Design, Synthesis, and Antiproliferative Activity of Benzopyran-4-One-Isoxazole Hybrid Compounds.

The biological significance of benzopyran-4-ones as cytotoxic agents against multi-drug resistant cancer cell lines and isoxazoles as anti-inflammatory agents in cellular assays prompted us to design and synthesize their hybrid compounds and explore their antiproliferative activity against a panel of six cancer cell lines and two normal cell lines. Compounds - displayed significant antiproliferative activities against all the cancer cell lines tested, and IC values were in the range of 5.2-22.

Targeted Delivery of Cabazitaxel Using Cyclic Cell-Penetrating Peptide and Biomarkers of Extracellular Matrix for Prostate and Breast Cancer Therapy.

Targeted drug delivery for cancer therapy is an emerging area of research. Cancer cells overexpress certain biomarkers that can be exploited for their targeted therapy. Cyclic cell-penetrating peptides (cCPP) are increasingly assessed for intracellular cargo delivery in cancer cells.

Applications of amphipathic and cationic cyclic cell-penetrating peptides: Significant therapeutic delivery tool.

A new class of peptides, cyclic cell-penetrating peptides (CPPs), has great potential for delivering a vast variety of therapeutics intracellularly for treating diverse ailments. CPPs have been used previously; however, their further use is limited due to instability, toxicity, endosomal degradation, and insufficient cellular penetration. Cyclic CPPs are being investigated in delivering therapeutics to treat various ailments, including multi-drug resistant microbial infections, HIV, and cancer.

Cyclic Peptide-Gadolinium Nanoparticles for Enhanced Intracellular Delivery.

A cyclic peptide containing one cysteine and five alternating tryptophan and arginine amino acids [(WR)C] was synthesized using Fmoc/tBu solid-phase methodology. The ability of the synthesized cyclic peptide to produce gadolinium nanoparticles through an in situ one-pot mixing of an aqueous solution of GdCl with [(WR)C] peptide solution was evaluated. Transmission electron microscopy showed the formed peptide-Gd nanoparticles in star-shape morphology with a size of ~250 nm.

Cyclic Cell-Penetrating Peptides as Efficient Intracellular Drug Delivery Tools.

Cyclic cell-penetrating peptides are relatively a newer class of peptides that have a huge potential for the intracellular delivery of therapeutic agents aimed at treating challenging ailments like multidrug-resistant bacterial diseases, cancer, and HIV infection. Cell-penetrating peptides (CPPs) have been extensively explored as intracellular delivery vehicles; however, they have some inherent limitations like poor stability, endosomal entrapment, toxicity, and suboptimal cell penetration. Owing to their favorable properties that avoid these limitations, cyclic CPPs can provide a good alternative to linear CPPs.

EDB-FN Targeted Peptide-Drug Conjugates for Use against Prostate Cancer.

Prostate cancer (PCa) is the most common malignancy in men and is the leading cause of cancer-related male mortality. A disulfide cyclic peptide ligand [CTVRTSADC] has been previously found to target extra domain B of fibronectin (EDB-FN) in the extracellular matrix that can differentiate aggressive PCa from benign prostatic hyperplasia. We synthesized and optimized the stability of ligand by amide cyclization to obtain [KTVRTSADE] using Fmoc/tBu solid-phase chemistry.

Synthesis and Antiproliferative Activities of Conjugates of Paclitaxel and Camptothecin with a Cyclic Cell-Penetrating Peptide.

Cell-penetrating peptide [WR]₅ has been previously shown to be an efficient molecular transporter for various hydrophilic and hydrophobic molecules. The peptide was synthesized using Fmoc/tBu solid-phase chemistry, and one arginine was replaced with one lysine to enable the conjugation with the anticancer drugs. Paclitaxel (PTX) was functionalized with an esterification reaction at the C2' hydroxyl group of PTX with glutaric anhydride and conjugated with the cyclic peptide [W(WR)₄K(Ala)] in DMF to obtain the peptide-drug conjugate PTX1.

Antibiotics-Peptide Conjugates Against Multidrug-resistant Bacterial Pathogens.

The menace of multi-drug resistance by bacterial pathogens that are responsible for infectious diseases in humans and animals cannot be over-emphasized. Many bacteria develop resistance to antibiotics by one or more combination of resistance mechanisms namely, efflux pump activation thereby reducing bacteria intracellular antibiotic concentration, synthesizing a protein that protects target site causing poor antibiotic affinity to the binding site, or mutations in DNA and topoisomerase gene coding that alters residues in the binding sites. The ability to use a combination of these resistance mechanisms among others creates a phenomenon known as antimicrobial drug resistance.

Design, Synthesis, and Evaluation of Homochiral Peptides Containing Arginine and Histidine as Molecular Transporters.

Linear (HR) and cyclic [HR] peptides (n = 4,5) containing alternate arginine and histidine residues were synthesized. The peptides showed 0⁻15% cytotoxicity at 5⁻100 µM in human ovarian adenocarcinoma (SK-OV-3) cells while they exhibited 0⁻12% toxicity in human leukemia cancer cell line (CCRF-CEM). Among all peptides, cyclic [HR]₄ peptide was able to improve the delivery of a cell impermeable fluorescence-labeled phosphopeptide by two-fold.