Synthesis, characterization, molecular docking studies and biological evaluation of some novel hybrids based on quinazolinone, benzofuran and imidazolium moieties as potential cytotoxic and antimicrobial agents

Objective(s): Hybridization of bioactive natural and synthetic compounds is one of the most promising novel approaches for the design of hit and lead compounds with new molecular structures. In this investigation, a series of novel hybrid structures bearing quinazolinone, benzofuran and imidazolium moieties were designed and synthesized. Materials and Methods:Novel hybrid compounds were prepared and their structures were characterized by spectral and analytical data. In order to evaluate the biological activities, the synthesized hybrid compounds were studied for in vitro antibacterial activity against three Gram positive bacteria (Staphylococcus aureu, Bacillus subtilis, Listeria monocitogenes) and three Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Salmonella entritidis) and also, Candida albicans as one yeast-like fungi strain. Cytotoxic activities of the synthesized compounds were also evaluated by the MTT assay in the human breast cancer cell line (MCF-7) and finally docking studies of cytotoxic derivatives were performed on aromatase enzyme. Results:The results of antimicrobial activity showed that compound 14e, with two halogen atoms on quinazolinone and benzofuran was the most active against all the tested strains of microorganisms with the MIC value 16-128 µg/ml. Some of the tested compounds showed good cytotoxicity on MCF-7, and compound 14c with IC50=0.59 micromolar (μM) was found to be the most cytotoxic compound among the studied hybrid derivatives. The docking analysis showed acceptable binding interactions for these compounds. Conclusion: Based on the obtained results, the hybrid derivatives of quinazolinone, benzofuran and imidazolium could be regarded as efficient candidates for further molecular developments of anticancer and antimicrobial agents

Benzofuran as a promising scaffold for the synthesis of antimicrobial and antibreast cancer agents: A review

Benzofuran as an important heterocyclic compound is extensively found in natural products as well as synthetic materials. Since benzofuran drivatives display a diverse array of pharmacological activities, an interest in developing new biologically active agents from benzofuran is still under consideration. This review highlights recent findings on biological activities of benzofuran derivatives as antimicrobial and antibreast cancer agents and lays emphasis on the importance of benzofurans as a major source for drug design and development

Expression of apoptosis-Related genes bcl-2 and bax in rat brain hippocampus, followed by intraperitoneal injection of nanosilver

Background: Silver nanoparticles are small scale substance (<100 nm) used in food technology and medical industry. The data suggest that nanosilver may produce neurotoxicity by generating free radical-induced oxidative stress and by altering gene expression producing apoptosis and neurotoxicity. In this study, the apoptotic effects of Nano silver on apoptosis- related genes expression bcl-2 and bax on rat hippocampus, which is involved in memory and learning, was investigated. Materials & Methods: 28 male Wistar rats were divided into four groups of control and three groups of the treatment. The control group received saline and the treatment groups received intraperitoneal injections of silver nanoparticles at doses of 100, 200 and 400ppm. Ten days after the last injection, the hippocampal region was dissected and removed and then the expression of bcl-2 and bax genes was evaluated using semi-qualitative RT-PCR and Densitometry assay. Results: The expression of anti- apoptotic b-cl2 gene was reduced in the treatment groups compared to the control group. In comparison, the expression of pro- apoptotic bax gene was increased in the treatment groups compared to the control group. This apoptotic affects was increased at higher doses. Conclusion: The data suggest that silver nanoparticles may produce apoptosis by altering apoptosis- related genes expression, in rat brain hippocampus cells

The effect of COQ10 on mRNA expression of Mfn1 and Mfn2 genes in the liver of lead-infected rats

Background and Objective: Lead poisoning has harmful effects on various body organs. Coenzyme Q10 (COQ10) plays a decisive role in many biological activities, such as intracellular antioxidant protection. Apoptosis is expressed and regulated in the liver by the mfn1 and mfm2 family genes. We aimed to investigate the effect of COQ10 gastric gavage on the expression of these genes in the liver of lead-infected rats. Materials and Methods: Twenty-four male rats weighing 160-210 grams were randomly divided into three groups. The control group received deionized water. The intervention groups received either 1 mg/L lead dissolved in acetic acid or q mg/K pbcl12 lead table salt dissolved in acetic acid plus 10 mg/kg COQ10 for 28 days. The expression of mfn1 and mfn2 genes were investigated by the real-time polymerase chain reaction (PCR) method. Results: The expression of mfn1 mRNA at a dose of 1 mg/L in the group receiving lead significantly decreased compared with the control group (P&lt;0.05). In the group receiving lead+COQ10, a significant increase was seen in mfn1 expression compared with the lead group (P&lt;0.05). The mRNA expression of the mfn2 gene at a dose of 1 mg/L lead significantly decreased in the group receiving lead compared with the control group (P&lt;0.05). The mRNA expression of the mfn2 gene significantly increased at a dose of 1 mg/L lead and 10 mg/kg COQ10 in the group receiving lead+COQ10 compared with the lead group (P&lt;0.05). Conclusions: Lead induces apoptosis by reducing the expression of antiapoptotic genes mfn1 and mfn2, while COQ10 increases their expression

Delivery of letrozole-encapsulated niosomes via a 3D bioprinting gelatin–alginate scaffold for potential breast cancer treatment

Abstract 3D printing technology is a powerful tool in scaffold engineering for biomedical applications, especially in anticancer activities and drug delivery. The present study developed a 3D-printed gelatin–alginate scaffold incorporating letrozole-loaded niosomes (Let/Nio@Gel-AL-SC) as a more effective drug delivery system. The findings showed that the fabricated niosomes appeared spherical. 3D-printed scaffolds exhibited biodegradability and sustained drug-release properties. The drug release from the scaffold was less prominent under acidic conditions than physiological ones. Cytotoxicity analysis showed that the engineered Let/Nio@Gel-AL-SC scaffold exhibited significant cytotoxicity against MCF-7 cancer cells. Gene expression analysis demonstrated a significant decrease in the expression of BCL2, CCND1, MMP2, and CDK4 genes and a notable increase in the expression of BAX and P53 genes, as well as the activity of Caspase 3/7 enzyme following treatment with Let/Nio@Gel-AL-SC. In addition, flow cytometry analysis revealed that Let/Nio@Gel-AL-SC significantly reduced necrosis and dramatically increased apoptosis. Also, the Let/Nio@Gel-AL-SC formulation exhibited a significantly greater increase in ROS values. The incorporation of letrozole-loaded niosomes into 3D printing gelatin/alginate scaffold has enhanced the efficacy of anticancer therapy. This is demonstrated by the sustained release of drugs, which indicates a promising potential for effective anticancer activity. Consequently, this combination holds promise as a potential future cancer therapy strategy. Graphical abstrac

Folic acid-functionalized PEGylated niosomes co-encapsulated cisplatin and doxoribicin exhibit enhanced anticancer efficacy

Abstract The medical field is faced with the difficult task of developing a new approach to curing cancer, which is prevalent in organs such as the breast and ovaries and has a high mortality rate. Since chemotherapy is the conventional method of treatment, efforts are being made to improve it to help patients function better. Fortunately, with the use of nanocarriers and their remarkable ability to manage and direct drug delivery, progress is being made in cancer treatment. In addition, folic acid-coated nanocarriers offer several advantages in drug delivery, including improved stability, bioavailability, targeted delivery and drug solubility. These properties make them promising tools for improving cancer treatment efficacy. This research focused on investigating the stability of a specific niosomal formulation (consisting of Span 60 and cholesterol) under different temperature conditions (4 and 25 ℃) for 2 months. In addition, the drug release rate of the formulation was evaluated. The results showed that the size and polydispersity index increased significantly in the stability studies, but the entrapment efficiency% decreased dramatically over time. In addition, encapsulation of drugs in niosomal formulations resulted in stable and slow drug release. The cytotoxicity evaluation results of formulations containing doxorubicin and cisplatin show their significant inhibitory effect on both breast and ovarian cancer cell lines (IC50 for DOX–CIS–Nio@PEG–FA formulation was 6.11 and 17.87 µg/mL for A2780 and MCF-7, respectively). Niosomes loaded with a combination of two drugs were found to affect gene expression in the cancer cell lines tested. They decreased the expression of BCl2, VEGF, CCND1, and HER2 genes while increasing the expression of BAX gene. Flow cytometry results indicated that niosomes loaded with doxorubicin and cisplatin increased the rate of apoptosis in both cell lines compared to a drug mixture. ROS and cell cycle arrest, confirm the significant inhibition of cancer cells and their destruction in the presence of the synthesized noisome formulation in comparison to free drugs and the combination of two drugs. The potential of this novel approach for delivering drugs to cancer cells lies in the ability to combine treatments and target multiple cancers simultaneously. Such formulations allow co-delivery of drugs to different cancer cells, thereby improving the efficacy of chemotherapy through synergistic effects between drugs. Graphical Abstrac