Synthesis and Antiproliferatory Activities Evaluation of Multi-Substituted Isatin Derivatives

Abstract

A series of multi-substituted isatin derivatives were synthesized using the powerful Sandmeyer reaction. The structures of these derivatives were confirmed by 1H-NMR, 13C-NMR, and HR-MS. Inhibition of proliferation activities of these derivatives against human leukemia cells (K562), human hepatocellular carcinoma cells (HepG2) and human colon carcinoma cells (HT-29) were evaluated in vitro using the MTT assay. Among the series, compound 4l exhibited strong antiproliferatory activities against K562, HepG2 and HT-29 cells with IC50 values of 1.75, 3.20, and 4.17 μM, respectively. The morphological, growth inhibitory and apoptosic effects of compound 4l in K562 cells, wound healing effect in HepG2 cells, and tube formating effect in matrix gel of HUVEC cells were evaluated consequently. All results indicated that compound 4l could be used as a potential antitumor agent in further investigations.

Therapeutically actionable signaling node to rescue AURKA driven loss of primary cilia in VHL-deficient cells

“…NVP-BEZ235, an orally available PI3K, mTORC1 and mTORC2 inhibitor, was primarily used as a tool compound in our studies to identify the underlying pathways that regulated cilia formation in VHL -deficient cells. The reasoning for using NVP-BEZ235 as a tool compound as opposed to pursuing it as a lead compound, stemmed from early termination of clinical trials in RCC due to poor tolerability and modest clinical activity 45 despite the promising preclinical studies in breast 46 , colon 47 , liver 48 and other cancer models using this compound. Nonetheless, the strong rationale of inhibiting both PI3K and mTOR signaling has led to the continued search for alternate compounds that can inhibit AKT and mTOR signaling (ideally inhibiting both mTORC1 and mTORC2 complexes).…”

Evaluation of the Antibacterial Activity of Isatin against Campylobacter jejuni and Campylobacter coli Strains

“…Isatin derivatives with more complex structures, such as the hydrazide-hydrazone class, showed an IC 50 value >100 µM in the HEK-293 cell line of normal human embryonic kidney cells [42]. Isatin-thiadiazoline hybrids assayed with WI-38 normal human lung cell line showed IC 50 in the range of 64.62 to >100 µM [43], and a series of multi-substituted isatin was tested with normal human renal epithelial cells (2937) and normal human umbilical vein endothelial cells (UVEC), obtaining IC 50 > 100 µM and 61.83 µM, respectively [44].…”

Recent trends in the chemistry of Sandmeyer reaction: a review

“…Ding et al . [ 34 ] presented a valuable approach to obtain biologically active isatin derivatives which play an important role in pharmaceutical industry due to their excellent antitumor properties against a variety of cell lines (K562, HepG2, HT-29, HL60, etc.). Focusing the synthesis of isatin derivatives, a quite simple and easy pathway is outlined in Scheme 7 involving the condensation of aniline 33 with hydroxylamine hydrochloride at 90 °C and chloral hydrate in 2 mol/L of HCl and water solution to afford oxime 34 .…”

“…Focusing the synthesis of isatin derivatives, a quite simple and easy pathway is outlined in Scheme 7 involving the condensation of aniline 33 with hydroxylamine hydrochloride at 90 °C and chloral hydrate in 2 mol/L of HCl and water solution to afford oxime 34. Cyclization of this oxime (34) in the presence of sulfuric acid with subsequent bromination reaction afforded required isatin 36 in 86% yield.…”