SYNTHESIS AND ANTIBACTERIAL ACTIVITY OF FUSED ISOXAZOLE DERIVATIVES USING GRINDING METHOD

Objective: A facile and efficient synthesis of new pyrazoloisoxazole, isoxazolopyridine and isoxazolopyrimidine derivatives is discribed through interaction of isoxazolone derivative with different nitrogen nucleophiles. Nine of the newly synthesized compounds were tested for antibacterial activities. Methods: Interaction of isoxazolone derivative with different nitrogen nucleophiles under grinding conditions. Results: New pyrazoloisoxazole, isoxazolopyridine and isoxazolopyrimidine derivatives were synthesized and the structures of the prepared compounds were elucidated from spectral data. Conclusion: 4-(4-Chlorobenzylidene)-3-phenylisoxazol-5(4H)-one was utilized as key intermediate for the synthesis of some new heterocycles, namely pyrazoloisoxazole, isoxazolopyridine and isoxazolopyrimidine derivatives under grinding conditions. Most of the newly synthesized products revealed moderate activity against Gram-negative and Gram-positive bacteria

Synthesis of New Azoles and Azolopyrimidines Incorporating Morpholine Moiety as Potent Anti-Tumor Agents

A new series of morpholinyl-chalcones 2a–d was prepared by reaction of 2-oxo-N,4-diarylbut-3-enehydrazonoyl chlorides 1a–d with morpholine. These chalcones were used as a building block for constructing pyrazoles 3a–d and 3,4-dihydropyrimidine-2(1H)-thione 6 via their reaction with phenylhydrazine and thiourea, respectively. Moreover, a new series of azolopyrimidine derivatives 11a,b, 15, 17, 19, and 21 incorporating morpholine moiety were synthesized by reaction of 1-morpholino-4-phenyl-1-(2-phenylhydrazono)but-3-en-2-one (2a) with a number of heterocyclic amines in the presence of a catalytic amount of acetic acid. The assigned structures for all the newly synthesized compounds were confirmed on the basis of elemental analyses and spectral data and the mechanisms of their formation were also discussed. All the synthesized compounds were tested for in vitro activities against two antitumor cell lines, human lung cancer (A-549) and human hepatocellular carcinoma (HepG-2) compared with the employed standard antitumor drug (cisplatin) and the results revealed that compounds 6, 8c and 17 have promising activities compared with cisplatin. This work is licensed under a Creative Commons Attribution 4.0 International License

Efficient, Recyclable, and Heterogeneous Base Nanocatalyst for Thiazoles with a Chitosan-Capped Calcium Oxide Nanocomposite

Calcium oxide (CaO) nanoparticles have recently gained much interest in recent research due to their remarkable catalytic activity in various chemical transformations. In this article, a chitosan calcium oxide nanocomposite was created by the solution casting method under microwave irradiation. The microwave power and heating time were adjusted to 400 watts for 3 min. As it suppresses particle aggregation, the chitosan (CS) biopolymer acted as a metal oxide stabilizer. In this study, we aimed to synthesize, characterize, and investigate the catalytic potency of chitosan–calcium oxide hybrid nanocomposites in several organic transformations. The produced CS–CaO nanocomposite was analyzed by applying different analytical techniques, including Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and field-emission scanning electron microscopy (FESEM). In addition, the calcium content of the nanocomposite film was measured using energy-dispersive X-ray spectroscopy (EDS). Fortunately, the CS–CaO nanocomposite (15 wt%) was demonstrated to be a good heterogeneous base promoter for high-yield thiazole production. Various reaction factors were studied to maximize the conditions of the catalytic technique. High reaction yields, fast reaction times, and mild reaction conditions are all advantages of the used protocol, as is the reusability of the catalyst; it was reused multiple times without a significant loss of potency

Synthesis and greener pastures biological study of bis-thiadiazoles as potential Covid-19 drug candidates

A novel series of bis- (Abdelhamid et al., 2017, Banerjee et al., 2018, Bharanidharan et al., 2022)thiadiazoles was synthesized from the reaction of precursor dimethyl 2,2′-(1,2-diphenylethane-1,2-diylidene)-bis(hydrazine-1-carbodithioate) and hydrazonyl chlorides in ethanol under ultrasonic irradiation. Spectral tools (IR. NMR, MS, elemental analyses, molecular dynamic simulation, DFT and LUMO and HOMO) were used to elucidate the structure of the isolated products. Molecular docking for the precursor, 3 and ligands 6a-i to two COVID-19 important proteins M$^{pro}$ and RdRp was compared with two approved drugs, Remdesivir and Ivermectin. The binding affinity varied between the ligands and the drugs. The highest recorded binding affinity of 6c with M$^{pro}$ was (−9.2 kcal/mol), followed by 6b and 6a, (−8.9 and −8.5 kcal/mol), respectively. The lowest recorded binding affinity was (−7.0 kcal/mol) for 6 g. In comparison, the approved drugs showed binding affinity (−7.4 and −7.7 kcal/mol), for Remdesivir and Ivermectin, respectively, which are within the range of the binding affinity of our ligands. The binding affinity of the approved drug Ivermectin against RdRp recoded the highest (−8.6 kcal/mol), followed by 6a, 6 h, and 6i are the same have (−8.2 kcal/mol). The lowest reading was found for compound 3 ligand (−6.3 kcal/mol). On the other side, the amino acids also differed between the compounds studied in this project for both the viral proteins. The ligand 6a forms three H-bonds with Thr 319(A), Sr 255(A) and Arg 457(A), whereas Ivermectin forms three H-bonds with His 41(A), Gly143(A) and Gln 18(A) for viral M$^{pro}$. The RdRp amino acids residues could be divided into four groups based on the amino acids that interact with hydrogen or hydrophobic interactions. The first group contained 6d, 6b, 6 g, and Remdesivir with 1–4 hydrogen bonds and hydrophobic interactions 1 to 10. Group 2 is 6a and 6f exhibited 1 and 3 hydrogen bonds and 15 and 14 hydrophobic interactions. Group 3 has 6e and Ivermectin shows 4 and 3 hydrogen bonds, respectively and 11 hydrophobic interactions for both compounds. The last group contains ligands 3, 6c, 6 h, and 6i gave 1–3 hydrogen bonds and 6c and 3 recorded the highest number of hydrophobic interactions, 14 for both 6c and 6 h. Pro Tox-II estimated compounds’ activities as Hepatoxic, Carcinogenic and Mutagenic, revealing that 6f-h were inactive in all five similar to that found with Remdesivir and Ivermectin. The drug-likeness prediction was carried out by studying physicochemical properties, lipophilicity, size, polarity, insolubility, unsaturation, and flexibility. Generally, some properties of the ligands were comparable to that of the standards used in this study, Remdesivir and Ivermectin

Recent Progress and Potential Biomedical Applications of Electrospun Nanofibers in Regeneration of Tissues and Organs

Electrospun techniques are promising and flexible technologies to fabricate ultrafine fiber/nanofiber materials from diverse materials with unique characteristics under optimum conditions. These fabricated fibers/nanofibers via electrospinning can be easily assembled into several shapes of three-dimensional (3D) structures and can be combined with other nanomaterials. Therefore, electrospun nanofibers, with their structural and functional advantages, have gained considerable attention from scientific communities as suitable candidates in biomedical fields, such as the regeneration of tissues and organs, where they can mimic the network structure of collagen fiber in its natural extracellular matrix(es). Due to these special features, electrospinning has been revolutionized as a successful technique to fabricate such nanomaterials from polymer media. Therefore, this review reports on recent progress in electrospun nanofibers and their applications in various biomedical fields, such as bone cell proliferation, nerve regeneration, and vascular tissue, and skin tissue, engineering. The functionalization of the fabricated electrospun nanofibers with different materials furnishes them with promising properties to enhance their employment in various fields of biomedical applications. Finally, we highlight the challenges and outlooks to improve and enhance the application of electrospun nanofibers in these applications

Review of the Recent Advances in Electrospun Nanofibers Applications in Water Purification

Recently, nanofibers have come to be considered one of the sustainable routes with enormous applicability in different fields, such as wastewater treatment. Electrospun nanofibers can be fabricated from various materials, such as synthetic and natural polymers, and contribute to the synthesis of novel nanomaterials and nanocomposites. Therefore, they have promising properties, such as an interconnected porous structure, light weight, high porosity, and large surface area, and are easily modified with other polymeric materials or nanomaterials to enhance their suitability for specific applications. As such, this review surveys recent progress made in the use of electrospun nanofibers to purify polluted water, wherein the distinctive characteristics of this type of nanofiber are essential when using them to remove organic and inorganic pollutants from wastewater, as well as for oil/water (O/W) separation

Synthesis, molecular docking, and dynamic simulation targeting main protease (Mpro) of new, Thiazole clubbed pyridine scaffolds as potential COVID-19 inhibitors

Many biological activities of pyridine and thiazole derivatives have been reported, including antiviral activity and, more recently, as COVID-19 inhibitors. Thus, in this paper, we designed, synthesized, and characterized a novel series of N-aminothiazole-hydrazineethyl-pyridines, beginning with a N′-(1-(pyridine-3-yl)ethylidene)hydrazinecarbothiohydrazide derivative and various hydrazonoyl chlorides and phenacyl bromides. Their Schiff bases were prepared from the condensation of N-aminothiazole derivatives with 4-methoxybenzaldehyde. FTIR, MS, NMR, and elemental studies were used to identify new products. The binding energy for non-bonding interactions between the ligand (studied compounds) and receptor was determined using molecular docking against the SARS-CoV-2 main protease (PDB code: 6LU7). Finally, the best docked pose with highest binding energy (8a = −8.6 kcal/mol) was selected for further molecular dynamics (MD) simulation studies to verify the outcomes and comprehend the thermodynamic properties of the binding. Through additional in vitro and in vivo research on the newly synthesized chemicals, it is envisaged that the achieved results will represent a significant advancement in the fight against COVID-19

Novel Pyridinium Based Ionic Liquid Promoter for Aqueous Knoevenagel Condensation: Green and Efficient Synthesis of New Derivatives with Their Anticancer Evaluation

Herein, a distinctive dihydroxy ionic liquid ([Py-2OH]OAc) was straightforwardly assembled from the sonication of pyridine with 2-chloropropane-1,3-diol by employing sodium acetate as an ion exchanger. The efficiency of the ([Py-2OH]OAc as a promoter for the sono-synthesis of a novel library of condensed products through DABCO-catalyzed Knoevenagel condensation process of adequate active cyclic methylenes and ninhydrin was next investigated using ultimate greener conditions. All of the reactions studied went cleanly and smoothly, and the resulting Knoevenagel condensation compounds were recovered in high yields without detecting the aldol intermediates in the end products. Compared to traditional strategies, the suggested approach has numerous advantages including mild reaction conditions with no by-products, eco-friendly solvent, outstanding performance in many green metrics, and usability in gram-scale synthesis. The reusability of the ionic liquid was also studied, with an overall retrieved yield of around 97% for seven consecutive runs without any substantial reduction in the performance. The novel obtained compounds were further assessed for their in vitro antitumor potential toward three human tumor cell lines: Colo-205 (colon cancer), MCF-7 (breast cancer), and A549 (lung cancer) by employing the MTT assay, and the findings were evaluated with the reference Doxorubicin. The results demonstrated that the majority of the developed products had potent activities at very low doses. Compounds comprising rhodanine (5) or chromane (12) moieties exhibited the most promising cytotoxic effects toward three cell lines, particularly rhodanine carboxylic acid derivative (5c), showing superior cytotoxic effects against the investigated cell lines compared to the reference drug. Furthermore, automated docking simulation studies were also performed to support the results obtained

Cellulose Sulfuric Acid as an Eco-Friendly Catalyst for Novel Synthesis of Pyrido[2,3- d

A novel synthesis of a series of pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidin-5-ones has been developed from reactions of 1-(5-methyl-1-phenyl-1H-pyrazol-4-yl)-3-arylprop-2-en-1-ones and 7-amino-1,3-disubstituted[1,2,4]triazolo[4,3-a]pyrimidin-5(1H)-ones in dioxane under thermal conditions, using cellulose sulfuric acid as an eco-friendly acid catalyst. The reaction mechanism was proposed and the structures of the newly synthesized compounds were established on the basis of spectral data (mass spectrometry, infrared, 1H and 13C nuclear magnetic resonance) and elemental analyses