Compounds from the Medicines for Malaria Venture Box Inhibit In Vitro Growth of Babesia divergens,a Blood-Borne Parasite of Veterinary and Zoonotic Importance

Babesiosis is an infectious disease with an empty drug pipeline. A search inside chemical libraries for novel potent antibabesial candidates may help fill such an empty drug pipeline. A total of 400 compounds (200 drug-like and 200 probe-like) from the Malaria Box were evaluated in the current study against the in vitro growth of Babesia divergens (B. divergens), a parasite of veterinary and zoonotic importance. Novel and more effective anti-B. divergens drugs than the traditionally used ones were identified. Seven compounds (four drug-like and three probe-like) revealed a highly inhibitory effect against the in vitro growth of B. divergens, with IC₅₀s ≤ 10 nanomolar. Among these hits, MMV006913 exhibited an IC₅₀ value of 1 nM IC₅₀ and the highest selectivity index of 32,000. The atom pair fingerprint (APfp) analysis revealed that MMV006913 and MMV019124 showed maximum structural similarity (MSS) with atovaquone and diminazene aceturate (DA), and with DA and imidocarb dipropionate (ID), respectively. MMV665807 and MMV665850 showed MMS with each other and with ID. Of note, a high concentration (0.75 IC₅₀) of MMV006913 caused additive inhibition of B. divergens growth when combined with DA at 0.75 or 0.50 IC₅₀. The Medicines for Malaria Venture box is a treasure trove of anti-B. divergens candidates according to the obtained results.     

Isolation,Characterization, Complete Structural Assignment,and Anticancer Activities of the Methoxylated Flavonoids from Rhamnus disperma Roots

Different chromatographic methods including reversed-phase HPLC led to the isolation and purification of three O-methylated flavonoids; 5,4’-dihydroxy-3,6,7-tri-O-methyl flavone (penduletin) (1), 5,3’-dihydroxy-3,6,7,4’,5’-penta-O-methyl flavone (2), and 5-hydroxy-3,6,7,3’,4’,5’-hexa-O-methyl flavone (3) from Rhamnus disperma roots. Additionlly, four flavonoid glycosides; kampferol 7-O-α-L-rhamnopyranoside (4), isorhamnetin-3-O-β-D-glucopyranoside (5), quercetin 7-O-α-L-rhamnopyranoside (6), and kampferol 3, 7-di-O-α-L-rhamnopyranoside (7) along with benzyl-O-β-D-glucopyranoside (8) were successfully isolated. Complete structure characterization of these compounds was assigned based on NMR spectroscopic data, MS analyses, and comparison with the literature. The O-methyl protons and carbons of the three O-methylated flavonoids (1–3) were unambiguously assigned based on 2D NMR data. The occurrence of compounds 1, 4, 5, and 8 in Rhamnus disperma is was reported here for the first time. Compound 3 was acetylated at 5-OH position to give 5-O-acetyl-3,6,7,3’,4’,5’-hexa-O-methyl flavone (9). Compound 1 exhibited the highest cytotoxic activity against MCF 7, A2780, and HT29 cancer cell lines with IC₅₀ values at 2.17 µM, 0.53 µM, and 2.16 µM, respectively, and was 2–9 folds more selective against tested cancer cell lines compared to the normal human fetal lung fibroblasts (MRC5). It also doubled MCF 7 apoptotic populations and caused G₁ cell cycle arrest. The acetylated compound 9 exhibited cytotoxic activity against MCF 7 and HT29 cancer cell lines with IC₅₀ values at 2.19 µM and 3.18 µM, respectively, and was 6–8 folds more cytotoxic to tested cancer cell lines compared to the MRC5 cells.     

Marine Brominated Tyrosine Alkaloids as Promising Inhibitors of SARS-CoV-2

There have been more than 150 million confirmed cases of SARS-CoV-2 since the beginning of the pandemic in 2019. By June 2021, the mortality from such infections approached 3.9 million people. Despite the availability of a number of vaccines which provide protection against this virus, the evolution of new viral variants, inconsistent availability of the vaccine around the world, and vaccine hesitancy, in some countries, makes it unreasonable to rely on mass vaccination alone to combat this pandemic. Consequently, much effort is directed to identifying potential antiviral treatments. Marine brominated tyrosine alkaloids are recognized to have antiviral potential. We test here the antiviral capacity of fourteen marine brominated tyrosine alkaloids against five different target proteins from SARS-CoV-2, including main protease (M^pro) (PDB ID: 6lu7), spike glycoprotein (PDB ID: 6VYB), nucleocapsid phosphoprotein (PDB ID: 6VYO), membrane glycoprotein (PDB ID: 6M17), and non-structural protein 10 (nsp10) (PDB ID: 6W4H). These marine alkaloids, particularly the hexabrominated compound, fistularin-3, shows promising docking interactions with predicted binding affinities (S-score = −7.78, −7.65, −6.39, −6.28, −8.84 Kcal/mol) for the main protease (M^pro) (PDB ID: 6lu7), spike glycoprotein (PDB ID: 6VYB), nucleocapsid phosphoprotein (PDB ID: 6VYO), membrane glycoprotein (PDB ID: 6M17), and non-structural protein 10 (nsp10) (PDB ID: 6W4H), respectively, where it forms better interactions with the protein pockets than the native interaction. It also shows promising molecular dynamics, pharmacokinetics, and toxicity profiles. As such, further exploration of the antiviral properties of fistularin-3 against SARS-CoV-2 is merited.     

The effects of variable properties on MHD unsteady natural convection heat and mass transfer over a vertical wavy surface

A mathematical model will be analyzed in order to study the effects of variables viscosity and thermal conductivity on unsteady heat and mass transfer over a vertical wavy surface in the presence of magnetic field numerically by using a simple coordinate transformation to transform the complex wavy surface into a flat plate. The fluid viscosity is assumed to vary as a exponential function of temperature and thermal conductivity is assumed to vary linearly with temperature. An implicit marching Chebyshev collocation scheme is employed for the analysis. Numerical solutions are obtained for different values of variable viscosity, variable thermal conductivity and MHD variation parameter. Numerical results show that, variable viscosity, variable thermal conductivity and MHD variation parameter have significant influences on the velocity, temperature and concentration profiles as well as for the local skin friction, Nusselt number and Sherwood number.     

Antifungal Evaluation and Molecular Docking Studies of Olea europaea Leaf Extract,Thymus vulgaris and Boswellia carteri Essential Oil as Prospective Fungal Inhibitor Candidates

Background: The present study investigated the antifungal activity and mode of action of four Olea europaea leaf extracts, Thymus vulgaris essential oil (EO), and Boswellia carteri EO against Fusarium oxysporum. Methods: Fusarium oxysporum lactucae was detected with the internal transcribed spacer (ITS) region. The chemical compositions of chloroform and dichloromethane extracts of O. europaea leaves and T. vulgaris EO were analyzed using GC-MS analysis. In addition, a molecular docking analysis was used to identify the expected ligands of these extracts against eleven F. oxysporum proteins. Results: The nucleotide sequence of the F. oxysporum lactucae isolate was deposited in GenBank with Accession No. {"type":"entrez-nucleotide","attrs":{"text":"MT249304.1","term_id":"1824655600","term_text":"MT249304.1"}}MT249304.1. The T. vulgaris EO, chloroform, dichloromethane and ethanol efficiently inhibited the growth at concentrations of 75.5 and 37.75 mg/mL, whereas ethyl acetate, and B. carteri EO did not exhibit antifungal activity. The GC-MS analysis revealed that the major and most vital compounds of the T. vulgaris EO, chloroform, and dichloromethane were thymol, carvacrol, tetratriacontane, and palmitic acid. Moreover, molecular modeling revealed the activity of these compounds against F. oxysporum. Conclusions: Chloroform, dichloromethane and ethanol, olive leaf extract, and T. vulgaris EO showed a strong effect against F. oxysporum. Consequently, this represents an appropriate natural source of biological compounds for use in healthcare. In addition, homology modeling and docking analysis are the best analyses for clarifying the mechanisms of antifungal activity.     

Organometallic Polymers of the Transition Metals

This article provides a comprehensive review of the synthesis, properties and applications of organometallic polymers of the transition metals. The different classes of organometallic polymers are described according to their structural make‐up, as well as by their methods of synthesis. A number of examples of each class are given to emphasize the richness and diversity in these areas of research. In addition to linear polymers, hyperbranched, crosslinked, star and dendritic polymers are also described. The properties that transition metal‐containing organometallic polymers possess, as well as the applications that these materials have found in various domains are highlighted.

     

Heterogeneous triopoly game with isoelastic demand function

In this paper, we analyze a triopolistic market with heterogeneous firms when the demand function is isoelastic. We consider the same heterogeneous firms as Elabbasy et al. (Comput. Math. Appl. 57:488?C499, 2009) introducing a nonlinearity in the demand function instead of the cost function. Stability conditions of the two equilibrium points and complex dynamics are studied. The main novelty consists of the double route to chaos, via period-doubling bifurcations and via Neimark?CSacker bifurcation. The two routes have important differences from the economic point of view.     

The gas-phase ozonolysis reaction of methylbutenol: A mechanistic study

The gas-phase ozonolysis reaction of methylbutenol through the Criegee mechanism is investigated. The initial reaction leads to a primary ozonide (POZ) formation with barriers in the range of 10–28 kJ mol⁻¹. The formation of 2-hydroxy-2-methyl-propanal (HMP) and formaldehyde-oxide is more favorable, by 10 kJ mol⁻¹, than the syn-CI and formaldehyde. The unimolecular dissociation of the more stable syn-CI via 1,5-H transfer into an epoxide is more favored than the epoxide and ³O₂ formation. The ester channel led to the formation of the acetone and formic acid favorably from the anti-CI. The hydration of the anti-CI with H₂O and (H₂O)₂ is significantly barrierless with a higher plausibility to the latter, and thus they may lead to the formation of peroxides and ultimately OH radicals, as well as airborne particulate matter. Reaction of anti-CI with water dimers enhances its atmospheric reactivity by a factor of 28 in reference to water monomers.     

Reaction of 2‐Phenyl‐4‐arylidene‐1,3‐oxazolones with Different Nucleophiles for Synthesis of Some New Heterocycles

Refluxing of 1,3‐oxazolone ( 1a ) with malononitrile in dry benzene and in the presence of ammonium acetate afforded imidazolone derivative ( 2 ). However, carrying out the same reaction in absolute ethanol and in the presence of piperidine as a base gave the benzamide derivative ( 4 ). Fusion of ( 1a ) with p‐anisidine gave the open adduct benzamide ( 6 ), which cyclized in acidic medium to give imidazolone derivative ( 7 ). Heating of imidazolone ( 7 ) with malononitrile above its melting point afforded 1,3‐diazepine derivative ( 8 ). Reaction of the carbohydrazide ( 9 ) with isatin in ethanol gives the corresponding Schiff base ( 11 ), which then reacted with acetyl acetone, ethyl acetoacetate, ethyl cyanoacetate, and malononitrile in n‐butanol and piperidine to afford benzamide derivative ( 13 , 14 , 15 ) and ( 16 ), respectively. The structures of the newly synthesized compounds were established on the basis of IR, ¹H‐NMR, mass spectra, and elemental analyses.     

Space‐Confined Seeded Growth of Cu Nanorods with Strong Surface Plasmon Resonance for Photothermal Actuation

Herein, we show that copper nanostructures, if made anisotropic, can exhibit strong surface plasmon resonance comparable to that of gold and silver counterparts in the near‐infrared spectrum. Further, we demonstrate that a robust confined seeded growth strategy allows the production of high‐quality samples with excellent control over their size, morphology, and plasmon resonance frequency. As an example, copper nanorods (CuNRs) are successfully grown in a limited space of preformed rod‐shaped polymer nanocapsules, thereby avoiding the complex nucleation kinetics involved in the conventional synthesis. The method is unique in that it enables the flexible control and fine‐tuning of the aspect ratio and the plasmonic resonance. We also show the high efficiency and stability of the as‐synthesized CuNRs in photothermal conversion and demonstrate their incorporation into nanocomposite polymer films that can be used as active components for constructing light‐responsive actuators and microrobots.