Synthesis, molecular docking analysis, molecular dynamic simulation, ADMET, DFT, and drug likeness studies: Novel Indeno[1,2-b]pyrrol-4(1H)-one as SARS-CoV-2 main protease inhibitors.

BACKGROUND: The COVID-19 pandemic began in 2019 as a result of the advent of a novel coronavirus, SARS-CoV-2. At present, there are a limited number of approved antiviral agents for the treatment of COVID-19. Remdesivir, Molnupiravir, and Paxlovid have been approved by the FDA to treat COVID-19 infections. Research has shown that the main protease enzyme (Mpro) of SARS-CoV-2 plays a crucial role in the enzymatic processing of viral polyproteins. This makes Mpro an interesting therapeutic target for combating infections caused by emerging coronaviruses. METHODS: The pharmacological effects of pyrroles and their derivatives have a wide range of applications. In our study, we focused on synthesizing nine novel derivatives of 2-arylamino-dihydro-indeno[1,2-b] pyrrol-4(1H)-one, with a particular emphasis on their antiviral properties. Using in silico studies involving molecular docking and DFT analyses in the gas phase using the B3LYP/6-31++G(d,p) basis set, we studied these compounds with respect to their interactions with the Mpro of SARS-CoV-2. The results of the docking analysis revealed that the synthesized compounds exhibited favorable inhibitory effects. Notably, compound 5f demonstrated the highest effectiveness against the target protein. Furthermore, the pharmacokinetic and drug-like properties of the synthesized derivatives of 2-arylamino-dihydroindeno[1,2-b] pyrrol-4(1H)-one indicated their potential as promising candidates for further development as inhibitors targeting SARS-CoV-2. However, it is imperative to determine the in vitro efficacy of these compounds through comprehensive biochemical and structural analyses.

Synthesis, docking, MD simulation, ADMET, drug likeness, and DFT studies of novel furo[2,3-b]indol-3a-ol as promising Cyclin-dependent kinase 2 inhibitors.

A new series of furo[2,3-b]indol-3a-ol derivatives was synthesized to investigate their potential as inhibitors of the Cyclin-dependent kinase 2 (CDK2) enzyme. CDK2 is a serine/threonine protein kinase belonging to a family of kinases involved in the control of the cell cycle. Based on results from clinical studies, it has been shown that overexpression of CDK2 may play a role in the development of cancer. In order to discover highly effective derivatives, a process of in silico screening was carried out. The obtained results revealed that compound 3f. had excellent binding energies. In this study, in silico screening was used to investigate protein-ligand interactions and assess the stability of the most favorable conformation. The methods utilized included molecular docking, density functional theory (DFT) calculations using the B3LYP/6-31++G(d,p) basis set in the gas phase, molecular dynamic (MD) simulation, as well as the evaluation of drug-likeness scores. The pharmacokinetic and drug-likeness properties of the novel furo[2,3-b]indol-3a-ol derivatives suggest that these compounds have the potential to be considered viable candidates for future development as anticancer drugs.

Starch mediates and cements densely magnetite-coating of talc, giving an efficient nano-catalyst for three-component synthesis of imidazo[1,2-c]quinazolines.

Hot-water-soluble starch (HWSS) was used as a powerful cementing material to produce nano-size conglomerates of talc and magnetite nanoparticles. Coordination of HWSS hydroxyl groups to iron atoms at surface of magnetite leads to grafting and encapsulation of its nanoparticles. The resulting nano-complex showed a higher loading capacity on talc than pristine magnetite nanoparticles. Only a minute amount of HWSS was detected in the fabricated nano-composite Talc\HWSS@Fe3O4. XPS study suggests a considerable interaction between HWSS and Fe3O4 nanoparticles, upon which some of the Fe+3 atoms on surface of Fe3O4 are reduced into Fe+2 atoms. ATR FT-IR spectra of the nano-composite revealed significant delamination of talc sheets on interaction with HWSS-coated Fe3O4 nanoparticles. The nano-composite displayed an efficient catalytic activity in the synthesis of new imidazo[1,2-c]quinazoline derivatives via Grobke-Blackburn-Bienaymé three-component reaction of 4-aminoquinazoline, arylaldehydes and isocyanide. The efficiency of the method was exemplified by synthesizing 7 new products in fairly high yields (68-83%) within short reaction times (24-30 min) using a catalytic amount of the catalyst under solvent-free condition at 120 °C. Clean and fast synthesis of the products and convenient separation of the robust nano-catalyst are the prominent advantages of the present method. The nano-catalyst was properly characterized.

Novel indenopyrrol-4-one derivatives as potent BRDT inhibitors: synthesis, molecular docking, drug-likeness, ADMET, and DFT studies.

We synthesized new, structurally distinct series of indeno[1,2-b]pyrrol-4(1H)-ones. Effective derivatives were found by in silico screening, and our studies revealed that compound 5h exhibited good binding energies for inhibition of BRDT. In addition, DFT studies were carried out by means of the B3LYP/6-3lG basis set in the gas phase to investigate the conformation of protein-ligand interactions. The results of the investigation suggest that these compounds could be considered novel BRDT inhibitors. The pharmacokinetic and drug-like properties of the new indenopyrrol-4(1H)-one derivatives exhibited that these compounds could be represented as potential candidates for further development into anticancer-like agents. Additionally, based on the optimised structures, the optimum geometry for each of the selected molecules was developed. Then, the estimated and the experimentally determined IR vibrational frequencies for each compound were compared. The results of this comparison showed that the theoretical and experimental data were in excellent agreement, which could support the reliability of the experimental analytical data and the applicability of the mathematical model.Communicated by Ramaswamy H. Sarma.

Ethyl 4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylate in the smiles rearrangement reaction: straightforward synthesis of amino acid derived quinolin-2(1H)-one enamines.

This paper describes the development of 4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylate compound as a heterocyclic enols containing a Michael acceptor so that it participates in an Ugi-type multicomponent condensation through a Smiles rearrangement in replacement of acid components. The new four-component containing 4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylate, aldehyde derivatives, amine derivatives and isocyanides process leads readily and efficiently to heterocyclic enamines. This report is an outstanding strategy for the preparation of new biologically structures containing peptidic or pseudo-peptidic with quinolin-2(1H)-one scaffolds.

Azole Compounds as Inhibitors of Candida albicans: QSAR Modelling.

Candida albicans is a pathogenic opportunistic yeast found in the human gut flora. It may also live outside of the human body, causing diseases ranging from minor to deadly. Candida albicans begins as a budding yeast that can become hyphae in response to a variety of environmental or biological triggers. The hyphae form is responsible for the development of multidrug resistant biofilms, despite the fact that both forms have been associated to virulence Here, we have proposed a linear and SPA-linear quantitative structure activity relationship (QSAR) modeling and prediction of Candida albicans inhibitors. A data set that consisted of 60 derivatives of benzoxazoles, benzimidazoles, oxazolo (4, 5-b) pyridines have been used. In this study, that after applying the leverage analysis method to detect outliers' molecules, the total number of these compounds reached 55. SPA-MLR model shows superiority over the multiple linear regressions (MLR) by accounting 90% of the Q 2 of anti-fungus derivatives 'activity. This paper focuses on investigating the role of SPA-MLR in developing model. The accuracy of SPA-MLR model was illustrated using leave-one-out (LOO). The mean effect of descriptors and sensitivity analysis show that RDF090u is the most important parameter affecting the as behavior of the inhibitors of Candida albicans.

Synthesis and potent antimicrobial activity of CoFe2O4 nanoparticles under visible light.

The nanoparticles of Cobalt ferrite are synthesized using polyethylene glycol as a solvent by the solvothermal method in a surfactant-free condition. Nanoparticles that were synthesized were determined by using various techniques such as Diffuse Reflection Spectroscopy (DRS), X-Ray Diffraction (XRD), Scanning Electron Microscope (SEM), and Energy Dispersive X-ray spectroscopy (EDAX). The Scanning electron microscope confirmed the range of spherical nanoparticles in the size of 20-33 nm.An excellent match was observed between the calculated particles size in the X-ray diffraction and electron microscopes results. Furthermore, their antimicrobial efficacy was determined by MIC, MBC, IC50 and disc diffusion method on Gram-negative (Pseudomonas aeruginosa and Escherichia coli) and Gram-positive (Staphylococcus aureus, Bacillus cereus) bacteria. The results indicated an acceptable bacteriostatic and bactericidal effects of this nanoparticles. Additionally, it was seen that by the increase in the concentration of nanoparticles, their antimicrobial property would increase. BACKGROUND AND OBJECTIVE: In recent years, antibacterial materials have found a special place to avoid the overuse of antibiotics. In this study, the antibacterial effects of CoFe2O4 nanoparticles on Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Bacillus cereus, were investigated due to their importance as human pathogens in nosocomial infection. METHODOLOGY: In this study, the antibacterial effects of CoFe2O4 nanoparticles such as MIC, MBC, IC50, and disc diffusion method were examined. FINDINGS: According to the results, CoFe2O4 nanoparticles exhibited potent antibacterial activity against the bacteria that were examined, especially Bacillus cereus. The MBC (Minimum Bactericidal Concentration) of CoFe2O4 nanoparticle on Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Bacillus cereus was between 0.12-0.48 mg/ml and MIC (Minimum Inhibition Concentration) on these bacteria detected between 0.06-0.24 mg/ml. The least IC50 determined for Bacillus cereus with a concentration of 0.061 mg/ml. Pseudomonas aeruginosa and Bacillus cereus identified as the most resistant and sensitive bacteria in the disc diffusion method, respectively.

Bio-assisted synthesized Ag(0) nanoparticles stabilized on hybrid of sepiolite and chitin: efficient catalytic system for xanthene synthesis.

In this work, with the use of two natural compounds, chitin and sepiolite clay, a novel covalent hybrid is fabricated and applied as a support for the stabilization of silver nanoparticles with the aid of Kombucha extract as a natural reducing agent. The resultant catalytic system, Ag@Sep-N-CH, was characterized via XRD, TEM, FTIR, ICP, SEM, TGA, UV-Vis and BET. It was found that fine Ag(0) nanoparticles with mean diameter of 6.1 ± 1.8 nm were formed on the support and the specific surface area of the catalyst was 130 m2 g-1. The study of the catalytic performance of Ag@Sep-N-CH for catalyzing synthesis of xanthenes in aqueous media under mild reaction condition confirmed that Ag@Sep-N-CH exhibited high catalytic activity and could promote the reaction of various substrates to furnish the corresponding products in high yields. Moreover, the contribution of both chitin and sepiolite to the catalysis has been affirmed. It was found that hybridization of these two components led to synergistic effects and consequently improved the observed catalytic activity. Notably, the catalyst was recyclable up to several reaction runs.

(Z)-N-[5-Bromo-2-(4-methyl-anilino)-3H-indol-3-yl-idene]-4-methyl-aniline oxide.

The crystal structure of the title compound, C(22)H(18)BrN(3)O, is stabilized by π-π contacts [centroid-centroid distance = 3.476 (2) Å] between five-membered rings as well as inter-molecular C-H⋯O and C-H⋯N hydrogen bonds. An intra-molecular N-H⋯O hydrogen bond occurs. The benzene rings make a dihedral angle of 59.89 (8)°. The dihedral angles between the fused ring systemand the two benzene rings are 3.46 (7) and 61.97 (7)°.

(2Z)-N-(4-Meth-oxy-phen-yl)-2-(4-meth-oxy-phenyl-imino)-2H-1,4-benzoxazin-3-amine.

In the crystal structure of the title compound, C(22)H(19)N(3)O(3), inter-molecular C-H⋯O hydrogen bonds link the mol-ecules into a zigzag chain parallel to the face diagonal of the ac plane. The meth-oxy phenyl rings make a dihdral angle of 32.38 (7)° and form dihedral angles of 0.66 (8) and 24.17 (7)° with the fused benzooxazine ring system.

Validated high-throughput HPLC method for the analysis of flavonol aglycones myricetin, quercetin, and kaempferol in Rhus coriaria L. using a monolithic column.

A rapid and simple reversed-phase high-performance liquid chromatographic method using a monolithic column was developed and validated for the separation and quantification of myricetin, quercetin, and kaempferol in Rhus coriaria L. The method employed the isocratic mobile phase acetonitrile-10 mM potassium dihydrogen orthophosphate buffer adjusted to pH 3.0 using orthophosphoric acid (38 + 62, v/v) at a flow rate of 4.0 mL/min; a Chromolith Performance RP-18e (100 x 4.6 mm) monolithic column kept at 40 degrees C; and UV detection at 370 nm. Although the elution order was identical and the selectivity was equivalent, the comparison between monolithic and particulate columns showed that the monolithic column could reduce the separation time to < 1 min without sacrificing column efficiency and selectivity. The method was validated according to International Conference on Harmonization guidelines. The validation characteristics included accuracy, precision, linearity, range, specificity, LOQ, and robustness. The calibration curves were linear (r > 0.999) over the concentration range of 0.88-88.3 micro/mL for myricetin, 0.95-95 microg/mL for quercetin, and 1.43-143.3 microg/mL for kaempferol. The recoveries for all three compounds were above 89%. Myricetin was found to be the major flavonol in the examined plant extracts, followed by minor quantities of quercetin and kaempferol.

A facile synthesis of novel pyrrolizidines under classical and ultrasonic conditions.

Novel pyrrolizidines (1) were synthesized from 1,3-dipolar cycloaddition of azomethine ylides and dipolarophiles (4). The reactions were highly diastereoselective and regioselective and were carried out under reflux and ultrasonic condition at room temperature. In general, milder conditions and moderate improvements in rates and reaction times were observed when ultrasonic condition was used. The products were obtained in high yields, and their structures were determined by (1)H and (13)C NMR spectral data and X-ray diffraction.

Novel rearranged abietane diterpenoids from the roots of Salvia sahendica.

Two naphthoquinone diterpenoids, 1 and 2, one tricyclic, and one tetracyclic rearranged abietane ('4,5-seco-10,5-friedo-abietane') diterpenoids, 3 and 4, respectively, together with horminone (5) have been isolated from the roots of Salvia sahendica. Compounds 2 and 3 are new, and the 13C-NMR assignment for compound 4 was modified using ' Heteronuclear Multiple-Bond Correlation' (HMBC) spectroscopic data. The structures of the compounds have been established by using different spectral data including 1D- and 2D-NMR, IR, UV, and MS. The elemental composition for the major peaks of 3 and 4 were determined by ' High-Resolution Electron Impact Mass Spectrometry' (HR-EI-MS). The relative configurations of the new compounds were determined by 1H-NMR and 'Rotating-Frame NOES' (ROESY) spectroscopy. Compounds 1, 2, and 5 showed antifungal activities when tested on Blakeslea trispora. Lapachol, a prelynated naphthoquinone, was used as a positive control. The biological activities of the related naphthoquinones and abietane diterpenoids were discussed.