Design and synthesis of new trimethoxylphenyl-linked combretastatin analogues loaded on diamond nanoparticles as a panel for ameliorated solubility and antiproliferative activity

Abstract

A new series of vinyl amide-, imidazolone-, and triazinone-linked combretastatin A-4 analogues have been designed and synthesised. These compounds have been evaluated for their cytotoxic activity against MDA-MB-231 breast cancer cells. The triazinone-linked combretastatin analogues (6 and 12) exhibited the most potent cytotoxic activity, in sub-micromolar concentration compared with combretastatin A-4 as a reference standard. The results of β-tubulin polymerisation inhibition assay appear to correlate well with the ability to inhibit β-tubulin polymerisation. Additionally, these compounds were subjected to biological assays relating to cell cycle aspects and apoptosis induction. In addition, the most potent compound 6 was loaded on PEG-PCL modified diamond nanoparticles (PEG-PCL-NDs) and F4 was picked as the optimum formula. F4 exhibited enhanced solubility and release over the drug suspension. In the comparative cytotoxic activity, PEG-PCL modified F4 was capable of diminishing the IC50 by around 2.89 times for nude F4, while by 3.48 times relative to non-formulated compound 6 .

Design, Synthesis, Docking Study, and Antiproliferative Evaluation of Novel Schiff Base–Benzimidazole Hybrids with VEGFR-2 Inhibitory Activity

“…Accordingly, compounds 3e and 3g were selected to be further investigated for their impact on induction of apoptosis in the NCI-H460 lung cancer cell line. The NCI-H460 cells were treated with compounds 3e and 3g for 24 h at a concentration equal to their IC 50 value and then analyzed for the apoptosis percentage via FACS detection using Annexin V-FITC and PI dual staining [ 25 ]. As illustrated in Figure 4 , the tested cancer cells displayed an increase in the percentage of apoptotic cells following exposure treatment with compounds 3e and 3g as observed with untreated control cells.…”

“…Finally, and in continuation of our previous research and efforts to synthesize novel heterocyclic compounds bearing various bioactive scaffolds of efficient anticancer activity [ 25 , 26 ], the present work depends on the hybridization of the well-known biologically active entities Schiff base and benzimidazole scaffolds. Our synthesized compounds were tested as anti-cancer candidates targeting VEGFR-2 inhibitors with the analysis of their apoptotic anti-proliferative activities, in the hope that this synergistic hybridization may lead to a more selective, safe, and efficient drug.…”

Design, synthesis and antiproliferative screening of newly synthesized coumarin-acrylamide hybrids as potential cytotoxic and apoptosis inducing agents

“…These interactions may potentially explain the remarkable tubulin inhibitory activity observed for coumarin-acrylamide compound 6e. [33][34][35]…”

Synthesis, Characterization and Biological Evaluation of New Enamide Fluorinated‐Schiff Base Derivatives as Potential Cytotoxic and Apoptosis‐Inducing Agents

“…Most of the chemotherapeutic compounds exert cytotoxic effect by altering cell cycle at specific checkpoint and induction of cellular apoptotic death. [32,33] The inappropriate regulation of cellular cycle by anticancer agents has been considered to be an effective strategy in the development of new anticancer regimens. [34] Therefore, it is of interest to examine the effect of compound 5 on cell cycle stage progression in MCF-7 cancer cells by using FACS method.…”