Zinc-Mediated C-3 α-Prenylation of Isatins with Prenyl Bromide: Access to 3-Prenyl-3-hydroxy-2-oxindoles and Its Application.

A convenient and highly α-regioselective strategy for the synthesis of 3-prenyl-3-hydroxy-2-oxindoles has been developed starting from isatins and prenylzinc with good to excellent yields. This protocol provides a straightforward and practical way to introduce an α-prenyl moiety into the C-3 position of isatins. The advantages of this reaction are use of the cheap and readily available reagents, operational simplicity, and wide substrate scope. Furthermore, this transformation was applied to the synthesis of several oxindole-containing natural products, which further demonstrated the synthetic utility of this methodology.

One-pot synthesis of 1,4-dihydroxy-2-((E)-1-hydroxy-4-phenylbut-3-enyl)anthracene-9,10-diones as novel shikonin analogs and evaluation of their antiproliferative activities.

A series of shikonin analogs have been synthesized in a one-pot reaction of quinizarin with ß,γ-unsaturated aldehydes in MeOH under mild conditions and investigated for their cytotoxicity against four cancer cell lines and one normal cell line. The synthesized compounds were found to be cytotoxic against HeLa cells with no apparent toxicity against normal cell line. Further modification led to the discovery of a novel tetracyclic anthraquinone (4b/4b') with potent cytotoxic activities against cervical, breast and pancreatic cancer cell lines with no significant effect on the growth of the control mammary epithelial cell line MCF-10. The good cytotoxicity and selectivity of compound 4b/4b' suggest that it could be a promising lead for further optimization.

Synthesis of Furo[3,2-c]benzopyrans via an Intramolecular [4 + 2] Cycloaddition Reaction of o-Quinonemethides.

An intramolecular [4 + 2] cycloaddition reaction of o-quinonemethides generated from salicylaldehydes and α-prenylated alcohols is described. In the presence of a catalytic amount of benzenesulfonic acid (BSA), the reaction proceeded smoothly in EtOH to afford furo[3,2-c]benzopyrans through a three-bond forming process in moderate to excellent yields with high diastereoselectivity. This reaction provides a simple and straightforward protocol to efficiently construct furo[3,2-c]benzopyran skeletons. A possible mechanism involving hemiacetal formation/hetero-Diels-Alder reaction is proposed to rationalize the observed results.

Histone Deacetylase Inhibitors in Tumor Immunotherapy.

BACKGROUND: With an increasing understanding of the antitumor immune response, considerable progress has been made in the field of tumor immunotherapy in the last decade. Inhibition of histone deacetylases represents a new strategy in tumor therapy and histone deacetylase inhibitors have been recently developed and validated as potential antitumor drugs. In addition to the direct antitumor effects, histone deacetylase inhibitors have been found to have the ability to improve tumor recognition by immune cells that may contribute to their antitumor activity. These immunomodolutory effects are desirable, and their in-depth comprehension will facilitate the design of novel regimens with improved clinical efficacy. OBJECTIVE: Our goal here is to review recent developments in the application of histone deacetylase inhibitors as immune modulators in cancer treatment. METHODS: Systemic compilation of the relevant literature in this field. RESULTS & CONCLUSION: In this review, we summarize recent advances in the understanding of how histone deacetylase inhibitors alter immune process and discuss their effects on various cytokines. We also discuss the challenges to optimize the use of these inhibitors as immune modulators in cancer treatment. Information gained from this review will be valuable to this field and may be helpful for designing tumor immunotherapy trials involving histone deacetylase inhibitors.

Design, synthesis and evaluation of belinostat analogs as histone deacetylase inhibitors.

Aim: Histone deacetylase (HDAC) is an attractive target for antitumor therapy. Therefore, the development of novel HDAC inhibitors is warranted. Materials & methods: A series of HDAC inhibitors based on N-hydroxycinnamamide fragment was designed as the clinically used belinostat analog using amide as the connecting unit. All target compounds were evaluated for their in vitro HDAC inhibitory activities and some selected compounds were tested for their antiproliferative activities. Conclusion: Among them, compound 7e showed an IC50 value of 11.5 nM in inhibiting the HDAC in a pan-HDAC assay, being the most active compound of the series.

Green Method To Preparing Oxindole-Fused Spirotetrahydrofuran Scaffolds through Methanesulfonic Acid-Catalyzed Cyclization Reactions of 3-Allyl-3-hydroxy-2-oxindole in Water.

Water is an ideal solvent for chemical transformations in environmentally friendly and sustainable processes. An operationally simple, metal-free, and green approach to the synthesis of oxindole-fused spirotetrahydrofurans from 3-allyl-3-hydroxy-2-oxindoles in water is described. This method requires only cheap methanesulfonic acid as a catalyst and eliminates the need of complicated reagents. This atom- and step-economical transformation is highly efficient, which provides a new approach for the construction of oxindole-fused spirotetrahydrofuran molecules with potential pharmaceutical interest.