Design, synthesis, in vitro and in silico evaluations of new isatin-triazine- aniline hybrids as potent anti- Alzheimer multi-target directed lead compounds.

Multi target directed ligands (MTDLs) are one of the promising tools for treatment of complex disease like Alzheimer's disease (AD). In this study, using rational design, we synthesized new 15 hybrids of the s-triazine, isatin and aniline derivatives as anti- AD compounds. The design was as way as that new compounds could had anti cholinesterase (ChE), antioxidant and biometal chelation ability.

Comparison of three synthetic transferrin mimetic small peptides to promote the blood-brain barrier penetration of vincristine liposomes for improved glioma targeted therapy.

The existence of the blood-brain barrier (BBB) makes the clinical chemotherapy of glioma a formidable challenge, because it hinders the passage of different chemotherapeutics into the brain and reduces the overall therapeutic efficiency. Therefore, it is necessary to design a drug delivery system in way that would favor the transportation of anti-cancer agents across the BBB and increase their selective accumulation within the tumor cells without affecting the normal tissues. Transferrin receptor (TfR) that shows an elevated level of expression on the BBB and glioma cells emerges as a promising tool for brain targeted delivery and glioma therapy.

Cytotoxicity and Immunogenicity Evaluation of Synthetic Cell-penetrating Peptides for Methotrexate Delivery.

Methotrexate (MTX) is one of the most effective therapeutics to treat different types of solid tumors; however, it suffers low permeability limiting its bioavailability and cellular uptake. To tackle this, we aim to design and fabricate different types of cell-penetrating peptides (CPPs) to improve the intracellular uptake of MTX without causing any immunogenic response. CPPs were synthesized by the solid-phase peptide synthesis method.

Surface modification with cholesteryl acetyl carnitine, a novel cationic agent, elevates cancer cell uptake of the PEGylated liposomes.

The present study aimed to synthesize cholesteryl acetyl carnitine (CAC), and surface modify the PEGylated liposomes with the intention of enhanced cancer cell uptake. For this, CAC synthesis was performed in amine-free esterification conditions and then four liposomal formulations of unmodified, CAC/PEG, and CAC + PEG-modified were prepared by ethanol injection method. Cytotoxicity of the liposomes was investigated in A549 cells, followed by cellular uptake assessments of coumarin 6 (C6)-loaded liposomes.

Nanoparticles modified with vasculature-homing peptides for targeted cancer therapy and angiogenesis imaging.

The two major challenges in cancer treatment include lack of early detection and ineffective therapies with various side effects. Angiogenesis is the key process in the growth, survival, invasiveness, and metastasis of many of cancerous tumors. Imaging of the angiogenesis could lead to diagnosis of tumors in the early stage and evaluation of the therapeutic responses.

Effects of self-assembled cell-penetrating peptides and their nano-complexes on ABCB1 expression and activity.

Objectives: Doxorubicin (Dox) is one of the most well-known chemotherapeutics that are commonly applied for a wide range of cancer treatments. However, in most cases, efflux pumps like P-glycoprotein (P-gp), expel the taken drugs out of the cell and decrease the Dox bioavailability. Expression of P-gp is associated with elevated mRNA expression of the ATP-binding cassette B1 (ABCB1) gene.

Design, Synthesis and Biological Evaluation of Novel Piperazinone Derivatives as Cytotoxic Agents.

In this study, a series of piperazin-2-one derivatives were prepared through bioisosteric substitution of the imidazole ring of L-778,123 (imidazole-containing FTase inhibitor) and rearrangement of groups based on the tipifarnib structure. Final compounds were evaluated for their cytotoxic activities on cancer and normal cell lines by MTT assay. Methyl α-bromophenylacetic acid and 1-(3-chlorophenyl) piperazin-2-one were synthesized using previously described methods.

Synthesis and biological evaluation of diaryl urea derivatives designed as potential anticarcinoma agents using de novo structure-based lead optimization approach.

To develop inhibitors blocking VEGFR2 and the Raf/MEK/ERK mitogen-activated protein kinase signaling pathway new compounds based on sorafenib were designed, synthesized and biologically evaluated. Using de novo design method, a library of new ligands was generated and expanded. Considering in silico binding affinity towards VEGFR2, synthetic feasibility, and drug-likeness property, some of the designed ligands were selected for synthesis and screening for their in vitro antiproliferative activities against two cancer cell lines (HT-29 and A549).

The latest advances of cisplatin liposomal formulations: essentials for preparation and analysis.

: Cisplatin has been indicated for several malignancies all over the world for many years. Increasing patient tolerance for high dose of chemotherapeutics and reducing side effects has been granted by drug encapsulated liposomal systems. There have been much efforts for improving cisplatin delivery to the site of action via liposomes both in research and clinical trials such as SPI-077®, Liplacis®, and Lipoplatin®.

Self-assembled peptide nanoparticles for efficient delivery of methotrexate into cancer cells.

The low cellular uptake of Methotrexate (MTX), a commonly used anticancer drug, is a big challenge for efficient cancer therapy. Selfassembled peptide nanoparticles (SAPNs) are one of the major classes of peptide vectors that have gained much attention toward novel drug delivery systems. In the present study, different sequences of cell-penetrating peptides including R2W4R2 and W3R4W3 and their SAPNs (R2W4R2-E12 and W3R4W3-E12) were designed for efficient delivery of MTX into MCF7 breast cancer cells.

Drug Targeting Strategies Based on Charge Dependent Uptake of Nanoparticles into Cancer Cells.

The aim of this review was to describe the preferred charged nano-particles (CNPs) for targeted delivery in tumor cells. Zeta Potential (ZP), which represents the surface charge of NPs was highlighted in cell entrance and interactions. In this regard, various types of endocytosis pathways which are involved in NPs' uptake were first introduced.

Effects of N-terminal and C-terminal modification on cytotoxicity and cellular uptake of amphiphilic cell penetrating peptides.

Purpose: To assess the effect of "N-Acetylation and C-Amidation" on the cellular uptake, cytotoxicity and performance of amphiphilic cell penetrating peptides (CPP) loaded with methotrexate (MTX).

Methods: Several CPPs were synthesized by solid phase peptide synthesis method. Some of these sequences were modified with pyroglutamic acid at N-terminus and benzylamine or memantine at C-terminus.

Vancomycin Capped with Silver Nanoparticles as an Antibacterial Agent against Multi-Drug Resistance Bacteria.

Many antimicrobial medications are available to combat infections. However, the indiscriminate use of antibiotics has produced antibiotic resistance in the case of many bacterial pathogens. This study focuses on the development of nanoparticles (NPs) that enhance the in vitro antibiotic activity of vancomycin against multi-drug resistant (MDR) organisms.

Synthesis and cellular characterization of various nano-assemblies of cell penetrating peptide-epirubicin-polyglutamate conjugates for the enhancement of antitumor activity.

A new class of cell penetrating peptides (CPPs) named peptide amphiphile was designed to improve the intracellular uptake and the antitumor activity of epirubicin (EPR). Various amphiphilic CPPs were synthesized by solid phase peptide synthesis method and were chemically conjugated to EPR. Their corresponding nanoparticles (CPPs-E4 and CPPs-E8) were prepared via non-covalent binding of the peptides and polyanions.

Cellular uptake and anti-tumor activity of gemcitabine conjugated with new amphiphilic cell penetrating peptides.

Gemcitabine (Gem) is used as a single agent or in combination with other anticancer agents to treat many types of solid tumors. However, it has many limitations such as a short plasma half-life, dose-limiting toxicities and drug resistance. Cell-penetrating peptides (CPPs) are short peptides which may deliver a large variety of cargo molecules into the cancerous cells.

A comparison of liquid-based cytology with conventional Papanicolaou smears in cervical dysplasia diagnosis.

Background: Due to the high number of women affected by cervical cancer and the importance of an early diagnosis, combined with the frequent incidence of false-negative Papanicolaou (Pap) smear screening results for this disease, several studies have been conducted in recent years in order to find better tests. Liquid-based cytology (LBC) tests, including the liquid-based thin layer method, have demonstrated the highest potential for reducing false-negative cases and improved sample quality. This study aimed to compare the strength of the Pap smear test with fluid cytology and conventional tests in detecting cervical dysplasia.

Enhancing antitumor activity of silver nanoparticles by modification with cell-penetrating peptides.

Recently, silver nanoparticles (AgNPs) have been used for cancer treatment. To achieve a successful anticancer activity, AgNP needs to be delivered sufficiently to the cells. Cell-penetrating peptides (CPPs) are small cationic peptides that have ability to transport various cargos across cell membranes.

Nano-based strategies to overcome p-glycoprotein-mediated drug resistance.

Introduction: The discussion about cancer treatment has a long history. Chemotherapy, one of the promising approaches in cancer therapy, is limited in the clinic as plenty of factors evolve and prevent appropriate therapeutic response to drugs. Multi-drug resistance (MDR), which is mostly P-glycoprotein-mediated, is described as the most well-known impediment in this contribution.

Effect of poly-glutamate on uptake efficiency and cytotoxicity of cell penetrating peptides.

Cell penetrating peptides (CPPs) were developed as vehicles for efficient delivery of various molecules. An ideal CPP-peptide should not display any toxicity against cancer cells as well as healthy cells and efficiently enter into the cell. Because of the cationic nature and the intrinsic vector capabilities, these peptides can cause cytotoxicity.

The Relation Between Thermodynamic and Structural Properties and Cellular Uptake of Peptides Containing Tryptophan and Arginine.

Purpose: Cell-penetrating peptides (CPPs) are used for delivering drugs and other macromolecular cargo into living cells. In this paper, we investigated the relationship between the structural/physicochemical properties of four new synthetic peptides containing arginine-tryptophan in terms of their cell membrane penetration efficiency.

Methods: The peptides were prepared using solid phase synthesis procedure using FMOC protected amino acids.

Enhanced cellular internalization of CdTe quantum dots mediated by arginine- and tryptophan-rich cell-penetrating peptides as efficient carriers.

Quantum dots (QDs), as a new class of fluorescent tags, have been widely used for biomedical applications. Despite their various advantages, QDs do not efficiently enter cells on their own, and aggregation often occurs following internalization. In the present study, we have designed three QD-cell-penetrating peptide (CPP) complexes to increase the uptake of QD into cells.

Synthesis and in vitro evaluation of amphiphilic peptides and their nanostructured conjugates.

Purpose: Breast cancer is the second leading cancer type among people of advanced countries. Various methods have been used for cancer treatment such as chemotherapy and radiotherapy. In the present study we have designed and synthesized a new group of drug delivery systems (DDS) containing a new class of Cell Penetrating Peptides (CPPs) named Peptide Amphiphiles (PAs).

In-silico Investigation of Tubulin Binding Modes of a Series of Novel Antiproliferative Spiroisoxazoline Compounds Using Docking Studies.

Interference with microtubule polymerization results in cell cycle arrest leading to cell death. Colchicine is a well-known microtubule polymerization inhibitor which does so by binding to a specific site on tubulin. A set of 3', 4'-bis (substituted phenyl)-4'H-spiro [indene-2, 5'-isoxazol]-1(3H)-one derivatives with known antiproliferative activities were evaluated for their tubulin binding modes.

Comparison of Cytotoxic Activity of L778123 as a Farnesyltranferase Inhibitor and Doxorubicin against A549 and HT-29 Cell Lines.

Purpose: Farnesyltransferase (FTase) is a zinc-dependent enzyme that adds a farnesyl group to the Ras proteins. L778, 123 is a potent peptidomimetic imidazole-containing FTase inhibitor.

Methods: L778123 was synthesized according to known methods and evaluated alone and in combination with doxorubicin against A549 (adenocarcinomic human alveolar basal epithelial cells) and HT29 (human colonic adenocarcinoma) cell lines by MTT assay.

Tamoxifen loaded folic acid armed PEGylated magnetic nanoparticles for targeted imaging and therapy of cancer.

Magnetic nanoparticles (MNPs) have been widely used as drug delivery nanosystems and contrast agent for imaging and detection. To engineer multifunctional nanomedicines for simultaneous imaging and therapy of cancer cells, in the current study, we synthesized tamoxifen (TMX) loaded folic acid (FA) armed MNPs to target the folate receptor (FR) positive cancer cells. To this end, Fe3O4 nanoparticles (NPs) were synthesized through thermal decomposition of Fe(acac)3.