20 research outputs found
Synthesis and antiproliferative activities of quebecol and its analogs
Simple and efficient synthesis of quebecol and a number of its analogs was accomplished in five steps. The synthesized compounds were evaluated for antiproliferative activities against human cervix adenocarcinoma (HeLa), human ovarian carcinoma (SK-OV-3), human colon carcinoma (HT-29), and human breast adenocarcinoma (MCF-7) cancer cell lines. Among all the compounds, 7c, 7d, 7f, and 8f exhibited antiproliferative activities against four tested cell lines with inhibition over 80% at 75 ÎĽM after 72 h, whereas, compound 7b and 7g were more selective towards MCF-7 cell line. The IC50 values for compounds 7c, 7d, and 7f were 85.1 ÎĽM, 78.7 ÎĽM, and 80.6 ÎĽM against MCF-7 cell line, respectively, showing slightly higher antiproliferative activtiy than the synthesized and isolated quebecol with an IC50 value of 104.2 ÎĽM against MCF-7.
[Refer to PDF for graphical abstract
A BODIPY-embedding miltefosine analog linked to cell-penetrating Tat(48-60) peptide favors intracellular delivery and visualization of the antiparasitic drug
Enhanced Cellular Uptake of Short Polyarginine Peptides through Fatty Acylation and Cyclization
Design, Synthesis, and Evaluation of Chitosan Conjugated GGRGDSK Peptides as a Cancer Cell-Targeting Molecular Transporter
Targeting cancer cells using integrin receptor is one of the promising targeting strategies in drug delivery. In this study, we conjugated an integrin-binding ligand (GGRGDSK) peptide to chitosan oligosaccharide (COS) using (sulfo-SMCC) bifunctional linker affording COS-SMCC-GGRGDSK. The conjugated polymer was characterized by FT-IR, 1H NMR, 13C NMR, and SEM. COS-SMCC-GGRGDSK did not show cytotoxicity up to a concentration of 1 mg/mL in the human leukemia cell line (CCRF-CEM). The conjugate was evaluated for its ability to enhance the cellular uptake of cell-impermeable cargoes (e.g., FAM and F′-G(pY)EEI phosphopeptide) in CCRF-CEM, and human ovarian carcinoma (SK-OV-3) cancer cell lines. Additionally, RGD modified and unmodified COS polymers were used to prepare nanoparticles by ionic gelation and showed particle size ranging from 187 to 338 mm, and zeta potential of 12.2–18.3 mV using dynamic light scattering. The efficiency of COS-NPs and COS-SMCC-RGDSK NPs was assayed for translocation of two synthetic cytotoxic agents ((2-(2-aminoethylamino)-4-(4-chlorophenyl)-6-(1H-indol-3-yl) nicotinonitrile (ACIN), and 2-(2-aminoethylamino)-6-(1H-indol-3-yl)-4-(4-methoxyphenyl)-nicotinonitrile (AMIN)) into CCRF-CEM and human prostate (DU-145) cancer cell lines. The results showed a dramatic reduction in the cell viability on their treatment with RGD targeted COS NPs in comparison to paclitaxel (PTX), free drug, and drug-loaded COS NPs
Cyclic Peptide–Selenium Nanoparticles as Drug Transporters
A cyclic peptide composed of five
tryptophan, four arginine, and
one cysteine [W<sub>5</sub>R<sub>4</sub>C] was synthesized. The peptide
was evaluated for generating cyclic peptide-capped selenium nanoparticles
(CP–SeNPs) in situ. A physical mixing of the cyclic peptide
with SeO<sub>3</sub><sup>–2</sup> solution in water generated
[W<sub>5</sub>R<sub>4</sub>C]–SeNPs via the combination of
reducing and capping properties of amino acids in the peptide structure.
Transmission electron microscopy (TEM) images showed that [W<sub>5</sub>R<sub>4</sub>C]–SeNPs were in the size range of 110–150
nm. Flow cytometry data revealed that a fluorescence-labeled phosphopeptide
(F′-PEpYLGLD, where F′ = fluorescein) and an anticancer
drug (F′-dasatinib) exhibited approximately 25- and 9-times
higher cellular uptake in the presence of [W<sub>5</sub>R<sub>4</sub>C]–SeNPs than those of F′-PEpYLGLD and dasatinib alone
in human leukemia (CCRF-CEM) cells after 2 h of incubation, respectively.
Confocal microscopy also exhibited higher cellular delivery of F′-PEpYLGLD
and F′-dasatinib in the presence of [W<sub>5</sub>R<sub>4</sub>C]–SeNPs compared to the parent fluorescence-labeled drug
alone in human ovarian adenocarcinoma (SK-OV-3) cells after 2 h of
incubation at 37 °C. The antiproliferative activities of several
anticancer drugs doxorubicin, gemcitabine, clofarabine, etoposide,
camptothecin, irinotecan, epirubicin, fludarabine, dasatinib, and
paclitaxel were improved in the presence of [W<sub>5</sub>R<sub>4</sub>C]–SeNPs (50 μM) by 38%, 49%, 36%, 36%, 31%, 30%, 30%,
28%, 24%, and 17%, respectively, after 48 h incubation in SK-OV-3
cells. The results indicate that CP–SeNPs can be potentially
used as nanosized delivery tools for negatively charged biomolecules
and anticancer drugs