Development and In Vitro characterization of Azadirachta Indica Gum grafted polyacrylamide Based pH-Sensitive Hydrogels to improve the Bioavailability of Lansoprazole.

The present study intended to develop a pH-responsive hydrogel based on Neem gum (Ng) to improve Lansoprazole (LSP) oral bioavailability. pH-responsive hydrogel formulations (F1-F9) were prepared using different Ng ratios, Acrylamide (AAm), and methylene-bis-acrylamide (MBA). The formulated hydrogels were characterized through FTIR, thermal analysis, swelling ratio, SEM, sol-gel ratios, In-Vitro drug release, and cytotoxicity analysis. Azadirachta Indica was extracted to produce a powder containing 21.5 % Ng. Prepared hydrogels showed maximum swelling at pH 7.4, whereas the swelling at an acidic pH was insignificant. LSP-loaded hydrogel demonstrated a regulated release of LSP for up to 24 h and indicated a Super Case II transport release mechanism. During the cytotoxic evaluation, the delivery system showed minimal cytotoxicity towards normal cells, while percent cytotoxicity was carried out for a longer duration (up to 96 h). The present study revealed Azadirachta indica gum-based pH-responsive hydrogel as a promising technique for precisely delivering LSP.

Synthesis, characterization, pharmacological and computational evaluation of hyaluronic acid modified chebulinic acid encapsulated chitosan nanocomposite for cancer therapy.

The purpose of this study was to produce hyaluronic acid customized nanoparticles with chitosan for the delivery of chebulinic acid (CLA) to enhance its anticancer potential against breast cancer. A significant portion of CLA was encapsulated (89.72 ± 4.38 %) and loaded (43.15 ± 5.61 %) within hybrid nanoparticles. The colloidal hybrid nanoparticles demonstrated a polydispersity index (PDI) of about 0.379 ± 0.112, with zeta capacitance of 32.69 ± 5.12 (mV), and an average size of 115 ± 8 (nm). It was found that CLA-CT-HA-NPs had stronger anticancer effects on MCF-7 cells (IC50 = 8.18 ± 3.02 µM) than pure CLA (IC50 = 17.15 ± 5.11 µM). The initial cytotoxicity findings were supported by additional investigations based on comet assay and flow cytometry analysis. Tumor remission and survival were evaluated in five separate groups of mice. When juxtaposed with pure CLA (3.17 ± 0.419 %), CLA-CT-HA-NPs improved survival rates and reduced tumor burden by 3.76 ± 0.811(%). Furthermore, in-silico molecular docking investigations revealed that various biodegradable polymers had several levels of compatibility with CLA. The outcomes of this study might potentially served as an effective strategy for delivering drugs in the context of breast cancer therapy.

Fabrication and evaluation of anticancer potential of diosgenin incorporated chitosan-silver nanoparticles; in vitro, in silico and in vivo studies.

The discovery of effective therapeutic approaches with minimum side effects and their tendency to completely eradicate the disease is the main challenge in the history of cancer treatment. Fenugreek (FGK) seeds are a rich source of phytochemicals, especially Diosgenin (DGN), which shows outstanding anticancer activities. In the present study, chitosan-silver nanoparticles (ChAgNPs) containing Diosgenin (DGN-ChAgNPs) were synthesized and evaluated for their anticancer activity against breast cancer cell line (MCF-7). For the physical characterization, the hydrodynamic diameter and zeta potential of DGN-ChAgNPs were determined to be 160.4 ± 12 nm and +37.19 ± 5.02 mV, respectively. Transmission electron microscopy (TEM) showed that nanoparticles shape was mostly round with smooth edges. Moreover, DGN was efficiently entrapped in nanoformulation with good entrapment efficacy (EE) of ~88 ± 4 %. The in vitro anti-proliferative activity of DGN-ChAgNPs was performed by sulforhodamine B (SRB) assay with promising inhibitory concentration of 6.902 ± 2.79 µg/mL. DAPI staining, comet assay and flow cytometry were performed to validate the anticancer potential of DGN-ChAgNPs both qualitatively and quantitatively. The percentage of survival rate and tumor reduction weight was evaluated in vivo in different groups of mice. Cisplatin was used as a standard anticancer drug. The DGN-ChAgNPs (12.5 mg/kg) treated group revealed higher percentage of survival rate and tumor reduction weight as compared to pure DGN treated group. These findings suggest that DGN-ChAgNPs could be developed as potential treatment therapy for breast cancer.

Preparation and investigation of a novel combination of Solanum nigrum-loaded, arabinoxylan-cross-linked ß-cyclodextrin nanosponges for the treatment of cancer: in vitro, in vivo, and in silico evaluation.

Introduction: Cancer contributes to a high mortality rate worldwide spanning its diversity from genetics to resistant therapeutic response. To date emerging strategies to combat and manage cancer are particularly focused on the development of targeted therapies as conventional treatments account for the destruction of normal cells as well. In this regard, medicinal plant-based therapies are quite promising in imposing minimal side effects; however, limitations like poor bioavailability and stability of bioactive phytochemicals are associated with them. In parallel, nanotechnology provides nominal solution to deliver particular therapeutic agent without compromising its stability. Methods: In this study, Solanum nigrum, an effective medicinal plant, loaded arabinoxylan cross-linked ß-cyclodextrin nanosponges (SN-AXCDNS) were designed to evaluate antitumor activity against breast cancer. Therefore, SN-AXCDNS were prepared by using cross-linker melt method and characterized by physicochemical and pharmacological parameters. Results: Hydrodynamic size, zeta potential and entrapment efficiency (EE%) were estimated as 226 ± 4 nm, -29.15 ± 5.71 mV and 93%, respectively. Surface morphology of nanocomposites showed spherical, smooth, and porous form. Antitumor pharmacological characterization showed that SN loaded nanosponge demonstrated higher cytotoxicity (22.67 ± 6.11 µg/mL), by inducing DNA damage as compared to void SN extract. Flow cytometry analysis reported that encapsulated extract promoted cell cycle arrest at sub-G1 (9.51%). Moreover, in vivo analysis demonstrates the reduction in tumor weight and 85% survival chances in nanosponge treated mice featuring its effectiveness. In addition, in silico analysis revealed that ß-cyclodextrin potentially inhibits MELK in breast cancer cell lines (B.E = -10.1 Kcal/mol). Conclusion: Therefore, findings of current study elucidated the therapeutic potential of ß-cyclodextrin based nanosponges to be an alternative approach regarding the delivery and solubilization of antitumor drugs.

Sulconazole-Loaded Solid Lipid Nanoparticles for Enhanced Antifungal Activity: In Vitro and In Vivo Approach.

Solid lipid nanoparticles (SLNs) have the advantages of a cell-specific delivery and sustained release of hydrophobic drugs that can be exploited against infectious diseases. The topical delivery of hydrophobic drugs needs pharmaceutical strategies to enhance drug permeation, which is a challenge faced by conventional formulations containing a drug suspended in gel, creams or ointments. We report the fabrication and optimization of SLNs with sulconazole (SCZ) as a model hydrophobic drug and then a formulation of an SLN-based topical gel against fungal infections. The SLNs were optimized through excipients of glyceryl monostearate and Phospholipon® 90 H as lipids and tween 20 as a surfactant for its size, drug entrapment and sustained release and resistance against aggregation. The SCZ-SLNs were physically characterized for their particle size (89.81 ± 2.64), polydispersity index (0.311 ± 0.07), zeta potential (-26.98 ± 1.19) and encapsulation efficiency (86.52 ± 0.53). The SCZ-SLNs showed sustained release of 85.29% drug at the 12 h timepoint. The TEM results demonstrated spherical morphology, while DSC, XRD and FTIR showed the compatibility of the drug inside SLNs. SCZ-SLNs were incorporated into a gel using carbopol and were further optimized for their rheological behavior, pH, homogeneity and spreadability on the skin. The antifungal activity against Candida albicans and Trichophyton rubrum was increased in comparison to a SCZ carbopol-based gel. In vivo antifungal activity in rabbits presented faster healing of skin fungal infections. The histopathological examination of the treated skin from rabbits presented restoration of the dermal architecture. In summary, the approach of formulating SLNs into a topical gel presented an advantageous drug delivery system against mycosis.

Tioconazole-Loaded Transethosomal Gel Using Box-Behnken Design for Topical Applications: In Vitro, In Vivo, and Molecular Docking Approaches.

Tioconazole (TCZ) is a broad-spectrum fungicidal BCS class II drug with reported activity against Candida albicans, dermatophytes, and certain Staphylococci bacteria. We report the use of TCZ-loaded transethosomes (TEs) to overcome the skin's barrier function. TCZ-loaded TEs were fabricated by using a cold method with slight modification. Box-Behnken composite design was utilized to investigate the effect of independent variables. The fabricated TEs were assessed with various physicochemical characterizations. The optimized formulation of TCZ-loaded TEs was incorporated into gel and evaluated for pH, conductivity, drug content, spreadability, rheology, in vitro permeation, ex vivo permeation, and in vitro and in vivo antifungal activity. The fabricated TCZ-loaded TEs had a % EE of 60.56 to 86.13, with particle sizes ranging from 219.1 to 757.1 nm. The SEM images showed spherically shaped vesicles. The % drug permeation was between 77.01 and 92.03. The kinetic analysis of all release profiles followed Higuchi's diffusion model. The FTIR, DSC, and XRD analysis showed no significant chemical interactions between the drug and excipients. A significantly higher antifungal activity was observed for TCZ-loaded transethosomal gel in comparison to the control. The in vivo antifungal study on albino rats indicated that TCZ-loaded transethosomal gel showed a comparable therapeutic effect in comparison to the market brand Canesten®. Molecular docking demonstrated that the TCZ in the TE composition was surrounded by hydrophobic excipients with increased overall hydrophobicity and better permeation. Therefore, TCZ in the form of transethosomal gel can serve as an effective drug delivery system, having the ability to penetrate the skin and overcome the stratum corneum barrier with improved efficacy.

Fabrication and Evaluation of Anticancer Potential of Eugenol Incorporated Chitosan-Silver Nanocomposites: In Vitro, In Vivo, and In Silico Studies.

The expanding global cancer burden necessitates a comprehensive strategy to promote possible therapeutic interventions. Nanomedicine is a cutting-edge approach for treating cancer with minimal adverse effects. In the present study, chitosan-silver nanoparticles (ChAgNPs) containing Eugenol (EGN) were synthesized and evaluated for their anticancer activity against breast cancer cells (MCF-7). The physical, pharmacological, and molecular docking studies were used to characterize these nanoparticles. EGN had been effectively entrapped into hybrid NPs (84 ± 7%). The EGN-ChAgNPs had a diameter of 128 ± 14 nm, a PDI of 0.472 ± 0.118, and a zeta potential of 30.58 ± 6.92 mV. Anticancer activity was measured in vitro using an SRB assay, and the findings revealed that EGN-ChAgNPs demonstrated stronger anticancer activity against MCF-7 cells (IC50 = 14.87 ± 5.34 µg/ml) than pure EGN (30.72 ± 4.91 µg/ml). To support initial cytotoxicity findings, advanced procedures such as cell cycle analysis and genotoxicity were performed. Tumor weight reduction and survival rate were determined using different groups of mice. Both survival rates and tumor weight reduction were higher in the EGN-ChAgNPs (12.5 mg/kg) treated group than in the pure EGN treated group. Based on protein-ligand interactions, it might be proposed that eugenol had a favorable interaction with Aurora Kinase A. It was observed that C9 had the highest HYDE score of any sample, measuring at -6.8 kJ/mol. These results, in conjunction with physical and pharmacological evaluations, implies that EGN-ChAgNPs may be a suitable drug delivery method for treating breast cancer in a safe and efficient way.

Fabrication and Evaluation of Voriconazole Loaded Transethosomal Gel for Enhanced Antifungal and Antileishmanial Activity.

Voriconazole (VRC) is a broad-spectrum antifungal agent belonging to BCS class II (biopharmaceutical classification system). Despite many efforts to enhance its solubility, this primary issue still remains challenging for formulation scientists. Transethosomes (TELs) are one of the potential innovative nano-carriers for improving the solubility and permeation of poorly soluble and permeable drugs. We herein report voriconazole-loaded transethosomes (VRCT) fabricated by the cold method and followed by their incorporation into carbopol 940 as a gel. The prepared VRCT were evaluated for % yield, % entrapment efficiency (EE), surface morphology, possible chemical interaction, particle size, zeta potential, and polydispersity index (PDI). The optimized formulation had a particle size of 228.2 nm, a zeta potential of -26.5 mV, and a PDI of 0.45 with enhanced % EE. Rheology, spreadability, extrudability, in vitro release, skin permeation, molecular docking, antifungal, and antileishmanial activity were also assessed for VRCT and VRC loaded transethosomal gel (VTEG). Ex-vivo permeation using rat skin depicted a transdermal flux of 22.8 µg/cm2/h with enhanced efficiency up to 4-fold. A two-fold reduction in inhibitory as well as fungicidal concentration was observed against various fungal strains by VRCT and VTEG besides similar results against L-donovani. The development of transethosomal formulation can serve as an efficient drug delivery system through a topical route with enhanced efficacy and better patient compliance.

Fenugreek seed mucilage grafted poly methacrylate pH-responsive hydrogel: A promising tool to enhance the oral bioavailability of methotrexate.

This study aimed to develop the Fenugreek seed mucilage-based pH-responsive hydrogel system in order to improve the oral bioavailability of methotrexate (MTX). Fenugreek seed mucilage (FSM) was extracted from Trigonella foenum-graecum seeds. F1-F9 formulations of pH-responsive hydrogels were prepared using various FSM ratios, methacrylic acid (MAA), and methylene bis acrylamide (MBA) via free radical polymerization technique. Swelling behavior and in vitro drug release studies of prepared hydrogels were evaluated. Toxicity studies of prepared hydrogels were performed on normal cells and on Wistar rats (n = 6). Moreover, in vivo pharmacokinetics parameters were studied on albino rabbits. Hydrogels formation was confirmed by FTIR analysis, thermal analysis and SEM studies. The maximum swelling of hydrogel was found to be 384.7% at pH 7.4. MTX-loaded hydrogel showed the controlled release of MTX up to 24 h following Super Case II transport. Prepared hydrogels exhibited no toxicity in normal cells as well as in experimental subjects. MTX loaded hydrogels exhibited less inhibition compared to free MTX on Hela cells. In Vivo studies revealed 7.5-fold improved oral bioavailability of MTX with higher Cmax (928 ng/mL). These results indicate that the pH-responsive hydrogel system based on FSM is a promising tool for the controlled delivery of MTX.

Preparation, Characterization, and Pharmacological Investigation of Withaferin-A Loaded Nanosponges for Cancer Therapy; In Vitro, In Vivo and Molecular Docking Studies.

The rapidly growing global burden of cancer poses a major challenge to public health and demands a robust approach to access promising anticancer therapeutics. In parallel, nanotechnology approaches with various pharmacological properties offer efficacious clinical outcomes. The use of new artificial variants of nanosponges (NS) as a transporter of chemotherapeutic drugs to target cells has emerged as a very promising tool. Therefore, in this research, ethylcellulose (EC) NS were prepared using the ultrasonication assisted-emulsion solvent evaporation technique. Withaferin-A (WFA), an active ingredient in Withania somnifera, has been implanted into the nanospongic framework with enhanced anticancer properties. Inside the polymeric structure, WFA was efficiently entrapped (85 ± 11%). The drug (WFA) was found to be stable within polymeric nanosponges, as demonstrated by Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC) studies. The WFA-NS had a diameter of 117 ± 4 nm and zeta potential of -39.02 ± 5.71 mV with a polydispersity index (PDI) of 0.419 ± 0.073. In addition, scanning electron microscopy (SEM) revealed the porous surface texture of WFA-NS. In vitro anticancer activity (SRB assay) results showed that WFA-NS exhibited almost twice the anticancer efficacy against MCF-7 cells (IC50 = 1.57 ± 0.091 µM), as quantified by flow cytometry and comet tests. Moreover, fluorescence microscopy with DAPI staining and analysis of DNA fragmentation revealed apoptosis as a mechanism of cancer cell death. The anticancer activity of WFA-NS was further determined in vivo and results were compared to cisplatin. The anticancer activity of WFA-NS was further investigated in vivo, and the data were consistent to those obtained with cisplatin. At Day 10, WFA-NS (10 mg/kg) significantly reduced tumour volume to 72 ± 6%, which was comparable to cisplatin (10 mg/kg), which reduced tumour volume to 78 ± 8%. Finally, the outcomes of molecular modeling (in silico) also suggested that WFA established a stable connection with nanosponges, generating persistent hydrophobic contacts (polar and nonpolar) and helping with the attractive delayed-release features of the formulation. Collectively, all the findings support the use of WFA in nanosponges as a prototype for cancer treatment, and opened up new avenues for increasing the efficacy of natural product-derived medications.

Fabrication and Biological Assessment of Antidiabetic α-Mangostin Loaded Nanosponges: In Vitro, In Vivo, and In Silico Studies.

Type 2 diabetes mellitus has been a major health issue with increasing morbidity and mortality due to macrovascular and microvascular complications. The urgent need for improved methods to control hyperglycemic complications reiterates the development of innovative preventive and therapeutic treatment strategies. In this perspective, xanthone compounds in the pericarp of the mangosteen fruit, especially α-mangostin (MGN), have been recognized to restore damaged pancreatic ß-cells for optimal insulin release. Therefore, taking advantage of the robust use of nanotechnology for targeted drug delivery, we herein report the preparation of MGN loaded nanosponges for anti-diabetic therapeutic applications. The nanosponges were prepared by quasi-emulsion solvent evaporation method. Physico-chemical characterization of formulated nanosponges with satisfactory outcomes was performed with Fourier transform infra-red (FTIR) spectroscopy, differential scanning calorimetry (DSC), and scanning electron microscopy (SEM). Zeta potential, hydrodynamic diameter, entrapment efficiency, drug release properties, and stability studies at stress conditions were also tested. Molecular docking analysis revealed significant interactions of α-glucosidase and MGN in a protein-ligand complex. The maximum inhibition by nanosponges against α-glucosidase was observed to be 0.9352 ± 0.0856 µM, 3.11-fold higher than acarbose. In vivo studies were conducted on diabetic rats and plasma glucose levels were estimated by HPLC. Collectively, our findings suggest that MGN-loaded nanosponges may be beneficial in the treatment of diabetes since they prolong the antidiabetic response in plasma and improve patient compliance by slowly releasing MGN and requiring less frequent doses, respectively.

Erupt of malaria, dengue and chikungunya in Pakistan: Recent insights about prevalence, diagnosis and treatment.

Malaria, dengue and chikungunya are the most rampant mosquito-borne infections predominantly in Pakistan. They pose a serious threat and cause a havoc for the victims owing to the life threatening signs and symptoms marked with elevated morbidity and mortality rate. It seems hard to discriminate due to common indications, consequently, deserves appropriate diagnosis prior elevated toll of death. Present article encompasses depth insights about their prevalence, diagnosis and clinical manifestation if erupt in the pandemic. However, host-vector-host cycle is the root cause of transmission and diverse mosquito species confer dissimilar infections. Indeed these infections are seasonal but other factors like flood, open irrigation channels, immense agricultural land, rich fauna and water reservoirs can't be overlooked. Dire need was felt to acknowledge and aware the public about local transmission, vector control, entomologic, research resources, diagnosis and advancement in healthcare system to alleviate them absolutely in future.

Quinoline containing chalcone derivatives as cholinesterase inhibitors and their in silico modeling studies.

Cholinesterases (ChEs) play a vital role in regulating cholinergic transmission. Inhibition of ChEs is thought to be an emerging and useful therapeutic target for neurodegenerative disorders through restoration of acetylcholine (ACh) levels in the brain (e.g. Alzheimer's disease). To increase the chemical diversity of cholinesterase inhibitors, a series of quinoline chalcones derivatives were tested against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) isoenzymes. All tested compounds (4a-1; 5a-s) exhibited inhibitory activities against AChE and BChE to a considerable extent. Molecular docking studies were performed by using homology models on both AChE and BChE isoenzymes with the aim of exploring probable binding modes of the most potent inhibitor. In order to evaluate drug likeness of newly tested molecules, we carried out in-silico ADME evaluation. All compounds displayed favourable ADME findings which predict good oral bioavailability of these derivatives. Due to an excellent ADME profile the tested compounds were predicted to be safer which can be considered as novel cholinesterase inhibitors.

New cholinesterase inhibitors for Alzheimer's disease: Structure activity relationship, kinetics and molecular docking studies of 1-butanoyl-3-arylthiourea derivatives.

Highly progressive neurodegenerative disorder generally known as Alzheimer's disease (AD), is a type of dementia, which is very common in elderly. The most common symptoms may include loss of memory along with disturbed behavioral and cognitive functions. Until now, only 4 cholinesterase (ChE) inhibitors are approved by FDA for symptomatic treatment of AD. Aroyl thiourea derivatives are well known bioactive organic molecules containing carbonyl and thiocarbonyl functional groups. Here, total 14 different thiourea derivatives (3a-3n) were synthesized and characterized by NMR, FTIR and X-ray crystallographic techniques. The synthesized compounds displayed varying inhibition activities on both acetylcholineterase (AChE) and butyrylcholinesterase (BuChE) enzymes. Among all compounds, 3b and 3e were potent inhibitors of AChE (IC50 ±â€¯SEM = 8.92 ±â€¯1.03 µM) and BuChE (IC50 ±â€¯SEM = 6.96 ±â€¯0.961 µM) respectively. Enzyme kinetic studies showed that 3b exhibited uncompetitive binding with AChE while 3e demonstrated a mixed inhibition of BuChE. Molecular docking studies on AChE showed that 3b got binding interaction with Trp86 and Tyr337 while 3e showed binding affinity with Trp82 and His438 when docked with BuChE. The obtained results indicated that these thiourea derivatives could be considered as potential candidates to treat AD.

Synthesis of novel (E)-1-(2-(2-(4(dimethylamino) benzylidene) hydrazinyl)-4-methylthiazol-5-yl)ethanone derivatives as ecto-5'-nucleotidase inhibitors.

Ecto-5'-nucleotidase (e5'NT), a membrane-bound enzyme and an essential member of ecto-nucleotidases which regulates extracellular purinergic signalling. Their upregulation results in various disease conditions, for example, inflammation, hypoxia and cancer. Therefore, efforts have been made to synthesize potent and selective inhibitors of e5'NT. Here we have synthesized, characterized and evaluated six thiazole derivatives (3a-3f) as potent e5'NT inhibitors. Among all derivatives, the compound (E)-1-(4-methyl-2-(2-(pyridin-3-ylmethylene)hydrazinyl) thiazol-5-yl)ethanone (3a) exhibited maximum inhibition towards both human and rat enzymes. However, their potency against h-e5'NT was 24-fold higher than r-e5'NT. Only two compounds exhibited inhibitory behaviour towards r-e5'NT. The molecular structures of these derivatives were confirmed with the help of solid-state characterization through NMR (1H and 13C), FTIR and elemental analysis. Additionally, molecular docking was also implemented to explain putative bonding interaction between the active site of an enzyme and potent inhibitors.

Antidiabetic potential of polyoxotungstates: in vitro and in vivo studies.

Diabetes mellitus is a chronic metabolic disorder continuously affecting people all over the world. A common way to treat diabetes mellitus is to limit the conversion of carbohydrates into glucose which is mediated by glucosidase enzymes. Diabetes mellitus is also famous for its life-threatening microvascular (retinopathy, neuropathy and nephropathy) and macrovascular (atherosclerosis) complications. Aldose reductases present in eye lens (ALR1) and kidney (ALR2) are responsible for microvascular complications. The production of advanced glycation end products (AGEs) is involved in the development of atherosclerosis. The present work was aimed at the synthesis and in vitro/in vivo evaluation of different polyoxotungstates against glucosidases (α- and ß), aldose reductases (ALR1 and ALR2) and AGEs to discover a new treatment which may limit the complications associated with diabetes mellitus. The polyanion [P6W18O79](20-) was found to be the most potent inhibitor of α-glucosidase (IC50 = 1.33 ± 0.41 µM), ALR1 (IC50 = 0.4 ± 0.009 µM) and ALR2 (IC50 = 0.38 ± 0.02 µM). Animal studies showed that the polyanion [H2W12O40](6-) was very effective in reducing the blood glucose level to 84.25 ± 5.07 mg dL(-1) when compared with standard antidiabetic drug glibenclamide (150.62 ± 9.35 mg dL(-1)) measured after maximum 8 h of dose administration. The data obtained from in vitro and in vivo experiments confirm that [P6W18O79](20-) and [H2W12O40](6-) could be used as a new treatment of diabetes mellitus.

A novel example of double 6-exo-trig heterocyclization: nitrile conversion to new anticancer active (HeLa cells) primary amine ionic liquids.

Conversion of nitriles under mild conditions leads to a new class of primary amines, including room temperature ionic liquids, acting as efficient anticancer agents.

Cytotoxicity and enzyme inhibition studies of polyoxometalates and their chitosan nanoassemblies.

Polyoxometalates (POMs) have become very significant in biomedical research for their structural diversity which renders them highly active against bacterial, viral and cancer diseases. In this study three different POMs were synthesized and nanoassemblies were made with chitosan (CTS), a natural biodegradable polymer with excellent drug carrier properties. The compounds were tested on two isoenzymes of alkaline phosphatases including tissue specific calf intestine alkaline phosphatase (CIAP) and tissue non-specific alkaline phosphatase (TNAP). Compound [TeW6O24]6- (TeW6) showed the highest activity (45.4 ± 11.3 nM) among tested compounds against TNAP. Similarly, chitosan-[TeW6O24]6- (CTS-TeW6) was proved to be a potent inhibitor of CIAP with Ki value of 22 ± 7 nM. A comparative study was made to evaluate their cytotoxic potential against HeLa cells. Among all tested compounds, Chitosan-[NaP5W30O110]14- (CTS-P5W30) has showed higher percent cytotoxicity (88 ± 10%) at 10 µM when compared with the standard anticancer drug vincristine (72 ± 7%). The study revealed that selected POMs proved excellent anticancer potential and were equally effective against alkaline phosphatase enzyme, an increased level of which may indicate cancer metastasis.