwave-assisted one-step synthetic route toward Mannich bases is developed from 4-hydroxyacetophenone and different secondary amines in quantitative yields, via a regioselective substitution reaction. The reaction takes a short time and is non-catalyzed and reproducible on a gram scale. The environmentally benign methodology provides a novel alternative, to the conventional methodologies, for the synthesis of mono- and disubstituted Mannich bases of 4-hydroxyacetophenone. All compounds were well-characterized by FT-IR, 1H NMR, 13C NMR, and mass spectrometry. The structures of 1-{4-hydroxy-3-[(morpholin-4-yl)methyl]phenyl}ethan-1-one (2a) and 1-{4-hydroxy-3-[(pyrrolidin-1-yl)methyl]phenyl}ethan-1-one (3a) were determined by single crystal X-ray crystallography. Compound 2a and 3a crystallize in monoclinic, P21/n, and orthorhombic, Pbca, respectively. The most characteristic features of the molecular structure of 2a is that the morpholine fragment adopts a chair conformation with strong intramolecular hydrogen bonding. Compound 3a exhibits intermolecular hydrogen bonding, too. Furthermore, the computed Hirshfeld surface analysis confirms H-bonds and π⁻π stack interactions obtained by XRD packing analyses

Phyto-Capped Ag Nanoparticles: Green Synthesis, Characterization, and Catalytic and Antioxidant Activities

Using a simple approach, silver nanoparticles (Ag NPs) were synthesized from green coffee bean extract. The optical color change from yellowish to reddish-brown of the green-produced Ag NPs was initially observed, which was confirmed by the UV-Visible spectrophotometer’s surface plasmonic resonance (SPR) bands at 329 and 425 nm. The functional groups of green coffee-capped Ag NPs (GC-capped Ag NPs) were studied using a Fourier transform infrared spectrometer, revealing that Ag NPs had been capped by phytochemicals, resulting in excellent stability, and preventing nanoparticle aggregation. The presence of elemental silver is confirmed by energy dispersive X-ray analysis. In addition to the measurement of the zeta potential of the prepared GC-capped Ag NPs, the size distribution is evaluated by the dynamic light scattering. Depending on the nano-morphological study, the particle diameter of Ag NPs is 8.6 ± 3.5 nm, while the particle size of GC-capped Ag NPs is 29.9 ± 4.3 nm, implying the presence of well-dispersed nanospheres with an average capsulation layer of thickness 10.7 nm. The phyto-capped Ag NPs were found to be crystalline, having a face-centered cubic (FCC) lattice structure and Ag crystallite size of ~7.2 nm, according to the XRD crystallographic analysis. The catalytic performance of phyto-capped Ag NPs in the removal of methylene blue dye by sodium borohydride (NaBH4) was investigated for 12 min to reach a degradation efficiency of approximately 96%. The scavenging activities of 2,2-Diphenyl-1-picrylhydrazyl (DPPH) free radicals are also examined in comparison to previously reported Ag-based nano-catalysts, demonstrating a remarkable IC50 of 26.88 µg/mL, which is the first time it has been recorded

Novel thiadiazole-thiazole hybrids: synthesis, molecular docking, and cytotoxicity evaluation against liver cancer cell lines

One of the worst diseases, cancer claims millions of lives each year throughout the world, necessitating the creation of novel treatments. In this study, we designed a novel series of 1,3,4-thiadiazoles through the reaction of 2-(4-methyl-2-(2-(1-phenylethylidene)hydrazineyl)thiazole-5-carbonyl)-N-phenylhydrazine-1-carbothioamide (3) with the proper hydrazonoyl halides. Using the MTT assay, the newly synthesized thiadiazoles' growth-inhibitory potential against the liver cancer cell line HepG2-1 was assessed. In comparison to the standard drug doxorubicin (IC50 = 0.72 ± 0.52 µM), the results showed that two compounds, 16b and 21 (IC50 = 0.69 ± 0.41 and 1.82 ± 0.94 µM, respectively) had promising anticancer activity. The structural activity relationship (SAR) was investigated. In addition, molecular docking analysis onto quinone oxidoreductase2 (NQO2) receptor (PDB: 4ZVM) was investigated against the potent compounds to examine the reliability of the in vitro results. The newly prepared thiadiazole-thiazole hybrids are therefore regarded as potent anticancer drugs