Exploring oral drug delivery: In vitro release and mathematical modeling of hydrophobic drug (Na-L-thyroxine) and its cyclodextrin inclusion complex in chitosan microparticles.

Na-l-Thyroxine (Na-l-Thy) is a frequently prescribed synthetic hormone for hypothyroidism treatment. Despite its efficacy, its hydrophobic nature poses a challenge for achieving optimal bioavailability. To address this, researchers explored various delivery methods, including micro-formulations and nano-formulations, for precise and prolonged release of hydrophobic and hydrophilic drugs. In this study, we developed micro-formulations with cyclodextrin and chitosan. Docking studies identified γ-cyclodextrin as the preferred option for forming a stable complex with Na-l-Thyroxine compared to α, and ß-cyclodextrins. Two micro-formulations were prepared compared: Na-l-Thyroxine loaded on chitosan (CS + Na-l-Thy) and Na-l-Thyroxine and γ-cyclodextrin inclusion complex (IC) loaded on chitosan (CS + IC). CS + IC exhibited superior encapsulation efficiency (91.25 %) and loading capacity (18.62 %) compared to CS + Na-l-Thy (encapsulation efficiency: 70.24 %, loading capacity: 21.18 %). Characterization using FTIR, SEM, and TGA validated successful encapsulation of Na-l-Thy in spherical microparticles with high thermal stability. In-vitro release studies at pH 1.2 and 7.4 showed that the CS + IC microparticles displayed gradual, consistent drug release compared to CS + Na-l-Thy -Thy. Both formulations showed faster release at pH 1.2 than at pH 7.4. Reaction kinetics analysis of release studies of CS + Na-l-Thy and CS + IC were best described by Higuchi kinetic model and Korsemeyer-Peppas kinetic model respectively. This study suggests that the CS + IC microparticles are an effective and stable delivery system for sustained release of hydrophobic Na-l-Thy.

Phytochemicals from Pterocarpus angolensis DC and Their Cytotoxic Activities against Breast Cancer Cells.

Pterocarpus anglonesis DC is an indigenous medicinal plant belonging to the Pterocarpus genus of the Fabaceae family. It is used to treat stomach problems, headaches, mouth ulcers, malaria, blackwater fever, gonorrhea, ringworm, diarrhea, heavy menstruation, and breast milk stimulation. Column chromatography of the stem bark extracts resulted in the isolation of eight compounds, which included friedelan-3-one (1), 3α-hydroxyfriedel-2-one (2), 3-hydroxyfriedel-3-en-2-one (3), lup-20(29)-en-3-ol (4), Stigmasta-5-22-dien-3-ol (5), 4-O-methylangolensis (6), (3ß)-3-acetoxyolean-12-en-28-oic acid (7), and tetradecyl (E)-ferulate (8). The structures were established based on NMR, IR, and MS spectroscopic analyses. Triple-negative breast cancer (HCC70), hormone receptor-positive breast cancer (MCF-7), and non-cancerous mammary epithelial cell lines (MCF-12A) were used to test the compounds' cytotoxicity. Overall, the compounds showed either no toxicity or very low toxicity to all three cell lines tested, except for the moderate toxicity displayed by lupeol (4) towards the non-cancerous MCF-12A cells, with an IC50 value of 36.60 µM. Compound (3ß)-3-acetoxyolean-12-en-28-oic acid (7) was more toxic towards hormone-responsive (MCF-7) breast cancer cells than either triple-negative breast cancer (HCC70) or non-cancerous breast epithelial (MCF-12A) cells (IC50 values of 83.06 vs. 146.80 and 143.00 µM, respectively).

Inhibitory effects of selected cannabinoids against dipeptidyl peptidase IV, an enzyme linked to type 2 diabetes.

Ethnopharmacological relevance: In recent times the decriminalisation of cannabis globally has increased its use as an alternative medication. Where it has been used in modern medicinal practises since the 1800s, there is limited scientific investigation to understand the biological activities of this plant. Aim of the study: Dipeptidyl peptidase IV (DPP-IV) plays a key role in regulating glucose homeostasis, and inhibition of this enzyme has been used as a therapeutic approach to treat type 2 diabetes. However, some of the synthetic inhibitors for this enzyme available on the market may cause undesirable side effects. Therefore, it is important to identify new inhibitors of DPP-IV and to understand their interaction with this enzyme. Methods: In this study, four cannabinoids (cannabidiol, cannabigerol, cannabinol and Δ9-tetrahydrocannabinol) were evaluated for their inhibitory effects against recombinant human DPP-IV and their potential inhibition mechanism was explored using both in vitro and in silico approaches. Results: All four cannabinoids resulted in a dose-dependent response with IC50 values of between 4.0 and 6.9 µg/mL. Kinetic analysis revealed a mixed mode of inhibition. CD spectra indicated that binding of cannabinoids results in structural and conformational changes in the secondary structure of the enzyme. These findings were supported by molecular docking studies which revealed best docking scores at both active and allosteric sites for all tested inhibitors. Furthermore, molecular dynamics simulations showed that cannabinoids formed a stable complex with DPP-IV protein via hydrogen bonds at an allosteric site, suggesting that cannabinoids act by either inducing conformational changes or blocking the active site of the enzyme. Conclusion: These results demonstrated that cannabinoids may modulate DPP-IV activity and thereby potentially assist in improving glycaemic regulation in type 2 diabetes.

Exploring the antioxidant, antimicrobial, cytotoxic and biothermodynamic properties of novel morpholine derivative bioactive Mn(ii), Co(ii) and Ni(ii) complexes - combined experimental and theoretical measurements towards DNA/BSA/SARS-CoV-2 3CLPro.

A novel class of bioactive complexes (1-3) [MII(L)2(bpy)], where, L = 2-(4-morpholinobenzylideneamino)phenol, bpy = 2,2'-bipyridine, MII = Mn (1), Co (2) or Ni (3), were assigned to octahedral geometry based on analytical and spectral measurements. Gel electrophoresis showed that complex (2) demonstrated significant DNA cleavage activity compared to the other complexes under the action of oxidation agent (H2O2). The DNA binding constant properties measured by various techniques were in the following sequence: (2) > (3) > (1) > (HL), which suggests that the complexes might intercalate DNA, a possibility that is also supported by their biothermodynamic characteristics. The binding constant results for BSA from electronic absorption and fluorometric titrations demonstrate that complex (2) exhibits the highest binding effectiveness among them all, which means that all the compounds could interact with BSA through a static approach, additionally supported by FRET measurements. DFT and docking calculations were employed to realize the electronic structure, reactivity, and interaction capability of all substances with DNA, BSA, and the SARS-CoV-2 main protease. These binding energies fell within the ranges -7.7 to -8.5, -8.2 to -10.1 and -6.7 to -9.3 kcal mol-1, respectively. The higher reactivity of the complexes than the ligand is supported by FMO theory. The in vitro antibacterial, cytotoxicity, and radical scavenging characteristics revealed that complexes (2-3) have better biological efficacy than the others. The cytotoxicity and binding properties also show good correlation with the partition coefficient (log P), which is encouraging because all of the experimental findings are closely correlated with the theoretical measurements.

Mechanochemically-Assisted Passerini Reactions: A Practical and Convenient Method for the Synthesis of Novel α-Acyloxycarboxamide Derivatives.

A carboxylic acid, an aldehyde, and an isonitrile were combined in a single step (Passerini reaction) under mechanochemical activation to produce several α-acyloxycarboxamide derivatives in high to excellent yields within 15 min of milling. Mechanochemistry, when combined with the diversity provided by multicomponent reactions, enables the efficient synthesis of the target compounds, with great atom economy, shorter reaction times, and experimental simplicity. The method allows for the rapid production of a vast library of complex compounds from a limited number of substrates.

N-Formamide as a carbonyl precursor in the catalytic synthesis of Passerini adducts under aqua and mechanochemical conditions.

A new simple, efficient, and environmentally friendly protocol is presented for the catalytic synthesis of α-acyloxycarboxamides using N-formamides as a carbonyl precursor under aqua and mechanochemical conditions. Immobilized sulfuric acid on silica gel was employed for the synthesis of desired products, via the reaction of benzoic acid, 1-napthylisocyanide and various heterocyclic N-formamides. After a careful optimization of the reaction conditions, the desired Passerini products were obtained in high to excellent yields in short reaction times (10-30 min) at room temperature. The highly efficient and environmentally friendly method provides a facile access to a library of α-acyloxycarboxamides derivatives for future research on bioactivity screening.

Aqua/Mechanochemical Mediated Synthesis of Novel Spiro [Indole-Pyrrolidine] Derivatives.

Spirocyclic scaffolds are found in many pharmacologically active natural and synthetic compounds. From time to time, efforts have been made to develop new or better processes for the synthesis of spirocyclic compounds. Spiro [Indole-pyrrolidine] Derivatives are readily synthesized in high to excellent yields by the Michael condensation of 3-dicyanomethylene-2H-indol-2-ones (produced via the Knoevenagel condensation of indole-2,3-dione with malononitrile) with isothiocyanate derivatives under aqueous and mechanochemical conditions. The advantages of this protocol are that the reactions are solvent-free, occur at ambient temperature, require short reaction times, have experimental simplicity, and produce excellent yields. These environmentally friendly reaction media are useful alternatives to volatile organic solvents.

Cytotoxicity and antimicrobial activity of isolated compounds from Monsonia angustifolia and Dodonaea angustifolia.

ETHNOPHARMACOLOGICAL RELEVANCE: Monsonia angustifolia is traditionally used to treat anthrax, heartburn, diarrhea, eye infections and hemorrhoids. Dodonaea angustifolia is frequently used as a treatment for dental pain, microbial infections and jungle fever. The two plant species were selected due to the presence of secondary metabolites such as coumarins, flavonoids, terpenoids, saponins and polyphenolics from the crude extracts, which exhibit pharmacological significance. The pure isolated compounds from the crude extracts are known for their diverse structures and interesting pharmacophores. AIM: To isolate and identify antibacterial and antifungal chemical constituents from Monsonia angustifolia and Dodonaea angustifolia plant extracts and evaluate the cytotoxicity of pure compounds from the crude extracts. MATERIALS AND METHODS: Extractives from M. angustifolia and D. angustifolia plants were isolated using chromatographic techniques and structures were elucidated based on NMR, IR and MS spectroscopic techniques. A microplate serial dilution method was used to evaluate the antibacterial activity of extracts and pure compounds against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and antifungal activity against Candida albicans and Cryptococcus neoformans. The cytotoxicity was determined using the 3-(4, 5-dimethylthiazol)-2, 5-diphenyl tetrazolium bromide (MTT) assay. RESULTS: The dichloromethane, ethyl acetate and methanol crude extracts from the plants exhibited significant inhibition of microbial growth. The phytochemical investigation of these active crude extracts led to the isolation of five pure active compounds, 5-methoxyjusticidin A (1), cis-phytyl diterpenoidal fatty acid ester (2), stigmasterol (3), ß-sitosterol (4) and 5-hydroxy-7,4'-dimethoxyflavone (5). Stigmasterol (3) showed good antifungal activity against Cryptococcus neoformans with a minimum inhibition concentration (MIC) of 25 µg/mL and Candida albicans (MIC = 50 µg/mL). CONCLUSION: Compounds (1-5) isolated from Monsonia angustifolia and Dodonaea angustifolia showed antibacterial and antifungal activities and were non-toxic against Madin-Darby canine kidney (MDCK) cells and VERO monkey kidney (VERO) cells.

New bioactive flavonoid glycosides with antioxidant activity from the stem bark of Olax subscorpioidea Oliv.

A previously unreported gallocatechin glycoside, (2 R,3S) 4'-O-methyl-gallocatechin-3-O-α-ʟ-rhamnopyranoside (1) and an unseparable mixture of two previously undescribed dihydromyricetin glycosides, (2 R,3R) 4'-O-methyl-dihydromyricetin-3-O-α-ʟ-rhamnopyranoside (2a) and (2 R,3S) 4'-O-methyl-dihydromyricetin-3-O-α-ʟ-rhamnopyranoside (2 b) along with three known compounds were isolated from the n-butanol soluble fraction of the stem bark of Olax subscorpioidea Oliv. Their structures were elucidated by detailed spectroscopic analyses, including 1H NMR, 13C NMR, 1H-1H COSY, HSQC, HMBC, NOESY, HR-ESI-MS and chemical methods. The crude ethanol extract, the fractions, and some of the isolated compounds were screened for their antioxidant and antibacterial activities. They showed significant antioxidant activities with EC50 ranging from 6.29 to 18.19 µg/mL in 2,2-diphenyl-1-picrylhydrazyl (DPPH) method and EC50 ranging from 85.77 to 86.39 mmol FeSO4/g in ferric reducing antioxidant power (FRAP) methods compared with 2.29 µg/mL and 3.52 mmol FeSO4/g for the positive control (ʟ-ascorbic acid). Nevertheless, no inhibition was observed against the tested bacterial strains at a MIC less than 256 µg/mL.

An Integrated Analysis of Mechanistic Insights into Biomolecular Interactions and Molecular Dynamics of Bio-Inspired Cu(II) and Zn(II) Complexes towards DNA/BSA/SARS-CoV-2 3CLpro by Molecular Docking-Based Virtual Screening and FRET Detection.

Novel constructed bioactive mixed-ligand complexes (1b) [CuII(L)2(phen)] and (2b) [ZnII(L)2(phen)] {where, L = 2-(4-morpholinobenzylideneamino)phenol), phen = 1,10-phenanthroline} have been structurally analysed by various analytical and spectroscopic techniques, including, magnetic moments, thermogravimetric analysis, and X-ray crystallography. Various analytical and spectral measurements assigned showed that all complexes appear to have an octahedral geometry. Agar gel electrophoresis's output demonstrated that the Cu(II) complex (1b) had efficient deoxyribonucleic cleavage and complex (2b) demonstrated the partial cleavage accomplished with an oxidation agent, which generates spreadable OH● through the Fenton type mechanism. The DNA binding constants observed from viscosity, UV-Vis spectral, fluorometric, and electrochemical titrations were in the following sequence: (1b) > (2b) > (HL), which suggests that the complexes (1b-2b) might intercalate DNA, a possibility that is supported by the biothermodynamic measurements. In addition, the observed binding constant results of BSA by electronic absorption and fluorometric titrations indicate that complex (1b) revealed the best binding efficacy as compared to complex (2b) and free ligand. Interestingly, all compounds are found to interact with BSA through a static approach, as further attested by FRET detection. The DFT and molecular docking calculations were also performed to realize the electronic structure, reactivity, and binding capability of all test samples with CT-DNA, BSA, and the SARS-CoV-2 3CLPro, which revealed the binding energies were in a range of -8.1 to -8.9, -7.5 to -10.5 and -6.7--8.8 kcal/mol, respectively. The higher reactivity of the complexes than the free ligand is supported by the FMO theory. Among all the observed data for antioxidant properties against DPPH᛫, ᛫OH, O2-• and NO᛫ free radicals, complex (1a) had the best biological efficacy. The antimicrobial and cytotoxic characteristics of all test compounds have been studied by screening against certain selected microorganisms as well as against A549, HepG2, MCF-7, and NHDF cell lines, respectively. The observed findings revealed that the activity enhances coordination as compared to free ligand via Overtone's and Tweedy's chelation mechanisms. This is especially encouraging given that in every case, the experimental findings and theoretical detections were in perfect accord.

Comprehensive Assessment of Biomolecular Interactions of Morpholine-Based Mixed Ligand Cu(II) and Zn(II) Complexes of 2,2'-Bipyridine as Potential Anticancer and SARS-CoV-2 Agents: A Synergistic Experimental and Structure-Based Virtual Screening.

A new class of pharmacologically active mixed-ligand complexes (1a-2a) [MII(L)2 (bpy)], where L = 2-(4-morpholinobenzylideneamino)phenol), bpy = 2,2'-bipyridine, MII = Cu (1a), and Zn (2a), were assigned an octahedral geometry by analytical and spectral measurements. Gel electrophoresis showed that complex (1a) demonstrated the complete DNA cleavage mediated by H2O2. The overall DNA-binding constants observed from UV-vis, fluorometric, hydrodynamic, and electrochemical titrations were in the following sequence: (1a) > (2a) > (HL), which suggests that the complexes might intercalate DNA, a possibility that is further supported by the biothermodynamic characteristics. The binding constant results of BSA by electronic absorption and fluorometric titration demonstrate that complex (1a) exhibits the highest binding effectiveness among others, which means that all compounds could interact with BSA through a static approach, additionally supported by FRET measurements. Density FunctionalTheory (DFT) and molecular docking calculations were relied on to unveil the electronic structure, reactivity, and interacting capability of all substances with DNA, BSA, and SARS-CoV-2 main protease (Mpro). These observed binding energies fell within the following ranges: -7.7 to -8.6, -7.2 to -10.2, and -6.7 to -8.2 kcal/mol, respectively. The higher reactivity of the complexes compared to free ligand is supported by the Frontier MolecularOrbital (FMO) theory. The in vitro antibacterial, cytotoxic, and radical scavenging characteristics revealed that complex (1a) has the best biological efficacy compared to others. This is encouraged because all experimental findings are closely correlated with the theoretical measurements.

A More Sustainable Isocyanide Synthesis from N-Substituted Formamides Using Phosphorus Oxychloride in the Presence of Triethylamine as Solvent.

A simple, green, and highly efficient protocol for the synthesis of isocyanides is described. The reaction involves dehydration of formamides with phosphorus oxychloride in the presence of triethylamine as solvent at 0 °C. The product isocyanides were obtained in high to excellent yields in less than 5 min. The method offers several advantages including increased synthesis speed, relatively mild conditions, and rapid access to large numbers of functionalized isocyanides, excellent purity, increased safety, and minimal reaction waste. The new approach of synthesising dehydrative isocyanides from formamides is significantly more environmentally-friendly than prior methods.

Immobilized Sulfuric Acid on Silica Gel as Highly Efficient and Heterogeneous Catalyst for the One-Pot Synthesis of Novel α-Acyloxycarboxamides in Aqueous Media.

The application of immobilized sulfuric acid on silica gel (H2SO4-SiO2) as an efficient and easily reusable solid catalyst was explored in the synthesis of novel α-acyloxycarboxamide derivatives via a Passerini reaction of benzoic acid, aldehyde/ketone, and isocyanides. The Passerini adducts were obtained in high to excellent yields within 10 min in aqueous media under catalytic conditions. The key advantages of the process include a short reaction time, high yields, the catalyst's low cost, and the catalyst's reusability.

In Vitro and In Silico Potential Inhibitory Effects of New Biflavonoids from Ochna rhizomatosa on HIV-1 Integrase and Plasmodium falciparum.

The aim of this study was to identify bioactive secondary metabolites from Ochna rhizomatosa with potential inhibitory effects against HIV and Plasmodium falciparum. A phytochemical study of O. rhizomatosa root barks resulted in the identification of three new biflavonoids (1-3), along with four known ones (4-7). Compound 7 (Gerontoisoflavone A) was a single flavonoid present in the rootbark of the plant and was used as a reference. Compound 1 (IC50 = 0.047 µM) was the only one with a noteworthy inhibitory effect against HIV-1 integrase in vitro. Chicoric acid (IC50 = 0.006 µM), a pure competitive inhibitor of HIV-1 integrase, was used as control. Compound 2 exhibited the highest antiplasmodial activity (IC50 = 4.60 µM) against the chloroquine-sensitive strain of Plasmodium falciparum NF54. Computational molecular docking revealed that compounds 1 and 2 had the highest binding score (-121.8 and -131.88 Kcal/mol, respectively) in comparison to chicoric acid and Dolutegravir (-116 and -100 Kcal/mol, respectively), towards integrase receptor (PDB:3LPT). As far as Plasmodium-6 cysteine s48/45 domain inhibition is concerned, compounds 1 and 2 showed the highest binding scores in comparison to chloroquine, urging the analysis of these compounds in vivo for disease treatment. These results confirm the potential inhibitory effect of compounds 1 and 2 for HIV and malaria treatment. Therefore, our future investigation to find inhibitors of these receptors in vivo could be an effective strategy for developing new drugs.

Effects of Tartrazine on Some Sexual Maturation Parameters in Immature Female Wistar Rats.

Over the past century, the average age for onset of puberty has declined. Several additives present in our food are thought to contribute significantly to this early puberty which is recognized to also affect people's health in later life. On this basis, the impact of 40-days unique oral administration of the food dye tartrazine (7.5, 27, and 47 mg/kg BW doses) was evaluated on some sexual maturation parameters on immature female Wistar rats. Vaginal opening was evaluated during the treatment period. At the end of the treatments, animals were sacrificed (estrus phase) and the relative weight of reproductive organs, pituitary gonadotrophin and sexual steroids level, cholesterol level in ovaries and folliculogenesis were evaluated. Compared to the control group, animals receiving tartrazine (47 mg/kg BW) showed significantly high percentage of early vaginal opening from day 45 of age, and an increase in the number of totals, primaries, secondaries, and antral follicles; a significant increase in serum estrogen, LH and in uterine epithelial thickness. Our findings suggest that tartrazine considerably disturbs the normal courses of puberty. These results could validate at least in part the global observations on increasingly precocious puberty in girls feeding increasingly with industrially processed foods.

13-amino derivatives of dehydrocostus lactone display greatly enhanced selective toxicity against breast cancer cells and improved binding energies to protein kinases in silico.

The biological activities of dehydrocostus lactone and its analogues are suggested to be mediated by the lactone ring and α,ß-methylene-γ-lactone. However, few studies exist on the structure-activity relationship of 13-amino derivatives of dehydrocostus latone. In this study new 13-amino derivatives of dehydrocostus lactone DHLC (1-4) were synthesized through Michael addition reactions, and were screened against three different breast cancer cell lines, namely hormone receptor positive breast cancer (MCF-7), triple-negative breast cancer (HCC70), and non-tumorigenic mammary epithelial (MCF-12A) cell lines. Dehydrocostus lactone (DHLC) exhibited IC50 values of 1.11 (selectivity index (SI) = 0.06), 24.70 (SI = 0.01) and 0.07 µM against HCC70, MCF-7 and MCF-12A cells, respectively. All the amino derivatives, except DHLC-3 displayed low micromolar IC50 values (ranging from 0.07-4.24 µM) against both breast cancer cell lines, with reduced toxicity towards MCF-12A non-tumorigenic mammary epithelial cells (SI values ranging from 6.00-126.86). DHLC-1 and DHLC-2 demonstrated the greatest selectivity for the MCF-7 cells (with SI of 121 and 126.86 respectively) over the MCF-12A cells. This reveals that, overall, the derivatives display greatly improved selectivity for breast cancer over non-tumorigenic mammary epithelial cells, with between 100-fold and 12 000-fold higher SI values. The improved docking scores were recorded for all the 13-amino dehydrocostus lactone derivatives for the enzymes analyzed. Compounds DHLC-4, and DHLC-3 recorded higher docking scores of -7.33 and -5.97 Kca/mol respectively, compared to the parent structure, dehydrocostus lactone (-5.34 Kca/mol) for protein kinase (PKC) theta (1XJD) and -6.22 and -5.88 Kca/mol, respectively for protein kinase iota (1RZR). The compounds further showed promising predicted adsorption, distribution, metabolisms and excretion (ADME) properties. Predicting the ADME properties of these derivatives is of importance in evaluating their drug-likeness, which could in turn be developed into potential drug candidates.

Spectro-electrochemical, fluorometric and biothermodynamic evaluation of pharmacologically active morpholine scaffold single crystal ligand and its metal(II) complexes: A comparative study on in-vitro and in-silico screening towards DNA/BSA/SARS-CoV-19.

A novel series of metal(II) complexes (1-5) [MII(L)2]{Where M = Cu (1), Co (2), Mn (3), Ni (4) and Zn (5)} constructed from 2-(4-morpholinobenzylideneamino)phenol Schiff base ligand (HL) in a 1:2 M ratio and the spectral and analytical results put forward square planar geometry. Spectro-electrochemical, hydrodynamic, gel electrophoresis, and DNA binding/cleavage results for all the compounds demonstrate that complex (1) had excellent DNA binding/cleavage properties compared to other compounds. The observation also suggests that test compounds could intercalate with DNA, and the biothermodynamic property more strongly supports the stabilizing of the double helix DNA with the complexes. BSA binding constant results show that complex (1) exposes the best binding property via a static mode, which is further confirmed by FRET calculations. The DFT calculations and docking results for all compounds towards DNA, BSA and SARS-CoV-19 main protease (3CLPro), reveal the binding energies were in the range of -7.8 to -9.4, -6.6 to -10.2 and - 6.1 - -8.2 kcal/mol for all test compounds respectively. In this case, complexes showed favorable binding energies compared to free ligand, which stimulates further studies aimed at validating the predicted activity as well as contributing to tackling the current and future viral pandemics. The in-vitro antioxidant, antimicrobial, and anticancer results for all compounds revealed that copper complex (1) has better activity compared to others. This might result in an effective anticancer drug for future research, which is especially promising since the observed experimental results for all cases were in close agreement with the theoretical calculations.

Catalytic Performance of Immobilized Sulfuric Acid on Silica Gel for N-Formylation of Amines with Triethyl Orthoformate.

In the search for convenient, green, and practical catalytic methods for the current interest in organic synthesis, a simple, green, and highly efficient protocol for N-formylation of various amines was carried out in the presence of immobilized sulfuric acid on silica gel (H2SO4-SiO2). All reactions were performed in refluxing triethyl orthoformate (65 °C). The product formamides were obtained with high-to-excellent yields within 4 min to 2 h. The current approach is advantageous, due to its short reaction time and high yields. The catalyst is recyclable with no significant loss in catalytic efficiency.

Design, Manufacturing, Characterization and Evaluation of Lipid Nanocapsules to Enhance the Biopharmaceutical Properties of Efavirenz.

Despite their incredible contribution to fighting viral infections, antiviral viral resistance is an increasing concern and often arises due to unfavorable physicochemical and biopharmaceutical properties. To address this kind of issue, lipid nanocapsules (LNC) are developed in this study, using efavirenz (EFV) as a drug model. EFV solubility was assessed in water, Labrafac Lipophile and medium chain triglycerides oil (MCT oil). EFV turned out to be more soluble in the two latter dissolving media (solubility > 250 mg/mL); hence, given its affordability, MCT oil was used for LNC formulation. LNC were prepared using a low-energy method named phase inversion, and following a design of experiments process. This one resulted in polynomial models that predicted LNC particle size, polydispersity index and zeta potential that were, respectively, around 50 nm, below 0.2 and below −33 mV, for the optimized formulations. Once synthesized, we were able to achieve an encapsulation efficacy of 87%. On the other hand, high EFV release from the LNC carrier was obtained in neutral medium as compared to acid milieu (pH 4) with, respectively, 42 and 27% EFV release within 74 h. Other characterization techniques were applied and further supported the successful encapsulation of EFV in LNCs in an amorphous form. Stability studies revealed that the developed LNC were quite stable over the period of 28 days. Ultimately, LNCs have been demonstrated to improve the biopharmaceutical properties of EFV and could therefore be used to fight against antiviral resistance.

A New Chalcone and Antimicrobial Chemical Constituents of Dracaena stedneuri.

Microbial infections are leading causes of death and morbidity all over the world due to the development of the resistance to antibiotics by certain microorganisms. In this study, the chemical exploration of the ethanol (EtOH) extract of the aerial part of Dracaena stedneuri (Dracaenaceae) led to the isolation of one previously unreported chalcone derivative, i.e., 2',4'-dihydroxy-2,3'-dimethoxychalcone (1), together with 12 known compounds: 8-(C)-methylquercetagetin-3,6,3'-trimethyl ether (2), methylgalangine (3), quercetin (4), kaempferol (5), 6,8-dimethylchrysin (6), ombuine-3-O-rutinoside (4',7-dimethylquercetin-3-O-α-L-rhamnopyranosyl-(1 → 6) -ß-D-glucopyranoside) (7), alliospiroside A (8), ß-sitosterol 3-O-glucopyranoside (9), ishigoside (10), betulinic acid (11), oleanolic acid (12), and lupeol (13). The structures were determined by spectroscopic and spectrometric analysis including 1- and 2-Dimensional Nuclear Magnetic Resonance (1D- and 2D-NMR), High-Resolution Electrospray Ionization Mass Spectrometry (HRESIMS), and comparison with literature data. The isolated secondary metabolites and crude extract displayed antibacterial activity against some multidrug-resistant strains with minimal inhibitory concentration (MIC) values ranging from 32 to 256 µg/mL. The antibacterial activity of compound 13 against Enterobacter aerogenes ATCC13048 (MIC value: 32 µg/mL) was higher than that of chloramphenicol used as the reference drug (MIC = 64 µg/mL).