Structural Modifications of Nature-Inspired Indoloquinolines: A Mini Review of Their Potential Antiproliferative Activity

Cryptolepine, neocryptolepine and isocryptolepine are naturally occurring indoloquinoline alkaloids with various spectrum of biological properties. Structural modification is an extremely effective means to improve their bioactivities. This review enumerates several neocryptolepine and isocryptolepine analogues with potent antiproliferative activity against MV4-11 (leukemia), A549 (lung cancer), HCT116 (colon cancer) cell lines in vitro. Its activity towards normal mouse fibroblasts BALB/3T3 was also evaluated. Furthermore, structure activity relationships (SAR) are briefly discussed. The anticancer screening of neocryptolepine derivatives was performed in order to determine their cytotoxic and growth inhibitory activities across the JFCR39 cancer cell line panel

Emerging advanced approaches for diagnosis and inhibition of liver fibrogenesis

Abstract Background Liver fibrosis results from chronic liver injury and is characterized by excessive deposition of extracellular matrix proteins including collagen. It can progress to cirrhosis and liver failure. Main body of the abstract Multiple cellular signaling pathways drive hepatic stellate cell activation and fibrogenesis. Advances in biomarkers, imaging modalities, and omics platforms enable noninvasive diagnosis and staging of liver fibrosis. Emerging antifibrotic approaches include medications like pirfenidone, obeticholic acid, and monoclonal antibodies targeting pro-fibrotic mediators. Cell therapies using mesenchymal stem cells demonstrate antifibrotic potential through paracrine immunosuppression. Tissue-engineered liver grafts and biomaterial carriers for localized drug delivery are promising technologies. Microfluidic liver-on-a-chip platforms with patient-derived cells provide unprecedented models to study human liver fibrosis and test drug candidates. Short conclusion Significant progress has elucidated mechanisms underlying liver fibrogenesis and uncovered novel therapeutic targets. Ongoing challenges include translating preclinical findings, improving antifibrotic efficacy, and enabling personalized precision medicine approaches. Further research into combinatorial therapies, biomarkers, and tissue engineering technologies will advance the treatment of liver fibrosis from all causes

Selective lead (II) sorption using aminophosphonate-based sorbents: Effect of amine linker, characterization and sorption performance

A one-pot synthesis procedure is designed for preparing two alpha-aminophosphonate-based-sorbents (DA and TA sorbents). The reaction takes place between amine precursors (two different aliphatic amines with different chain lengths and amino group content; i.e., ethylenediamine (DA) or diethylenetriamine (TA), respectively) and both salicylaldehyde and diphenyl phosphite. Ionic liquid may be used under controlled conditions as an alternative to TiCl4 catalyst. These materials are first characterized by SEM-EDX, AFM, BET, XRD, FTIR, H-1-, C-13-, and P-31 NMR, XPS, TGA, elemental analysis (CHNP), and titration (PZC). Combined with the study of pH effect on Pb(II) sorption, FTIR and XPS analyses are used for exploring the mechanisms involved in metal binding. In a second step, the sorption properties are compared for Pb(II) recovery at pH approximate to 5. Maximum sorption is influenced by the length of the chain: DA (0.694 mmol Pb g(-1)) > TA (0.494 mmol Pb g(-1)). The sorption isotherms are modelled by the Sips equation for DA (and the Langmuir Dual Site equation) and by the Langmuir equation for TA. Thermodynamic parameters (Delta G degrees, Delta H degrees and Delta S degrees) indicate the spontaneous, endothermic nature and randomness increases during the sorption process. The uptake kinetics (equilibrium reached approximate to 120 min) is almost equally fitted by the pseudo-first-order rate equation and the pseudo-second-order rate equation. The sorbents show selective Pb(II) sorption against heavy base metals in multi-component solutions. QSAR tools (quantitative activity structure-activity relationships) are used for evaluating the correlation between their intrinsic metal characteristics and their affinities for sorbents. The sorbents are efficiently recycled for at least 5 cycles using 0.2 M HCl as the eluent (loss in sorption and desorption performances approximate to 10-14% at the fifth cycle, compared with the first cycle)

Selective lead (II) sorption using aminophosphonate-based sorbents: Effect of amine linker, characterization and sorption performance

A one-pot synthesis procedure is designed for preparing two alpha-aminophosphonate-based-sorbents (DA and TA sorbents). The reaction takes place between amine precursors (two different aliphatic amines with different chain lengths and amino group content; i.e., ethylenediamine (DA) or diethylenetriamine (TA), respectively) and both salicylaldehyde and diphenyl phosphite. Ionic liquid may be used under controlled conditions as an alternative to TiCl4 catalyst. These materials are first characterized by SEM-EDX, AFM, BET, XRD, FTIR, H-1-, C-13-, and P-31 NMR, XPS, TGA, elemental analysis (CHNP), and titration (PZC). Combined with the study of pH effect on Pb(II) sorption, FTIR and XPS analyses are used for exploring the mechanisms involved in metal binding. In a second step, the sorption properties are compared for Pb(II) recovery at pH approximate to 5. Maximum sorption is influenced by the length of the chain: DA (0.694 mmol Pb g(-1)) > TA (0.494 mmol Pb g(-1)). The sorption isotherms are modelled by the Sips equation for DA (and the Langmuir Dual Site equation) and by the Langmuir equation for TA. Thermodynamic parameters (Delta G degrees, Delta H degrees and Delta S degrees) indicate the spontaneous, endothermic nature and randomness increases during the sorption process. The uptake kinetics (equilibrium reached approximate to 120 min) is almost equally fitted by the pseudo-first-order rate equation and the pseudo-second-order rate equation. The sorbents show selective Pb(II) sorption against heavy base metals in multi-component solutions. QSAR tools (quantitative activity structure-activity relationships) are used for evaluating the correlation between their intrinsic metal characteristics and their affinities for sorbents. The sorbents are efficiently recycled for at least 5 cycles using 0.2 M HCl as the eluent (loss in sorption and desorption performances approximate to 10-14% at the fifth cycle, compared with the first cycle)

Green Synthesis of Silymarin–Chitosan Nanoparticles as a New Nano Formulation with Enhanced Anti-Fibrotic Effects against Liver Fibrosis

Background: Silymarin (SIL) has long been utilized to treat a variety of liver illnesses, but due to its poor water solubility and low membrane permeability, it has a low oral bioavailability, limiting its therapeutic potential. Aim: Design and evaluate hepatic-targeted delivery of safe biocompatible formulated SIL-loaded chitosan nanoparticles (SCNPs) to enhance SIL’s anti-fibrotic effectiveness in rats with CCl4-induced liver fibrosis. Methods: The SCNPs and chitosan nanoparticles (CNPs) were prepared by ionotropic gelation technique and are characterized by physicochemical parameters such as particle size, morphology, zeta potential, and in vitro release studies. The therapeutic efficacy of successfully formulated SCNPs and CNPs were subjected to in vivo evaluation studies. Rats were daily administered SIL, SCNPs, and CNPs orally for 30 days. Results: The in vivo study revealed that the synthesized SCNPs demonstrated a significant antifibrotic therapeutic action against CCl4-induced hepatic injury in rats when compared to treated groups of SIL and CNPs. SCNP-treated rats had a healthy body weight, with normal values for liver weight and liver index, as well as significant improvements in liver functions, inflammatory indicators, antioxidant pathway activation, and lipid peroxidation reduction. The antifibrotic activities of SCNPs were mediated by suppressing the expression of the main fibrosis mediators TGFβR1, COL3A1, and TGFβR2 by boosting the hepatic expression of protective miRNAs; miR-22, miR-29c, and miR-219a, respectively. The anti-fibrotic effects of SCNPs were supported by histopathology and immunohistochemistry (IHC) study. Conclusions: According to the above results, SCNPs might be the best suitable carrier to target liver cells in the treatment of liver fibrosis

A renewable co-solvent promoting the selective removal of lignin by increasing the total number of hydrogen bonds

Due to their low cost and excellent solubility, functional ionic liquids (ILs) have been widely used in the pretreatment of lignocellulose. However, the high viscosity and harsh pretreatment conditions of ILs usually bring difficulties in separation and regeneration, hindering the large-scale use of ILs for industrial applications. To solve these problems, four sugar-platform renewable high boiling alcohol solvents (HBS) that can form hydrogen bonds with lignin were chosen as co-solvents. This confirmed that HBS not only have an effect on the interaction of ILs and lignin, but they also participate in the interaction of the co-solvent and lignin. The cation-anion interaction energy in 2-hydroxy-N-(2-hydroxyethyl)-N-methylethanaminium methanesulfonate ([BHEM]mesy) is weakened, but for hydrogen bond interactions, like IL-lignin and co-solvent-lignin, the energy is increased, as shown by a series of characterization and analysis studies. The system has advantages, like mild reaction conditions, low cost, renewability, high biomass pretreatment efficiency, and excellent cycling performance, which can increase the lignin removal ratio to 95.2%. The recycling and reusability were also evaluated and, after seven rounds, there was no significant reduction in activity. This work provides a promising large-scale sustainable biomass pretreatment strategy for biorefinery processes

Phytochemical Characterization and Evaluation of Biological Activities of Egyptian Carob Pods (<i>Ceratonia siliqua</i> L.) Aqueous Extract: In Vitro Study

Ceratonia siliqua (Carob) is an evergreen Mediterranean tree, and carob pods are potentially nutritive and have medicinal value. The present study was carried out to estimate the possible biological activities of phytochemical-characterized carob pod aqueous extract (CPAE). The phytochemical contents of CPAE were determined by using colorimetric methods and HPLC. In addition, the free radical scavenging properties and anti-diabetic, anti-hemolytic, and antimicrobial activities were estimated by using standardized in vitro protocols. The phytochemical analysis revealed that CPAE was rich in polyphenols, flavonoids, and alkaloids, where it contained a significant amount of gallic acid, catechin, and protocatechuic acid. Furthermore, CPAE exhibited strong antioxidant activity where it prevented the formation of 2, 2-Diphenyl-1-picryl hydrazyl, hydroxyl, and nitric oxide free radicals. Additionally, it had a potent inhibitory effect against digestive enzymes (amylase, maltase, sucrase, and lactase). Moreover, CPAE exhibited anti-Staph aureus, anti-Escherichia coli, anti-Candida albicans, and anti-herpes simplex type I virus (HSV-I). Finally, CPAE protected the erythrocyte membrane from hypotonic solution-induced hemolysis. Altogether, CPAE could be regarded as an interesting source of biologically active antioxidant, anti-diabetic, and antimicrobial preparation for a potential application in pharmaceutical and food supplement fields

Facile Synthesis of Iron-Based MOFs <i>MIL-100</i>(<i>Fe</i>) as Heterogeneous Catalyst in Kabachnick Reaction

An effective technique was proposed for the synthesis of novel α-aminophosphonates: a three-component one-pot condensation reaction of aniline, aromatic aldehydes, and triphenyl phosphite in the presence of (MIL-100(Fe)) as a heterogeneous catalyst. Initially, MIL-100(Fe) was synthesized using H3BTC and ferric nitrate at low temperature and atmospheric pressure. Further, MIL-100(Fe) was characterized using various techniques such as XRD, BET surface area, scanning electron microscopy (SEM), Fourier-transform infrared (FT-IR), and thermogravimetric analysis (TGA). Herein, MIL-100(Fe) showed exceptional catalytic performance for the synthesis of α-aminophosphonate and its derivatives compared with conventional solid catalysts, and even homogeneous catalysts. The study demonstrated that MIL-100(Fe) is an ecofriendly and easily recyclable heterogeneous catalyst in Kabachnick reactions for α-aminophosphonate synthesis, with high yield (98%) and turnover frequency (TOF ~ 3.60 min−1) at room temperature and a short reaction time (30 min)

Preparation and Characterization of Silymarin-Conjugated Gold Nanoparticles with Enhanced Anti-Fibrotic Therapeutic Effects against Hepatic Fibrosis in Rats: Role of MicroRNAs as Molecular Targets

Background: The main obstacles of silymarin (SIL) application in liver diseases are its low bioavailability, elevated metabolism, rapid excretion in bile and urine, and inefficient intestinal resorption. The study aimed to synthesize and characterize silymarin-conjugated gold nanoparticles (SGNPs) formulation to improve SIL bioavailability and release for potentiating its antifibrotic action. Methods: Both SGNPs and gold nanoparticles (GNPs) were prepared and characterized using standard characterization techniques. The improved formulation was assessed for in vitro drug release study and in vivo study on rats using CCl4 induced hepatic fibrosis model. SIL, SGNPs, and GNPs were administered by oral gavage daily for 30 days. At the end of the study, rats underwent anesthesia and were sacrificed, serum samples were collected for biochemical analysis. Liver tissues were collected to measure the genes and microRNAs (miRNAs) expressions. Also, histopathological and immunohistochemistry (IHC) examinations of hepatic tissues supported these results. Results: The successful formation and conjugation of SGNPs were confirmed by measurements methods. The synthesized nanohybrid SGNPs showed significant antifibrotic therapeutic action against CCl4-induced hepatic damage in rats, and preserved normal body weight, liver weight, liver index values, retained normal hepatic functions, lowered inflammatory markers, declined lipid peroxidation, and activated the antioxidant pathway nuclear factor erythroid-2-related factor 2 (NRF2). The antifibrotic activities of SGNPs mediated through enhancing the hepatic expression of the protective miRNAs; miR-22, miR-29c, and miR-219a which results in suppressed expression of the main fibrosis mediators; TGF&beta;R1, COL3A1, and TGF&beta;R2, respectively. The histopathology and IHC analysis confirmed the anti-fibrotic effects of SGNPs. Conclusions: The successful synthesis of SGNPs with sizes ranging from 16 up to 20 nm and entrapment efficiency and loading capacity 96% and 38.69%, respectively. In vivo studies revealed that the obtained nano-formulation of SIL boosted its anti-fibrotic effects