homocamptothecin and Neoplasms

The delivery of therapeutic cancer agents using nanomaterials has recently attracted much attention. Although encouraging progress with chemotherapeutics has been made, tumor treatment response remains unsatisfactory. To address this concern, we constructed a new micellar nanocomplex by covalently conjugating hyaluronic acid (HA) with an iron oxide nanoparticle (IONP). When an external magnetic field was applied to the tumor area, HA-IONP specifically accumulated in the tumor, due to the strong IONP magnetism. In addition, HA was shown to bind to cluster determinant 44 (CD44), which is overexpressed on tumor cells. With combined magnetic, CD44, and enhanced permeability retention (EPR) targeting, the efficient delivery of HA-IONP to the tumor is expected to enhance cancer treatment efficiency. After encapsulation of the chemotherapy drug homocamptothecin (HCPT), the theranostic potency of HA-IONP/HCPT (HIH) was investigated both in vitro and in vivo. The improved tumor homing behavior of HIH was observed by magnetic resonance imaging (MRI) when an external magnetic field was used. Moreover, HIH showed remarkable tumor ablation efficiency, with magnetic targeting after 3 mg kg

Topics: Administration, Intravenous; Animals; Apoptosis; Camptothecin; Cell Line, Tumor; Drug Carriers; Female; Ferric Compounds; Humans; Hyaluronan Receptors; Hyaluronic Acid; Magnetic Fields; Magnetic Resonance Imaging; Mice; Mice, Nude; Micelles; Nanoparticles; Neoplasms; Positron-Emission Tomography; Theranostic Nanomedicine

We synthesized a pH-responsive conjugate of 10-hydroxycamptothecin-thiosemicarbazide-linear polyethylene glycol 2000 (PEG2000). The conjugate was confirmed by matrix-assisted laser desorption time of flight mass spectrometry,

Topics: Animals; Antineoplastic Agents, Phytogenic; Camptothecin; Carbon-13 Magnetic Resonance Spectroscopy; Cell Line, Tumor; Delayed-Action Preparations; Drug Carriers; Drug Delivery Systems; Drug Liberation; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Endocytosis; Humans; Hydrogen-Ion Concentration; Mice, Inbred BALB C; Micelles; Neoplasms; Prodrugs; Proton Magnetic Resonance Spectroscopy; Rats; Solubility; Spectrometry, Fluorescence; Tissue Distribution

Six 9-(heteroarylmethylidene)amino derivatives, 2a-2f, of homocamptothecin were synthesized for the first time by total synthesis in 22 steps and biologically evaluated as inhibitors of topoisomerase I. Moreover, the antitumor activities of 2a-2f against three human tumor cell lines, i.e., A-549, MDA-MB-435, and HCT-116, were determined and the results showed that compound 2c was the most active homocamptothecin derivative against the A-549 (IC(50) =0.046 μM) and HTC-116 tumor cells (IC(50) =3.67 μM), with a ca. 50 times higher activity than the reference drug topotecan (TPT) against the lung cancer cell line A-549.

Topics: Antineoplastic Agents; Camptothecin; Cell Line, Tumor; Cell Proliferation; DNA Topoisomerases, Type I; Drug Screening Assays, Antitumor; Humans; Neoplasms; Topoisomerase I Inhibitors

Homocamptothecin (hCPT) is a camptothecin (CPT) homologue with the insertion of a methylene (CH₂) spacer between the alcohol moiety and carbonyl group of the classical six-membered α-hydroxylactone ring. This modification provides higher lactone stability and did not impair its activity against topoisomerase I (Topo I), but rather appears to improve it compared to CPT. In an attempt to improve the antitumor activity of homocamptothecins, a series of novel hCPT derivatives conjugating with dihydropyrimidine (DHPM) derivatives was designed and synthesized based on a synthetic route which couples 7-formylhomocamptothecin with different dihydropyrimidine derivates. Most of the synthesized compounds exhibited good antiproliferative activity on tumor cell lines A549, MDA-MB-435 and HCT116. Furthermore, this class of compounds showed superior Topo I inhibition activity comparable to or higher than CPT.

Topics: Antineoplastic Agents; Camptothecin; Cell Line, Tumor; Cell Proliferation; DNA Topoisomerases, Type I; HCT116 Cells; Humans; Neoplasms; Pyrimidines; Topoisomerase I Inhibitors