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Bioorganic & Medicinal Chemistry Letters Feb 2017Cyclic imides are well known to be very important antitumor agents such as mitonafide and amonafide etc. Based on this fact, we have synthesized two series of cyclic...
Cyclic imides are well known to be very important antitumor agents such as mitonafide and amonafide etc. Based on this fact, we have synthesized two series of cyclic imide derivatives containing two cyclic imide moiety in their structures (bis-cyclic imides) and screened them for in vitro anticancer activity against five human cancer cell lines i.e. breast (T47D), lung (NCl H-522), colon (HCT-15), ovary (PA-1) and liver (Hep G2). One series of bis-cyclic imide derivatives (3a-h) have been synthesized by condensation of acid anhydrides (1a-b) with diamines (2a-d) and another series (9a-f, 10a-f, 11a-f and 12a-f) by condensation of various diamines (4a-f) with diacids (5-8) in good yields. Structures assigned to 3a-h, 9a-f, 10a-f, 11a-f and 12a-f were fully characterized by spectroscopic means and elemental analysis. On screening for in vitro anticancer activity, compounds 3a (breast T47D), 3d (breast T47D, liver Hep G2), 3e (breast T47D, liver Hep G2), 3h (colon HCT-15), 10f (liver Hep G2) and 11a (colon HCT-15, ovary PA-1) exhibited good anticancer activities with IC values range from 12.41±3.2 to 17.9±2.5μM.
Topics: Antineoplastic Agents; Cell Proliferation; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Imides; Microwaves; Molecular Structure; Structure-Activity Relationship
PubMed: 28011220
DOI: 10.1016/j.bmcl.2016.12.031 -
European Journal of Medicinal Chemistry Oct 2014A novel series of metal complexes of naphthalimide-cyclam conjugates were synthesized and their in vitro antitumor activities were evaluated. The newly-synthesized...
A novel series of metal complexes of naphthalimide-cyclam conjugates were synthesized and their in vitro antitumor activities were evaluated. The newly-synthesized compounds showed huge diversity of antiproliferative potency due to variety of metal ions and length of alkyl chains, among which the Zn(II) and Cr(III) complexes exhibited comparable antiproliferative activities with amonafide via multiple tyrosine kinase inhibition. Further research revealed that the representative compound 8a displayed broad-spectrum antiproliferative activity against 15 cancer cell lines with average IC50 value 10.18 ± 3.25 μM, and effective antiangiogenic activity on human microvascular endothelial cells (HMEC-1). In brief, metal complexes of naphthalimide-cyclam conjugates were firstly designed and synthesized as multi-target tyrosine kinase inhibitors and proved of their antitumor capacities.
Topics: Antineoplastic Agents; Cell Line, Tumor; Cell Movement; Cell Proliferation; Chemistry Techniques, Synthetic; Down-Regulation; Drug Screening Assays, Antitumor; Heterocyclic Compounds; Humans; Naphthalimides; Organometallic Compounds; Protein Kinase Inhibitors; Receptor Protein-Tyrosine Kinases; Signal Transduction; Structure-Activity Relationship
PubMed: 25084146
DOI: 10.1016/j.ejmech.2014.07.068 -
Journal of Materials Chemistry. B Nov 2014Quantum dots (QDs) have shown great potential in monitoring and imaging cancer cells because of their unique photochemical and photophysical properties. However, it is...
Quantum dots (QDs) have shown great potential in monitoring and imaging cancer cells because of their unique photochemical and photophysical properties. However, it is little-known whether QDs affect the cellular internalization, proliferation and apoptosis. Here a new class of multifunctional QDs capped with ligands that possess l-Lys or l-Arg and naphthalimide (NI), linked by carboxyl groups (l-Lys-NI@QDs and l-Arg-NI@QDs, respectively), have been synthesized. We found that these QDs are of controllable sizes, in the range of 4 to 5 nm and have strong optical emission properties. The cellular uptake of NI derivative-capped QDs was monitored by flow cytometry and confocal microscopy. The results of in vitro cytotoxicity revealed that NI derivative-capped QDs, with better cell selectivity, could inhibit the growth of multiple cancer cells more potently than amonafide. They effectively inhibited the proliferation of cells due to apoptosis, which was confirmed by Hoechst 33342, annexin V-FITC and JC-1 staining and mitochondrial membrane potential (MMP) experiments. The most potent NI derivative-capped QDs, l-Arg-NI@CdSe/ZnS, were verified to efficiently induce apoptosis via a reactive oxygen species (ROS) mediating mitochondrial dysfunction, and were more effective in promoting programmed cell death in HepG2 cells in a preliminary mechanistic study.
PubMed: 32261959
DOI: 10.1039/c4tb01048e