Novel quinazolines bearing 1,3,4-thiadiazole-aryl urea derivative as anticancer agents: design, synthesis, molecular docking, DFT and bioactivity evaluations.

A novel series of 1-(5-((6-nitroquinazoline-4-yl)thio)-1,3,4-thiadiazol-2-yl)-3-phenylurea derivatives 8 were designed and synthesized to evaluate their cytotoxic potencies. The structures of these obtained compounds were thoroughly characterized by IR, 1H, and 13C NMR, MASS spectroscopy and elemental analysis methods. Additionally, their in vitro anticancer activities were investigated using the MTT assay against A549 (human lung cancer), MDA-MB231 (human triple-negative breast cancer), and MCF7 (human hormone-dependent breast cancer). Etoposide was used as a reference marketed drug for comparison. Among the compounds tested, compounds 8b and 8c demonstrated acceptable antiproliferative activity, particularly against MCF7 cells. Considering the potential VEGFR-2 inhibitor potency of these compounds, a molecular docking study was performed for the most potent compound, 8c, to determine its probable interactions. Furthermore, computational investigations, including molecular dynamics, frontier molecular orbital analysis, Fukui reactivity descriptor, electrostatic potential surface, and in silico ADME evaluation for all compounds were performed to illustrate the structure-activity relationship (SAR).

A Mesoporous Magnetic Fe3O4/BioMOF-13 with a Core/Shell Nanostructure for Targeted Delivery of Doxorubicin to Breast Cancer Cells.

In the current project, magnetic Bio-MOF-13 was used as an efficient carrier for the targeted delivery and controlled release of doxorubicin (DOX) to MDA-MB-231 cells. Magnetic Bio-MOF-13 was prepared by two strategies and compared to determine the optimal state of the structure. In the first path, Bio-MOF-13 was grown in situ on the surface of Fe3O4 nanoparticles (core/shell structure), while in the second method, the two presynthesized materials were mixed together (surface composite). Core/shell structure, among prepared nanocomposites, was chosen for biological evaluation due to its favorable structural features like a high accessible surface area and pore volume. Also, it is highly advantageous for drug release due to its ability to selectively release DOX in the acidic pH of breast cancer cells, while preventing any premature release in the neutral pH of the blood. Drug release from the carrier structure is precisely controlled not only by pH but also by an external magnetic field, guaranteeing accurate drug delivery at the intended location. Confocal microscopy and flow cytometry assay clearly confirms the increase in drug concentration in the MDA-MB-231 cell line after external magnet applying. This point, along with the low toxicity of the carrier components, makes it a suitable candidate for injectable medicine. According to MTT results, the percentage of viable MDA-MB-231 cells after treatment with 10 µL of DOX@Fe3O4/Bio-MOF-13 core/shell composite in different concentrations, in the presence and absence of magnetic field is 0.87 ± 0.25 and 2.07 ± 0.15, respectively. As a result, the DOX@Fe3O4/Bio-MOF-13 core/shell composite was performed and approved for targeted drug delivery and magnetic field-assisted controlled release of DOX to the MDA-MB-231 cell line.

Imidazopyridine-based kinase inhibitors as potential anticancer agents: A review.

Considering the fundamental role of protein kinases in the mechanism of protein phosphorylation in critical cellular processes, their dysregulation, especially in cancers, has underscored their therapeutic relevance. Imidazopyridines represent versatile scaffolds found in abundant bioactive compounds. Given their structural features, imidazopyridines have possessed pivotal potency to interact with different protein kinases, inspiring researchers to carry out numerous structural variations. In this comprehensive review, we encompass an extensive survey of the design and biological evaluations of imidazopyridine-based small molecules as potential agents targeting diverse kinases for anticancer applications. We describe the structural elements critical to inhibitory potency, elucidating their key structure-activity relationships (SAR) and mode of actions, where available. We classify these compounds into two groups: Serine/threonine and Tyrosine inhibitors. By highlighting the promising role of imidazopyridines in kinase inhibition, we aim to facilitate the design and development of more effective, targeted compounds for cancer treatment.

Improving biomass and carbohydrate production of microalgae in the rotating cultivation system on natural carriers.

Biofilm-based algal technologies have gained popularity due to higher biomass productivity, efficient harvesting, and water-saving over suspended growth systems. A rotating attached system was designed to assess the biofilm-forming capacity of different isolated microalgal strains from the Persian Gulf. Four microalgal strains, including two Chlorella sp., one Picochlorum sp. and one filamentous cyanobacterium Desmonostoc sp. were cultivated on four carriers: jute, cotton, yarn and nylon. The carriers' physicochemical surface characteristics and attachment effects, like contact angle, were investigated. The incorporated biomass and exopolysaccharides (EPS) content in the suspended and biofilm system was calculated and compared. The results showed that the cyanobacterium strain had the biofilm formation capability on both jute and cotton in the attached cultivation system. Under the same culture conditions, the biomass productivity on jute and cotton carriers was significantly higher (4.76 and 3.61 g m- 2 respectively) than the growth in aqueous suspension (1.19 g m- 2 d- 1). The greatest incorporated exopolysaccharides amount was observed on jute (43.62 ± 4.47%) and the lowest amount was obtained from the growth on positive charge yarn (18.62 ± 1.88%). This study showed that in comparison with planktonic growth, the colonization of cyanobacterial cells and subsequent production of extracellular matrix and biofilm formation can lead to increased biomass production.

Enhanced production of bioactive compounds from marine microalgae Tetraselmis tetrathele under salinity and light stresses: A two-stage cultivation strategy.

This study leveraged the salinity and light intensity stresses during the stationary phase for enhancing the pigment contents and antioxidant capacity of Tetraselmis tetrathele. The highest pigments content was obtained in cultures under salinity stress (40 g L-1) illuminated using fluorescent light. Furthermore, the best inhibitory concentration (IC50) for scavenging the 2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radicals was found as 79.53 µg mL-1 in ethanol extract and cultures under red LED light stress (300 µmol m-2 s-1). The highest antioxidant capacity in a ferric-reducing antioxidant power (FRAP) assay (1,778.6 µM Fe+2) was found in ethanol extract and cultures under salinity stress illuminated using fluorescent light. Maximum scavenging of the 2.2-diphenyl-1-picrylhydrazyl (DPPH) radical was found in ethyl acetate extracts under light and salinity stresses. These results indicated that abiotic stresses could enhance the pigment and antioxidant components of T. tetrathele, which are value-added compounds in the pharmaceutical, cosmetic, and food industries.

Thioquinoline derivatives conjugated to thiosemicarbazide as potent tyrosinase inhibitors with anti-melanogenesis properties.

In the present study, a series of aryl-substituted thioqunoline conjugated to thiosemicarbazide were rationally designed and synthesized. The formation of target compounds was confirmed by spectral characterization techniques such as IR, 1H-NMR, 13C-NMR, ESI-MS, and elemental analysis. Among the synthesized derivatives, compound 10g bearing para-chlorophenyl moiety was proved to be the most potent tyrosinase inhibitor with an IC50 value of 25.75 ± 0.19 µM. Compound 10g as the most potent derivative exhibited a noncompetitive inhibition pattern against tyrosinase in the kinetic study. Furthermore, the in silico cavity detection, as well as the molecular docking assessments, were performed to follow the behavior of 10g within the proposed binding site. Besides, the toxicity of 10g and its potency to reduce the melanin content on A375 cell lines were also measured. Consequently, aryl-substituted thioqunolines conjugated to thiosemicarbazide might be a promising candidate in the cosmetics, medicine, and food industry as tyrosinase inhibitors.

Overcoming the non-kinetic activity of EGFR1 using multi-functionalized mesoporous silica nanocarrier for in vitro delivery of siRNA.

Triple-negative breast cancer (TNBC) does not respond to HER2-targeted and hormone-based medicines. Epidermal growth factor receptor 1 (EGFR1) is commonly overexpressed in up to 70% of TNBC cases, so targeting cancer cells via this receptor could emerge as a favored modality for TNBC therapy due to its target specificity. The development of mesoporous silica nanoparticles (MSNs) as carriers for siRNAs remains a rapidly growing area of research. For this purpose, a multi-functionalized KIT-6 containing the guanidinium ionic liquid (GuIL), PEI and PEGylated folic acid (FA-PEG) was designed. Accordingly, KIT-6 was fabricated and modified with FA-PEG and PEI polymers attached on the surface and the GuIL placed in the mesopores. Subsequent to confirming the structure of this multi-functionalized KIT-6- based nanocarrier using TEM, SEM, AFM, BET, BJH, DLS and Zeta Potential, it was investigated for uploading and transferring the anti-EGFR1 siRNAs to the MD-MBA-231 cell line. The rate of cellular uptake, cellular localization and endolysosomal escape was evaluated based on the fluorescent intensity of FAM-labelled siRNA using flowcytometry analysis and confocal laser scanning microscopy (CLSM). The 64% cellular uptake after 4 h incubation, clearly suggested the successful delivery of siRNA into the cells and, CLSM demonstrated that siRNA@[FA-PEGylated/PEI@GuIL@KIT-6] may escape endosomal entrapment after 6 h incubation. Using qPCR, quantitative evaluation of EGFR1 gene expression, a knockdown of 82% was found, which resulted in a functional change in the expression of EGFR1 targets. Co-treatment of chemotherapy drug "carboplatin" in combination with siRNA@[FA-PEGylated/PEI@GuIL@KIT-6] exhibited a remarkable cytotoxic effect in comparison to carboplatin alone.

Untargeted Metabolomics Analysis of Crocus cancellatus subsp. damascenus (Herb.) B. Mathew Stigmas and Their Anticarcinogenic Effect on Breast Cancer Cells.

Safranal, crocin, crocetin, and picrocrocin are major known compounds in the stigma extract of Crocus sativus with various medicinal properties. Crocus cancellatus is another Crocus species that grows extensively in Iran's various regions, such as the Kurdistan province. The predominant metabolites and biological properties of C. cancellatus have not yet been investigated. The ingredients of the stigma ethanol extract of C. cancellatus were investigated using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography with tandem mass spectrometry (LC-MS). The ROIMCR approach was performed to analyze the LC-MS full scan data sets. This method searches the MS regions of interest (ROI) data in the m/z domain and analyses the results using the multivariate curve-resolution alternating least squares (MCR-ALS) chemometrics technique for simultaneous resolution of two extracts. Also, the antiproliferative properties of C. cancellatus against MDA-MB-231 and MCF-7 cancer cells were examined by MTT, dual acridine orange/ethidium bromide test, Annexin V-FITC/PI, and zymography. The GC-MS and LC-MS untargeted metabolomics data analysis of the extract indicated the presence of cytotoxic agents including safranal, crocin, picrocrocin, and crocetin in the stigma ethanol extract of C. cancellatus. Biological tests showed that the viability of MDA-MB-231 and MCF-7 cancer cells is decreased following C. cancellatus treatment in a time- and dose-dependent way in both monolayer and 3D cell cultures. The MCF-7 cell spheroids had greater resistance to the cytotoxic activity of the extract in 3D cell culture than the MDA-MB-231 cell spheroids. The morphological changes of the cells treated with C. cancellatus stigmas extract were indicative of apoptosis. Zymography analysis revealed a similar trend of matrix metallopeptidase-2 (MMP-2) and matrix metallopeptidase-9 (MMP-9) activity in the treated cells with C. cancellatus extract in comparison with doxorubicin treatment as a positive control. The findings of this research indicate that the ethanolic extract of C. cancellatus stigmas was a good source of bioactive metabolites with anticancer activity.

A Novel Salt-Bridge Electroflocculation Technology for Harvesting Microalgae.

Microalgae biomass, as a promising alternative feedstock, can be refined into biodiesel, pharmaceutical, and food productions. However, the harvesting process for quality biomass still remains a main bottleneck due to its high energy demand. In this study, a novel technique integrating alkali-induced flocculation and electrolysis, named salt-bridge electroflocculation (SBEF) with non-sacrificial carbon electrodes is developed to promote recovery efficiency and cost savings. The results show that the energy consumption decreased to 1.50 Wh/g biomass with a high harvesting efficiency of 90.4% under 300 mA in 45 min. The mean particle size of algae flocs increased 3.85-fold from 2.75 to 10.59 µm, which was convenient to the follow-up processing. Another major advantage of this method is that the salt-bridge firmly prevented cells being destroyed by the anode's oxidation and did not bring any external contaminants to algal biomass and flocculated medium, which conquered the technical defects in electro-flocculation. The proposed SBEF technology could be used as a low cost process for efficient microalgae harvest with high quality biomass.

New insights into the inhibitory roles and mechanisms of D-amino acids in bacterial biofilms in medicine, industry, and agriculture.

Biofilms are complex aggregates of microbes that are tightly protected by an extracellular matrix (ECM) and may attach to a surface or adhere together. A higher persistence of bacteria on biofilms makes them resistant not only to harsh conditions but also to various antibiotics which led to the emergence of problems in different applications. Recently, it has been discovered that many bacteria produce and release various D-amino acids (D-AAs) to inhibit biofilm formation, which made a great deal of interest in research into the control of bacterial biofilms in diverse fields, such as human health, industrial settings, and medical devices. D-AAs have various mechanisms to inhibit bacterial biofilms such as: (i) interfering with protein synthesis (ii) Inhibition of extracellular polymeric materials (EPS) productions (protein, eDNA, and polysaccharide) (iii) Inhibition of quorum sensing (autoinducers), and (iv) interfere with peptidoglycan synthesis, these various modes of action, enables these small molecules to inhibit both Gram-negative and Gram-positive bacterial biofilms. Since most biofilms are multi-species, D-AAs in combination with other antimicrobial agents are good choices to combat a variety of bacterial biofilms without displaying toxicity on human cells. This review article addressed the role of D-AAs in controlling several bacterial biofilms and described the possible or definite mechanisms involved in this process.

In vitro cell-based models of drug-induced hepatotoxicity screening: progress and limitation.

Drug-induced liver injury (DILI) is one of the major causes of post-approval withdrawal of therapeutics. As a result, there is an increasing need for accurate predictive in vitro assays that reliably detect hepatotoxic drug candidates while reducing drug discovery time, costs, and the number of animal experiments. In vitro hepatocyte-based research has led to an improved comprehension of the underlying mechanisms of chemical toxicity and can assist the prioritization of therapeutic choices with low hepatotoxicity risk. Therefore, several in vitro systems have been generated over the last few decades. This review aims to comprehensively present the development and validation of two-dimensional (2D) and three-dimensional (3D) culture approaches on hepatotoxicity screening of compounds and highlight the main factors affecting predictive power of experiments. To this end, we first summarize some of the recognized hepatotoxicity mechanisms and related assays used to appraise DILI mechanisms and then discuss the challenges and limitations of in vitro models.

Characterization, antioxidant and anticoagulant properties of exopolysaccharide from marine microalgae.

The sulfated exopolysaccharide extracted from marine microalgae attracted considerable attention from both the nutraceutical and pharmaceutical industries. In the present study biomass of five marine microalgae were screened to find strains with high capacity for the production of sulfated exopolysaccharides. The anticoagulant and antioxidant activities of extracted sulfated polysaccharides were evaluated using activated partial thromboplastin time (aPTT), prothrombin time (PT), DPPH and ABTS assays, respectively. The sulfated polysaccharides extracted from Picochlorum sp. showed a strong DPPH scavenging effect with 85% antioxidant activity. The sulfated polysaccharides of Chlorella sorokiniana, Chlorella sp. (L2) and Chlorella sp. (D1) scavenged more than 90% of the ABTS radicals. However, the sulfated polysaccharide extracted from Chlorella sorokiniana, and Chlorella sp. (N4) showed anticoagulant properties. The dual anticoagulant-antioxidant activities in Chlorella sorokiniana could be explained by the combination of various factors including sulfate content and their binding site, monosaccharide residue and glycoside bond which are involved in the polysaccharide's bioactivity.

Synthesis and biological activity profile of novel triazole/quinoline hybrids.

Based on the significant and diverse pharmacophore features of triazole ring and considering the potent antimicrobial properties of quinoline scaffold, a novel series of 1,2,3-triazole-based polyaromatic compounds containing chloroquinoline moiety were synthesized through a well-established synthetic methodology, named click chemistry. The structure of the synthetic compounds was characterized by various spectroscopic methods. The final products of triazole/quinoline hybrids and ((prop-2-yn-1-yloxy)methyl)benzene intermediates were screened for their antibacterial (Staphylococcus aureus, Escherichia coli, Shigella flexneri, and Salmonella enterica), antifungal (Candida albicans, Saccharomyces cerevisiae, and Aspergillus fumigatus), and cytotoxic activities. The best antifungal compounds exhibited minimum inhibitory concentration (MIC), in the range of 0.35-0.63 µM, against S. cerevisiae without any cytotoxic effect. These compounds can be selected as the potential candidates for treating invasive fungal infections caused by S. cerevisiae, after further investigation. Preliminary in silico ADME studies also predicted the favorable pharmacokinetic attributes of most compounds.

Butylated hydroxyl-toluene, 2,4-Di-tert-butylphenol, and phytol of Chlorella sp. protect the PC12 cell line against H2O2-induced neurotoxicity.

Oxidative stress is considered the main cause of cellular damage in a number of neurodegenerative disorders. One suitable ways to prevent cell damage is the use of the exogenous antioxidant capacity of natural products, such as microalgae. In the present study, four microalgae extracts, isolated from the Persian Gulf, were screened to analyze their potential antioxidant activity and free radical scavenging using ABTS, DPPH, and FRAP methods. The methanolic extracts (D1M) of green microalgae derived from Chlorella sp. exhibited potent free radical scavenging activity. In order to characterize microalgae species, microscopic observations and analysis of the expression of 18S rRNA were performed. The antioxidant and neuroprotective effects of D1M on H2O2-induced toxicity in PC12 cells were investigated. The results demonstrated that D1M significantly decreased the release of nitric oxide (NO), formation of intracellular reactive oxygen species (ROS), and the level of malondialdehyde (MDA), whereas it enhanced the content of glutathione (GSH), and activity of heme oxygenase 1 (HO-1), NAD(P)H: quinone oxidoreductase 1 (NQO1), and catalase (CAT) in PC12 cells exposed to H2O2. The pretreatment of D1M improved cell viability as measured by the MTT assay and invert microscopy, reduced cell apoptosis as examined by flow cytometry analysis, increased mitochondrial membrane potential (MMP), and diminished caspase-3 activity. The GC/MS analysis revealed that D1M ingredients have powerful antioxidant and anti-inflammatory compounds, such as butylated hydroxytoluene (BHT), 2,4-di-tert-butyl-phenol (2,4-DTBP), and phytol. These results suggested that Chlorella sp. extracts have strong potential to be applied as neuroprotective agents, for the treatment of neurodegenerative disorders.

Synthesis and evaluation of novel arylisoxazoles linked to tacrine moiety: in vitro and in vivo biological activities against Alzheimer's disease.

Alzheimer's disease (AD) is now ranked as the third leading cause of death after heart disease and cancer. There is no definite cure for AD due to the multi-factorial nature of the disease, hence, multi-target-directed ligands (MTDLs) have attracted lots of attention. In this work, focusing on the efficient cholinesterase inhibitory activity of tacrine, design and synthesis of novel arylisoxazole-tacrine analogues was developed. In vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition assay confirmed high potency of the title compounds. Among them, compounds 7l and 7b demonstrated high activity toward AChE and BChE with IC50 values of 0.050 and 0.039 µM, respectively. Both compounds showed very good self-induced Aß aggregation and AChE-induced inhibitory activity (79.4 and 71.4% for compound 7l and 61.8 and 58.6% for compound 7b, respectively). Also, 7l showed good anti-BACE1 activity with IC50 value of 1.65 µM. The metal chelation test indicated the ability of compounds 7l and 7b to chelate biometals (Zn2+, Cu2+, and Fe2+). However, they showed no significant neuroprotectivity against Aß-induced damage in PC12 cells. Evaluation of in vitro hepatotoxicity revealed comparable toxicity of compounds 7l and 7b with tacrine. In vivo studies by Morris water maze (MWM) task demonstrated that compound 7l significantly reversed scopolamine-induced memory deficit in rats. Finally, molecular docking studies of compounds 7l and 7b confirmed establishment of desired interactions with the AChE, BChE, and BACE1 active sites.

Evaluation of Anticancer and Epidermal Growth Factor Receptor Inhibition Activity by Benzochromeno Pyrimidin Derivatives in Three Human Cancer Cell Lines.

BACKGROUND: Cancer therapy is one of the most important challenges that human beings are facing. The abnormal activity of epidermal growth factor receptor tyrosine kinase (EGFR1) in tumors has been reported in many studies. Tyrosine kinase inhibitors are now commercially available for the treatment of a variety of cancers. Based on our previous studies, we assumed that a hybrid of aminopyrimidine derivatives as EGFR inhibitors and benzocheromen derivatives as cytotoxic agents can induce apoptosis in EGFR positive cancer cells. In the present study, the cytotoxic effect, ability of EGFR inhibition and apoptosis induction of some synthetic benzochromene pyrimidine derivatives were investigated on MDA-MB231, SKBR3 and PC3 cell lines. METHODS: The EGFR inhibition activity was determined using cell-based EGFR ELISA kit. Cell viability was determined by MTT assay in 2D and 3D cultures. The apoptosis was confirmed through different methods such as fluorescent staining, annexin V- propidium iodide double staining, DNALadder assay, caspase-3 colorimetric assay, and nitric oxide assay. RESULTS: The results of the MTT assay showed that derivatives with different substituents exhibited differential cytotoxicity in three cancer cell lines, although in MDA-MB231 the cytotoxicity effect of compounds is more obvious than the other cell lines. Production of nitric oxide, caspase-3 activity and DNA-fragmentation was significant in MDA-MB231 and PC3 cells. SKBR3 cells, despite having the lowest apoptosis among these three cell lines, showed a significant EGFR inhibition in the ELISA assay. CONCLUSION: In this research, we proved that hybrids of benzochromene and amino pyrimidine could be effective on growth inhibition of cancer cell lines and may be used as a drug candidate for cancer therapy in the future.

Phytochemical constituents and biological activities of Salvia macrosiphon Boiss.

Salvia macrosiphon Boiss. is an aromatic perennial herb belonging to the family Lamiaceae. Phytochemical studies and biological activities of this plant have been rarely documented in the literature. The current study aimed to investigate antibacterial and cytotoxic activity of different fractions of aerial parts of S. macrosiphon. Also, we tried to isolate and identify cytotoxic compounds from the plant. In this respect, the hydroalcoholic extract of the corresponding parts of the plant was fractionated into four fractions. Then, antibacterial and cytotoxic activity of each fraction were examined. It was found that the chloroform fraction had a good antibacterial activity against gram-positive and gram-negative bacteria. The most potent cytotoxicity was also obtained by the n-hexane fraction comparing with etoposide as the reference drug which was selected for the study and characterization of secondary metabolites. Accordingly, 13-epi manoyl oxide (1), 6α-hydroxy-13-epimanoyl oxide (2), 5-hydroxy-7,4'-dimethoxyflavone (3), and ß-sitosterol (4) were isolated and evaluated for their cytotoxic activity. Among them, compound 1 revealed significant cytotoxicity against A549, MCF-7, and MDA-MB-231. It merits mentioning that it showed high selectivity index ratio regarding the low cytotoxic effects on Human Dermal Fibroblast which can be considered as a promising anticancer candidate.

HPLC methods for quantifying anticancer drugs in human samples: A systematic review.

Pharmacokinetic (PK) study of anticancer drugs in cancer patients is highly crucial for dose selection and dosing intervals in clinical applications. Once an anticancer drug is administered, it undergoes various metabolic pathways; to determine these pathways, it is necessary to follow the administered drug in biological samples via different analytical methods. In addition, multi-drug quantification methods in patients undergoing multi-drug regimens of cancer therapy can have several benefits, such as reduced sampling time and analysis costs. In order to collect and categorize these studies, we conducted a systematic review of HPLC methods reported for the analysis of anticancer drugs in biological samples. A systematic search was performed on PubMed Medline, Scopus, and Web of Science databases, and 116 studies were included. In summary of included studies, when the objective of a method was to quantify a single drug, MS, or UV detectors were utilized equivalently. On the other hand, in methods with the aim of quantifying drug and metabolite(s) in a single run, MS detectors were the most utilized. This review can provide a comprehensive insight for researchers prior to developing a quantification method and selecting a detector.

Thieno[2,3-b]pyridine amines: Synthesis and evaluation of tacrine analogs against biological activities related to Alzheimer's disease.

In search of safer tacrine analogs, various thieno[2,3-b]pyridine amine derivatives were synthesized and evaluated for their inhibitory activity against cholinesterases (ChEs). Among the synthesized compounds, compounds 5e and 5d showed the highest activity towards acetylcholinesterase and butyrylcholinesterase, with IC50 values of 1.55 and 0.23 µM, respectively. The most active ChE inhibitors (5e and 5d) were also candidates for further complementary assays, such as kinetic and molecular docking studies as well as studies on inhibitory activity towards amyloid-beta (ßA) aggregation and ß-secretase 1, neuroprotectivity, and cytotoxicity against HepG2 cells. Our results indicated efficient anti-Alzheimer's activity of the synthesized compounds.

A review on progression of epidermal growth factor receptor (EGFR) inhibitors as an efficient approach in cancer targeted therapy.

The identification of molecular agents inhibiting specific functions in cancer cells progression is considered as one of the most successful plans in cancer treatment. The epidermal growth factor receptor (EGFR) over-activation is observed in a vast number of cancers, so, targeting EGFR and its downstream signaling cascades are regarded as a rational and valuable approach in cancer therapy. Several synthetic EGFR tyrosine kinase inhibitors (TKIs) have been evaluated in recent years, mostly exhibited clinical efficacy in relevant models and categorized into first, second, third and fourth-generation. However, studies are still ongoing to find more efficient EGFR inhibitors in light of the resistance to the current inhibitors. In this review, the importance of targeting EGFR signaling pathway in cancer therapy and related epigenetic mutations are highlighted. The recent advances on the discovery and development of different EGFR inhibitors and the use of various therapeutic strategies such as multi-targeting agents and combination therapies have also been reviewed.