Histone dacetylases (HDACs) are a group of enzymes that remove acetyl groups from histones and regulate expression of tumor suppressor genes. They are implicated in many human diseases, especially cancer, making them a promising therapeutic target for treatment of the latter by developing a wide variety of inhibitors. HDAC inhibitors interfere with HDAC activity and regulate biological events, such as cell cycle, differentiation and apoptosis in cancer cells. As a result, HDAC inhibitor-based therapies have gained much attention for cancer treatment. To date, the FDA has approved three HDAC inhibitors for cutaneous/peripheral T-cell lymphoma and many more HDAC inhibitors are in different stages of clinical development for the treatment of hematological malignancies as well as solid tumors. In the intensifying efforts to discover new, hopefully more therapeutically efficacious HDAC inhibitors, molecular modeling-based rational drug design has played an important role in identifying potential inhibitors that vary in molecular structures and properties. In this review, we summarize four major structural classes of HDAC inhibitors that are in clinical trials and different computer modeling tools available for their structural modifications as a guide to discover additional HDAC inhibitors with greater therapeutic utility.

https://www.mdpi.com/1420-3049/20/3/3898/pdf

Histone deacetylase inhibitors in clinical studies as templates for new anticancer agents.

Piperlongumine, a potent anticancer phytotherapeutic: Perspectives on contemporary status and future possibilities as an anticancer agent

Copper-Catalyzed Asymmetric Borylallylation of Vinyl Arenes.

Piperaceae plants consist of about 3600 species, of which about 2000 are Piper plants. Their habitat is distributed across pantropical regions. The representative plant is Piper nigrum, known as black pepper. These plants have been widely used in folk medicine in Korean traditional medicine. This review collected papers identifying and separating the amides obtained from these Piper plants, with a focus on Piper amides potential to control the production and growth of fungal strains that cause plant disease and their insecticidal properties against agricultural pests. Piper amide benefits include antiaflatoxigenic activities, antiparasitic activities, anticancer properties, antiplatelet activities, and anti-inflammatory activities, among other therapeutic properties for the treatment of human diseases. In addition, this review paper provides a total synthesis study on the mass production of Piper amides and their derivatives, with a formulation study for industrial use. This review paper is designed to help inform future studies on Piper amide applications.

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Naturally occurring Piper plant amides potential in agricultural and pharmaceutical industries: perspectives of piperine and piperlongumine

Synthesis and biological evaluation of new homocamptothecin analogs.

Synthesis of the key intermediate of ramelteon

Synthesis and biological evaluation of piperamide analogues as HDAC inhibitors

A concise formal synthesis of camptothecin is described. The key pyrido-lactone (DE ring) was prepared effectively starting from 2-chloronicotinic acid via lithiation, reduction, and hydrolysis in 29% overall yield.

Synthesis of the DE synthon of racemic camptothecin

The invention discloses a method for synthesizing key intermediate (S)-4-ethyl-4-hydroxyl-1,7-dihydro-tetrahydro-pyran[3,4-c]pyridine-3,8-one for preparing camptothecine compounds, which is characterized in that the intermediate is synthesized by using a nicotinic acid derivative as raw material and (2R)-1,2-O-isopropylidenedioxy-3-pentanone as a chiral inducing reagent and by the following steps: carrying out the nucleophilic reaction of an intermediate generated by the treating the nicotinic acid derivative with a lithium reagent and the chiral inducing reagent, and treating a resulting lactone compound with diluted hydrochloric acid; reducing the lactone into a glycol compound; protecting the glycol compound; removing N,N'-isopropylidene protecting groups; oxidizing an o-glycol compound into a formyl; oxidizing the formyl into an acid; removing an alcohol protecting group; hydrolyzing an ether to form a hydroxyl; and obtaining the target substance by tautomerism. The method has theadvantages of high yield and high stereoselectivity.

Method for synthesizing key intermediate for preparing camptothecine compounds

The invention discloses a preparation method of a medicine midbody 2-amino-5-alkoxy propiophenone. The method takes m-chlorophenyl propanone as a starting material and comprises the following steps of: (a) carrying out nitration reaction on the m-chlorophenyl propanone to obtain a 2-nitryl-5-chlorophenyl propanone compound; (b) carrying out ketal reaction on the 2-nitryl-5-chlorophenyl propanone; (c) carrying out etherification reaction in which Cl atom is substituted by a nucleophilic reagent; (d) hydrolyzing ketal; and (e) reducing nitryl. The invention has the advantages of high yield and easy purification, and can realize large-scale industrialized production better.

Haomin Liu

Papers

Synthesis of the key intermediate of ramelteon

Synthesis and biological evaluation of piperamide analogues as HDAC inhibitors

Synthesis of the DE synthon of racemic camptothecin

Method for synthesizing key intermediate for preparing camptothecine compounds

Preparation method of 2-amino-5-alkoxy propiophenone