Sulfadiazine analogs: anti-Toxoplasma in vitro study of sulfonamide triazoles.

Toxoplasmosis is an infection that prevails all over the world and is caused by the obligate intracellular protozoan parasite Toxoplasma gondii (T. gondii). Promising novel compounds for the treatment of T. gondii are introduced in the current investigation. In order to test their in vitro potency against T. gondii tachyzoites, six 1,2,3-triazoles-based sulfonamide scaffolds with terminal NH2 or OH group were prepared and investigated as sulfadiazine equivalents. When compared to sulfadiazine, which served as a positive control, hybrid molecules showed much more anti-Toxoplasma activity. The results showed that the IC50 of the examined compounds 3(a-f) were recoded as 0.07492 µM, 0.07455 µM, 0.0392 µM, 0.03124 µM, 0.0533 µM, and 0.01835 µM, respectively, while the sulfadiazine exhibited 0.1852 µM. The studied 1,2,3-triazole-sulfadrug molecular conjugates 3(a-f) revealed selectivity index of 10.4, 8.9, 25.4, 21, 8.3, and 29; respectively. The current study focused on the newly synthesized amino derivatives 3(d-f), as they contain the more potent amino groups which are recognized to be essential elements and promote better biological activity. Extracellular tachyzoites underwent striking morphological alterations after 2 h of treatment as seen by scanning electron microscopy (SEM). Additionally, the intracellular tachyzoite exposed to the newly synthesized amino derivatives 3(d-f) for a 24-h period of treatment revealed damaged and altered morphology by transmission electron microscopic (TEM) indicating cytopathic effects. Moreover, compound 3f underwent the most pronounced changes, indicating that it had the strongest activity against T. gondii.

Synthesis, X-ray Structure, Hirshfeld, DFT Conformational, Cytotoxic, and Anti-Toxoplasma Studies of New Indole-Hydrazone Derivatives.

The hydrazones 3a-c, were synthesized from the reaction of indole-3-carbaldehyde and nicotinic acid hydrazide, isonicotinic acid hydrazide, and benzoic acid hydrazide, respectively. Their structures were confirmed using FTIR, 1HNMR, and 13CNMR spectroscopic techniques. Exclusively, hydrazones 3b and 3c were confirmed using single crystal X-ray crystallography to exist in the Eanti form. With the aid of DFT calculations, the most stable configuration of the hydrazones 3a-c in gas phase and in nonpolar solvents (CCl4 and cyclohexane) is the ESyn form. Interestingly, the DFT calculations indicated the extrastability of the EAnti in polar aprotic (DMSO) and polar protic (ethanol) solvents. Hirshfeld topology analysis revealed the importance of the N…H, O…H, H…C, and π…π intermolecular interactions in the molecular packing of the studied systems. Distribution of the atomic charges for the hydrazones 3a-c was presented. The hydrazones 3a-c showed a polar character where 3b has the highest polarity of 5.7234 Debye compared to the 3a (4.0533 Debye) and 3c (5.3099 Debye). Regarding the anti-toxoplasma activity, all the detected results verified that 3c had a powerful activity against chronic toxoplasma infection. Compound 3c showed a considerable significant reduction percent of cyst burden in brain homogenates of toxoplasma infected mice representing 49%.

Fungal Secondary Metabolites/Dicationic Pyridinium Iodide Combinations in Combat against Multi-Drug Resistant Microorganisms.

The spread of antibiotic-resistant opportunistic microbes is a huge socioeconomic burden and a growing concern for global public health. In the current study, two endophytic fungal strains were isolated from Mangifera Indica roots and identified as Aspergillus niger MT597434.1 and Trichoderma lixii KU324798.1. Secondary metabolites produced by A. niger and T. lixii were extracted and tested for their antimicrobial activity. The highest activity was noticed against Staphylococcus aureus and E. coli treated with A. niger and T. lixii secondary metabolites, respectively. A. niger crude extract was mainly composed of Pentadecanoic acid, 14-methyl-, methyl ester and 9-Octadecenoic acid (Z)-, methyl ester (26.66 and 18.01%, respectively), while T. lixii crude extract's major components were 2,4-Decadienal, (E,E) and 9-Octadecenoic acid (Z)-, and methyl ester (10.69 and 10.32%, respectively). Moreover, a comparative study between the fungal extracts and dicationic pyridinium iodide showed that the combination of A. niger and T. lixii secondary metabolites with dicationic pyridinium iodide compound showed a synergistic effect against Klebsiella pneumoniae. The combined formulae inhibited the bacterial growth after 4 to 6 h through cell wall breakage and cells deformation, with intracellular components leakage and increased ROS production.

Bismuth Oxide Composite-Based Agricultural Waste for Wound Dressing Applications.

The purpose of this study was to enhance the antimicrobial activity of bagasse paper by coating the paper with bismuth oxide (Bi2O3) and using it to accelerate the process of wound healing. Paper sheets were prepared from sugarcane waste (bagasse). First, the paper sheets were coated with different Bi2O3 concentrations to improve the antimicrobial activity of the paper. After that, the paper sheets were allowed to dry in an oven at 50 °C for 3 h. Then, in vitro antimicrobial activity was evaluated against different microbial species, including Gram-negative bacteria (i.e., Klebsiella pneumonia, Escherichia coli) and Gram-positive bacteria (i.e., Staphylococcus aureus, Streptococcus pyogenes). The obtained results showed that the paper coated with 25% and 100% Bi2O3 had activity against all models of bacteria; however, the paper coated with 100% Bi2O3 composite had the strongest inhibitory effect. Then, bagasse paper was coated with 100% Bi2O3 and different antibiotics, to investigate their wound-healing potency in a wounded rat model for 14 days. Moreover, the paper coated with 100% Bi2O3 inhibited the cellular migration in vitro. Conclusively, coating paper with Bi2O3 enhances the wound-healing potential when applied to wounds. This impact could be ascribed to Bi2O3's broad antibacterial activity, which reduced infection and accelerated the healing process.

Targeting the interplay between MMP-2, CA II and VEGFR-2 via new sulfonamide-tethered isomeric triazole hybrids; Microwave-assisted synthesis, computational studies and evaluation.

Recently, the interest in targeting metalloenzymes is obviously growing for halting various tumor progression events and surmounting the resistance due to routine chemotherapy regimen. In this regard, attention to MMP-2 and CA II has been drawn as validated druggable anticancer targets that share vital signaling pathways. The vast majority of MMP and CA inhibitors are designed to function as directed single-target agents. In spite of their transient efficacy, they are often susceptible to tumor resistance. Hence, several dual inhibitors of correlated MMPs and CAs were introduced. This set the stage to simultaneously target the common vital signaling nodes as well. VEGFR-2 is considered central to various tumorigenesis processes involving both MMP-2 and CA II. Herein, we report concomitant inhibition of MMP-2, CA II, and VEGFR-2 via rationally designed 1,2,3- and 1,2,4-triazole hybrids bearing various sulfonamide appendages following pharmacophore hybridization strategy. The designed adducts were efficiently elaborated in an almost quantitative yield utilizing microwave-assisted click 1,3-dipolar cycloaddition reaction between various alkynes-based 1,2,4-triazole and 4-azido benzensulfonamides. All derivatives were evaluated for their anticancer potential against three human cancer cell lines (Caco-2, MDA-MB-231, and HepG-2) after safety assessment on normal human cells (Wi-38). Amongst those click adducts, 8d and 8e were the most potent and safest anticancer agents exhibiting low range nanomolar IC50 (7.37-11.96 nM) and high selectivity (SI = 3.01-4.46), against the studied cancer cell lines, hence superior to doxorubicin concerning potency (IC50 = 10.63-48.25 nM) and selectivity (SI = 0.43-1.93). They significantly elevated the expression level of the tumor suppressor p53 in the three tested cancer cell lines up to 3 folds and induced apoptosis in HepG-2 cells with higher potential to 8d over 8e. Enzymatic evaluation showed that both derivatives were potent dual MMP-2/VEGFR-2 inhibitors, particularly 8d (MMP-2; IC50 = 5.66 nM and VEGFR-2; IC50 = 6.65 nM), relative to the reference MMP-2 inhibitor NNGH (IC50 = 299.50 nM) and VEGFR-2 inhibitor sorafenib (IC50 = 4.92 nM). Both 8d and 8e exhibited relatively moderate activity against the human CA II isoform (IC50 = 116.9 and 187.5 nM, respectively) relative to the reference (IC50 = 27.3 nM). Docking studies clearly explained the superior in vitro enzymatic inhibition profiles of 8d over 8e and predicted the structural determinants of activity. Nevertheless, 8d displayed promising in silico ADMET properties and ligand efficiency metrics. These findings evidently demonstrated the sulfatriazole 8d as an auspicious multi-target-directed ligand that deserves further optimization for developing novel antitumor agents.

Novel Hybrid 1,2,4- and 1,2,3-Triazoles Targeting Mycobacterium Tuberculosis Enoyl Acyl Carrier Protein Reductase (InhA): Design, Synthesis, and Molecular Docking.

Tuberculosis (TB) caused by Mycobacterium tuberculosis is still a serious public health concern around the world. More treatment strategies or more specific molecular targets have been sought by researchers. One of the most important targets is M. tuberculosis' enoyl-acyl carrier protein reductase InhA which is considered a promising, well-studied target for anti-tuberculosis medication development. Our team has made it a goal to find new lead structures that could be useful in the creation of new antitubercular drugs. In this study, a new class of 1,2,3- and 1,2,4-triazole hybrid compounds was prepared. Click synthesis was used to afford 1,2,3-triazoles scaffold linked to 1,2,4-triazole by fixable mercaptomethylene linker. The new prepared compounds have been characterized by different spectroscopic tools. The designed compounds were tested in vitro against the InhA enzyme. At 10 nM, the inhibitors 5b, 5c, 7c, 7d, 7e, and 7f successfully and totally (100%) inhibited the InhA enzyme. The IC50 values were calculated using different concentrations. With IC50 values of 0.074 and 0.13 nM, 7c and 7e were the most promising InhA inhibitors. Furthermore, a molecular docking investigation was carried out to support antitubercular activity as well as to analyze the binding manner of the screened compounds with the target InhA enzyme's binding site.

Synthesis, Characterization and Nanoformulation of Novel Sulfonamide-1,2,3-triazole Molecular Conjugates as Potent Antiparasitic Agents.

Toxoplasma gondii (T. gondii) is a highly prevalent parasite that has no gold standard treatment due to the poor action or the numerous side effects. Focused sulfonamide-1,2,3-triazole hybrids 3a-c were wisely designed and synthesized via copper catalyzed 1,3-dipolar cycloaddition approach between prop-2-yn-1-alcohol 1 and sulfa drug azides 2a-c. The newly synthesized click products were fully characterized using different spectroscopic experiments and were loaded onto chitosan nanoparticles to form novel nanoformulations for further anti-Toxoplasma investigation. The current study proved the anti-Toxoplasma effectiveness of all examined compounds in experimentally infected mice. Relative to sulfadiazine, the synthesized sulfonamide-1,2,3-triazole (3c) nanoformulae demonstrated the most promising result for toxoplasmosis treatment as it resulted in 100% survival, 100% parasite reduction along with the remarkable histopathological improvement in all the studied organs.

Date Fruit (Phoenix dactylifera L.) Cultivar Extracts: Nanoparticle Synthesis, Antimicrobial and Antioxidant Activities.

The pharmaceutical research sector's inability to produce new drugs has made it difficult to keep up with the rate at which microbial resistance is developing. Recently, nanotechnology and its combinations with natural products have been the saviors against multidrug resistant bacteria. In the present investigation, different Egyptian and Saudi date cultivars were extracted and then phytochemically analyzed and tested for possible antimicrobial activities against multidrug resistant (MDR) microbes. The results revealed that extract of the flesh of fresh "Hayany" fruit (Egyptian date) showed the highest antimicrobial activity, with high levels of phenolic, flavonoid, and tannin concentrations (538.578 µg/mL, 28.481 µg/mL, and 20.888 µg/mL, respectively) and high scavenging activity, with an IC50 reaching 10.16 µg/mL. The highest synergistic activity was found between fresh "Hayany" fruit extract and amikacin. Novel nano-fresh fruit of "Hayany" date extract was synthesized using a ball-milling technique. The vesicle size was 21.6 nm, while the PDI and zeta potential were 0.32 and +38.4 mV, respectively. The inhibition zone diameters of nano-fresh fruit of "Hayany" date extract/amikacin reached 38 mm and 34 mm, with complete microbial eradication after 9 h and 6 h, against Candida albicans and Staphylococcus aureus, respectively. In conclusion, date fruit extract could be used as a candidate bioactive compound in the fight against infectious diseases.

Novel Novolac Phenolic Polymeric Network of Chalcones: Synthesis, Characterization, and Thermal-Electrical Conductivity Investigation.

A series of novolac phenolic polymeric networks (NPPN) were prepared via an acid-catalyzed polycondensation reaction of formaldehyde with chalcones possessing a p-phenolic OH group. When p-hydroxybenzaldehyde was treated with formaldehyde under the same conditions, a phenolic polymer (PP) was obtained. The resulting polymers were isolated in excellent yields (83-98%). Isolated polymers (NPPN, PP) were characterized using FTIR, TGA, and XRD. The results obtained from the TGA revealed that all prepared phenolic polymers have high thermal stability at high temperatures and can act as thermosetting materials. XRD data analysis showed a high degree of amorphousness for all polymers (78.8-89.2%). The electrical conductivities and resistivities of all chalcone-based phenolic networks (NPPN) and p-hydroxybenzaldehyde polymer (PP) were also determined. The physical characteristics obtained from the I-V curve showed that the conductivity of phenolic polymers has a wide range from ultimately negligible values of 0.09 µS/cm up to 2.97 µS/cm. The degree of polarization of the conjugated system's carbonyl group was attributed to high, low, or even no conductivity for all phenolic polymers since the electronic effects (inductive and mesomeric) could impact the polarization of the carbonyl group and, consequently, change the degree of the charge separation to show varied conductivity values.

Dicationic Bis-Pyridinium Hydrazone-Based Amphiphiles Encompassing Fluorinated Counteranions: Synthesis, Characterization, TGA-DSC, and DFT Investigations.

Quaternization and metathesis approaches were used to successfully design and synthesize the targeted dicationic bis-dipyridinium hydrazones carrying long alkyl side chain extending from C8 to C18 as countercation, and attracted to halide (I-) or fluorinated ion (PF6-, BF4-, CF3COO-) as counteranion. Spectroscopic characterization using NMR and mass spectroscopy was used to establish the structures of the formed compounds. In addition, their thermal properties were investigated utilizing thermogravimetric analyses (TGA), and differential scanning calorimetry (DSC). The thermal study illustrated that regardless of the alkyl group length (Cn) or the attracted anions, the thermograms of the tested derivatives are composed of three stages. The mode of thermal decomposition demonstrates the important roles of both anion and alkyl chain length. Longer chain length results in greater van der Waals forces; meanwhile, with anions of low nucleophilicity, it could also decrease the intramolecular electrostatic interaction, which leads to an overall interaction decrease and lower thermal stability. The DFT theoretical calculations have been carried out to investigate the thermal stability in terms of the Tonset. The results revealed that the type of the counteranion and chain length had a substantial impact on thermal stability, which was presumably related to the degree of intermolecular interactions. However, the DFT results illustrated that there is no dominant parameter affecting the thermal stability, but rather a cumulative effect of many factors of different extents.

Three Rings Schiff Base Ester Liquid Crystals: Experimental and Computational Approaches of Mesogenic Core Orientation Effect, Heterocycle Impact.

Three rings 2-hydroxypyridine liquid crystalline compounds have been prepared and fully characterized. The mesomorphic behavior of the prepared compounds has been investigated in terms of differential scanning calorimetry (DSC) and polarized optical microscopy (POM). Moreover, a comparative study between the prepared compounds and previously reported analogs has been discussed in terms of the orientation and position of the mesogenic core, in addition to the direction of the terminal alkyl chains. Furthermore, a detailed computational approach has been studied to illustrate the effect of geometrical and dimensional parameters on the type of the enhanced texture and the mesomorphic range and stability. The results of the DFT study revealed that the orientation of the mesogen could affect the mesomorphic behavior and this has been attributed in terms of the degree of the polarizability of the linking groups. This result has been confirmed by calculation of the net dipole moment and the molecular electrostatic potential that show how the mesogen orientation and position could impact the molecular charge separation. Finally, the effect of the pyridyl group has been also investigated in terms of the calculated aromaticity index and the π-π stacking.

Exploring the Antiparasitic Activity of Tris-1,3,4-Thiadiazoles against Toxoplasma gondii-Infected Mice.

Nitrogen-containing atoms in their core structures have been exclusive building blocks in drug discovery and development. One of the most significant and well-known heterocycles is the 1,3,4-thidiazole nucleus, which is found in a wide range of natural products and therapeutic agents. In the present work, certain tris-1,3,4-thiadiazole derivatives (6, 7) were synthesized through a multi-step synthesis approach. All synthesized compounds were characterized using different spectroscopic tools. Previously, thiadiazole compounds as anti-Toxoplasma gondii agents have been conducted and reported in vitro. However, this is the first study to test the anti-Toxoplasma gondii activity of manufactured molecular hybrids thiadiazole in an infected mouse model with the acute RH strain of T. gondii. All the observed results demonstrated compound (7)'s powerful activity, with a considerable reduction in the parasite count reaching 82.6% in brain tissues, followed by liver and spleen tissues (65.35 and 64.81%, respectively). Inflammatory and anti-inflammatory cytokines assessments proved that Compound 7 possesses potent antiparasitic effect. Furthermore, docking tests against TgCDPK1 and ROP18 kinase (two major enzymes involved in parasite invasion and egression) demonstrated compound 7's higher potency compared to compound 6 and megazol. According to the mentioned results, tris-1,3,4-thiadiazole derivatives under test can be employed as potent antiparasitic agents against the acute RH strain of T. gondii.

Anti-COVID-19 activity of some benzofused 1,2,3-triazolesulfonamide hybrids using in silico and in vitro analyses.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a pandemic fatal infection with no known treatment. The severity of the disease and the fast viral mutations forced the scientific community to search for potential solution. Here in the present manuscript, some benzofused1,2,3triazolesulfonamide hybrids were synthesized and evaluated for their anti- SARS-CoV-2 activity using in silico prediction then the most potent compounds were assessed using in-Vitro analysis. The in-Silico study was assessed against RNA dependent RNA polymerase, Spike protein S1, Main protease (3CLpro) and 2'-O-methyltransferase (nsp16). It was found that 4b and 4c showed high binding scores against RNA dependent RNA polymerase reached -8.40 and -8.75 â€‹kcal/mol, respectively compared to the approved antiviral (remdesivir -6.77 â€‹kcal/mol). Upon testing the binding score with SARS-CoV-2 Spike protein it was revealed that 4c exhibited the highest score (-7.22 â€‹kcal/mol) compared to the reference antibacterial drug Ceftazidime (-6.36 â€‹kcal/mol). Surprisingly, the two compounds 4b and 4c showed the highest binding scores against SARS-CoV-2 3CLpro (-8.75, -8.48 â€‹kcal/mol, respectively) and nsp16 (- 8.84 and - 8.89 â€‹kcal/mol, respectively) displaying many types of interaction with all the enzymes binding sites. The derivatives 4b and 4c were examined in vitro for their potential anti-SARS-CoV-2 and it was revealed that 4c was the most promising compound with IC50 reached 758.8108 â€‹mM and complete (100%) inhibition of the binding of SARS-CoV-2 virus to human ACE2 can be accomplished by using 0.01 â€‹mg.

Novel Dipyridinium Lipophile-Based Ionic Liquids Tethering Hydrazone Linkage: Design, Synthesis and Antitumorigenic Study.

Novel dicationic pyridinium ionic liquids tethering amphiphilic long alkyl side chains and fluorinated counter anions have been successfully synthesized by means of the quaternization of the dipyridinium hydrazone through its alkylation with different alkyl halides. The resulting halogenated di-ionic liquids underwent a metathesis reaction in order to incorporate some fluorinated counter anions in their structures. The structures of all the resulting di-ionic liquids were characterized by several spectroscopic experiments. The antitumorigenic activities of the investigated compounds were further studied against three different human lung cancer cell lines. Compared to the standard chemotherapeutic agent, cisplatin, the synthesized di-ionic liquids exerted equal, even more active, moderate, or weak anticancer activities against the various lung cancer cell lines under investigation. The observed anticancer activity appears to be enhanced by increasing the length of the aliphatic side chains. Moreover, dicationic pyridinium bearing a nine carbon chain as counter cation and hexafluoro phosphate and/or tetrafluoro bororate as counter anion were selected for further evaluation and demonstrated effective and significant antimetastatic effects and suppressed the colonization ability of the lung cancer cells, suggesting a therapeutic potential for the synthesized compounds in lung cancer treatment.

A New Family of Benzo[h]Chromene Based Azo Dye: Synthesis, In-Silico and DFT Studies with In Vitro Antimicrobial and Antiproliferative Assessment.

The high biological activity of the chromene compounds coupled with the intriguing optical features of azo chromophores prompted our desire to construct novel derivatives of chromene incorporating azo moieties 4a-l, which have been prepared via a three-component reaction of 1-naphthalenol-4-[(4-ethoxyphenyl) azo], 1, with the benzaldehyde derivatives and malononitrile. The structural identities of the azo-chromene 4a-l were confirmed on the basis of their spectral data and elemental analysis, and a UV-visible study was performed in a Dimethylformamide (DMF) solution for these molecules. Additionally, the antimicrobial activity was investigated against four human pathogens (Gram-positive and Gram-negative bacteria) and four fungi, employing an agar well diffusion method, with their minimum inhibitory concentrations being reported. Molecules 4a, 4g, and 4h were discovered to be more efficacious against Syncephalastrum racemosum (RCMB 05922) in comparison to the reference drugs, while compounds 4b and 4h demonstrated the highest inhibitory activity against Escherichia coli (E. coli) in evaluation against the reference drugs. Moreover, their cytotoxicity was assessed against three different human cell lines, including human colon carcinoma (HCT-116), human hepatocellular carcinoma (HepG-2), and human breast adenocarcinoma (MCF-7) with a selection of molecules illustrating potency against the HCT-116 and MCF-7 cell lines. Furthermore, the molecular modeling results depicted the binding interactions of the synthesized compounds 3b and 3h in the active site of the E. coli DNA gyrase B enzyme with a clear SAR (structure-activity relationship) analysis. Lastly, the density functional theory's (DFTs) theoretical calculations were performed to quantify the energy levels of the Frontier Molecular Orbitals (FMOs) and their energy gaps, dipole moments, and molecular electrostatic potentials. These data were utilized in the chemical descriptor estimations to confirm the biological activity.

Halting Tumor Progression via Novel Non-Hydroxamate Triazole-Based Mannich Bases MMP-2/9 Inhibitors; Design, Microwave-Assisted Synthesis, and Biological Evaluation.

Matrix metalloproteinases (MMPs) are key signaling modulators in the tumor microenvironment. Among MMPs, MMP-2 and MMP-9 are receiving renewed interest as validated druggable targets for halting different tumor progression events. Over the last decades, a diverse range of MMP-2/9 inhibitors has been identified starting from the early hydroxamic acid-based peptidomimetics to the next generation non-hydroxamates. Herein, focused 1,2,4-triazole-1,2,3-triazole molecular hybrids with varying lengths and decorations, mimicking the thematic features of non-hydroxamate inhibitors, were designed and synthesized using efficient protocols and were alkylated with pharmacophoric amines to develop new Mannich bases. After full spectroscopic characterization the newly synthesized triazoles tethering Mannich bases were subjected to safety assessment via MTT assay against normal human fibroblasts, then evaluated for their potential anticancer activities against colon (Caco-2) and breast (MDA-MB 231) cancers. The relatively lengthy bis-Mannich bases 15 and 16 were safer and more potent than 5-fluorouracil with sub-micromolar IC50 and promising selectivity to the screened cancer cell lines rather than normal cells. Both compounds upregulated p53 (2-5.6-fold) and suppressed cyclin D expression (0.8-0.2-fold) in the studied cancers, and thus, induced apoptosis. 15 was superior to 16 in terms of cytotoxic activities, p53 induction, and cyclin D suppression. Mechanistically, both were efficient MMP-2/9 inhibitors with comparable potencies to the reference prototype hydroxamate-based MMP inhibitor NNGH at their anticancer IC50 concentrations. 15 (IC50 = 0.143 µM) was 4-fold more potent than NNGH against MMP-9 with promising selectivity (3.27-fold) over MMP-2, whereas 16 was comparable to NNGH. Concerning MMP-2, 16 (IC50 = 0.376 µM) was 1.2-fold more active than 15. Docking simulations predicted their possible binding modes and highlighted the possible structural determinants of MMP-2/9 inhibitory activities. Computational prediction of their physicochemical properties, ADMET, and drug-likeness metrics revealed acceptable drug-like criteria.

Synthesis of Chitosan-La2O3 Nanocomposite and Its Utility as a Powerful Catalyst in the Synthesis of Pyridines and Pyrazoles.

Recently, the development of nanocatalysts based on naturally occurring polysaccharides has received a lot of attention. Chitosan (CS), as a biodegradable and biocompatible polysaccharide, is considered to be an excellent template for the design of a hybrid biopolymer-based metal oxide nanocomposite. In this case, lanthanum oxide nanoparticles doped with chitosan at different weight percentages (5, 10, 15, and 20 wt% CS/La2O3) were prepared via a simple solution casting method. The prepared CS/La2O3 nanocomposite solutions were cast in a Petri dish in order to produce the developed catalyst, which was shaped as a thin film. The structural features of the hybrid nanocomposite film were studied by FTIR, SEM, and XRD analytical tools. FTIR spectra confirmed the presence of the major characteristic peaks of chitosan, which were modified by interaction with La2O3 nanoparticles. Additionally, SEM graphs showed dramatic morphological changes on the surface of chitosan, which is attributed to surface adsorption with La2O3 molecules. The prepared CS/La2O3 nanocomposite film (15% by weight) was investigated as an effective, recyclable, and heterogeneous base catalyst in the synthesis of pyridines and pyrazoles. The nanocomposite used was sufficiently stable and was collected and reused more than three times without loss of catalytic activity.

Synthesis and Computational Characterization of Organic UV-Dyes for Cosensitization of Transparent Dye-Sensitized Solar Cells.

The fabrication of colorless and see-through dye-sensitized solar cells (DSCs) requires the photosensitizers to have little or no absorption in the visible light region of the solar spectrum. However, a trade-off between transparency and power conversion efficiency (PCE) has to be tackled, since most transparent DSCs are showing low PCE when compared to colorful and opaque DSCs. One strategy to increase PCE is applying two cosensitizers with selective conversion of the UV and NIR radiation, therefore, the non-visible part only is absorbed. In this study, we report synthesis of novel five UV-selective absorbers, based on diimide and Schiff bases incorporating carboxyl and pyridyl anchoring groups. A systematic computational investigation using density functional theory (DFT) and time-dependent DFT approaches was employed to evaluate their prospect of application in transparent DSCs. Experimental UV/Vis absorption spectra showed that all dyes exhibit an absorption band covering the mid/near-UV region of solar spectrum, with a bathochromic shift and a hyperchromic shifts for Py-1 dye. Computational results showed that the studied dyes satisfied the basic photophysical and energetics requirements of operating DSC as well as the stability and thermodynamical spontaneity of adsorption onto surface of TiO2. However, results revealed outperformance of the thienothiophene core-containing Py-1 UV-dye, owing to its advantageous structural attributes, improved conjugation, intense emission, large Stokes shift and maximum charge transferred to the anchor. Chemical compatibility of Py-1 dye was then theoretically investigated as a potential cosensitizer of a reference VG20-C2 NIR-dye. By the judicious selection of pyridyl anchor-based UV-absorber (Py-1) and carboxyl anchor-based NIR-absorber (VG20), the advantage of the optical complementarity and selectivity of different TiO2-adsorption-site (Lewis- and Bronsted-acidic) can be achieved. An improved overall PCE is estimated accordingly.

Solvent-Free Mechanochemical Synthesis of High Transition Biphenyltetracarboxydiimide Liquid Crystals.

A series of high temperature alkyl and alkoxy biphenyltetracarboxydiimide liquid crystals have been prepared under ball mill method using solvent-free mechanochemical approach. The thermal properties of the prepared compounds were investigated by deferential scanning calorimetry (DSC) measurements and the textures were identified by polarized optical microscope (POM). The compounds showed smectic mesomorphic behaviour. The results showed the increasing nature of transition temperature Cr-SmC with chain length with increments of the SmC mesophase range. However, the mesophase range of the SmA was decreased with the terminal chain length either for the alkyl or alkoxy terminal groups. Moreover, the DFT theoretical calculations have been conducted give a detailed projection of the structure of the prepared compounds. A conformational investigation of the biphenyl part has been studied. A deep illustration of the experimental mesomorphic behaviour has been discussed in terms of the calculated aspect ratio. A projection of the frontier molecular orbitals as well as molecular electrostatic potential has been studied to show the effect of the polarity of the terminal chains on the level and the gab of the FMOs and the distribution of electrostatic charges on the prepared molecules.

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.