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Synthesis and Evaluation of Bioactivity of Enzyme Inhibitors

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A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: 29 August 2024 | Viewed by 5377

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Special Issue Editors

Prof. Dr. Fen Er Chen

E-Mail Website
Guest Editor

Department of Chemistry, Fudan University, Shanghai, China
Interests: drug design; anti-HIV; NNRTI; continuous flow chemistry; green synthesis and catalysis

Dr. Shuai Wang

E-Mail Website
Guest Editor Assistant

Department of Chemistry, Fudan University, Shanghai, China
Interests: drug design; anticancer; anti-HIV; NNRTI; combinatorial chemistry strategies

Special Issue Information

Dear Colleagues,

Enzyme inhibitors have been widely studied in the field of drug discovery and development due to their potential therapeutic applications. Inhibiting enzymes that are involved in disease pathways can lead to the development of new drugs for the treatment of various diseases. The synthesis and evaluation of bioactivity of enzyme inhibitors is an important area of research that involves the design, synthesis, and testing of compounds that can selectively inhibit specific enzymes. This Special Issue aims to highlight recent advances in the synthesis and evaluation of bioactivity of enzyme inhibitors. As the guest editor, I am excited to present a collection of articles that cover a range of topics related to enzyme inhibitors, including the design and synthesis of novel inhibitors, the evaluation of their bioactivity, and their potential therapeutic applications. Overall, this Special Issue provides a comprehensive overview of the current state of research in the field of enzyme inhibitors, which will be of interest to researchers in medicinal chemistry, biochemistry, and agriculture, as well as to anyone interested in the development of new drugs and crop protection agents. We welcome high-quality reviews or research articles for this Special Issue. The topics of this Special Issue include, but are not limited to, the following:

Drug repositioning;
Application of privileged structures in drug design;
New methods and new strategies to quickly discover drug candidates;
Proteolysis targeting chimeras (PROTACs);
Identification of inhibitors of new enzyme targets;
Recent advance in medicinal chemistry.

Prof. Dr. Fen Er Chen
Guest Editor

Dr. Shuai Wang
Guest Editor Assistant

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

new targets
new mechanisms
new strategies
drug design
PROTACs

Published Papers (5 papers)

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Research

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14 pages, 3333 KiB

Open AccessArticle

Rivastigmine–Bambuterol Hybrids as Selective Butyrylcholinesterase Inhibitors

by Jie Wu, Zekai Tan, Marco Pistolozzi and Wen Tan

Molecules 2024, 29(1), 72; https://doi.org/10.3390/molecules29010072 - 22 Dec 2023

Viewed by 798

Abstract

Selective butyrylcholinesterase inhibitors are considered promising drug candidates for the treatment of Alzheimer’s disease. In this work, one rivastigmine–bambuterol hybrid (MTR-1) and fourteen of its analogues were synthesized, purified, and characterized. In vitro cholinesterase assays showed that all the compounds were more potent inhibitors of BChE when compared to AChE. Further investigations indicated that MTR-3 (IC_50(AChE) > 100,000 nM, IC_50(BChE) = 78 nM) was the best compound in the series, showing high butyrylcholinesterase selectivity and inhibition potency, the potential to permeate the blood–brain barrier, and longer-lasting BChE inhibition than bambuterol. These compounds could be used to discover novel specific BChE inhibitors for the treatment of Alzheimer’s disease. Full article

(This article belongs to the Special Issue Synthesis and Evaluation of Bioactivity of Enzyme Inhibitors)

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13 pages, 3072 KiB

Open AccessArticle

Design, Synthesis, and Antiproliferative Activity of Selective Histone Deacetylases 6 Inhibitors Containing a Tetrahydropyridopyrimidine Scaffold

by Bin Wang, Youcai Liu, Lejing Zhang, Yajuan Wang, Zhaoxi Li and Xin Chen

Molecules 2023, 28(21), 7323; https://doi.org/10.3390/molecules28217323 - 29 Oct 2023

Cited by 1 | Viewed by 691

Abstract

The development of selective histone deacetylase 6 inhibitors (sHDAC6is) is being recognized as a therapeutic approach for cancers. In this paper, we designed a series of novel tetrahydropyridopyrimidine derivatives as sHDAC6 inhibitors. The most potent compound, 8-(2, 4-bis(3-methoxyphenyl)-5, 8-dihydropyrido [3, 4-d]pyrimidin-7(6H)-yl)-N-hydroxy-8-oxooctanamide (8f), inhibited HDAC6 with IC₅₀ of 6.4 nM, and showed > 48-fold selectivity over other subtypes. In Western blot assay, 8f elevated the levels of acetylated α-tubulin in a dose-dependent manner. In vitro, 8f inhibited RPMI-8226, HL60, and HCT116 tumor cells with IC₅₀ of 2.8, 3.20, and 3.25 μM, respectively. Moreover, 8f showed good antiproliferative activity against a panel of tumor cells. Full article

(This article belongs to the Special Issue Synthesis and Evaluation of Bioactivity of Enzyme Inhibitors)

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Review

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30 pages, 4067 KiB

Open AccessReview

Synthetic Routes and Clinical Application of Representative Small-Molecule EGFR Inhibitors for Cancer Therapy

by Ya-Tao Wang, Peng-Cheng Yang, Jing-Yi Zhang and Jin-Feng Sun

Molecules 2024, 29(7), 1448; https://doi.org/10.3390/molecules29071448 - 23 Mar 2024

Viewed by 716

Abstract

The epidermal growth factor receptor (EGFR) plays a pivotal role in cancer therapeutics, with small-molecule EGFR inhibitors emerging as significant agents in combating this disease. This review explores the synthesis and clinical utilization of EGFR inhibitors, starting with the indispensable role of EGFR in oncogenesis and emphasizing the intricate molecular aspects of the EGFR-signaling pathway. It subsequently provides information on the structural characteristics of representative small-molecule EGFR inhibitors in the clinic. The synthetic methods and associated challenges pertaining to these compounds are thoroughly examined, along with innovative strategies to overcome these obstacles. Furthermore, the review discusses the clinical applications of FDA-approved EGFR inhibitors such as erlotinib, gefitinib, afatinib, and osimertinib across various cancer types and their corresponding clinical outcomes. Additionally, it addresses the emergence of resistance mechanisms and potential counterstrategies. Taken together, this review aims to provide valuable insights for researchers, clinicians, and pharmaceutical scientists interested in comprehending the current landscape of small-molecule EGFR inhibitors. Full article

(This article belongs to the Special Issue Synthesis and Evaluation of Bioactivity of Enzyme Inhibitors)

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45 pages, 6382 KiB

Open AccessReview

Catalysts of Healing: A Symphony of Synthesis and Clinical Artistry in Small-Molecule Agents for Breast Cancer Alleviation

by Jing Hu, Bi-Yue Zhu and Zhen-Xi Niu

Molecules 2024, 29(5), 1166; https://doi.org/10.3390/molecules29051166 - 05 Mar 2024

Viewed by 906

Abstract

Breast cancer, characterized by its molecular intricacy, has witnessed a surge in targeted therapeutics owing to the rise of small-molecule drugs. These entities, derived from cutting-edge synthetic routes, often encompassing multistage reactions and chiral synthesis, target a spectrum of oncogenic pathways. Their mechanisms of action range from modulating hormone receptor signaling and inhibiting kinase activity, to impeding DNA damage repair mechanisms. Clinical applications of these drugs have resulted in enhanced patient survival rates, reduction in disease recurrence, and improved overall therapeutic indices. Notably, certain molecules have showcased efficacy in drug-resistant breast cancer phenotypes, highlighting their potential in addressing treatment challenges. The evolution and approval of small-molecule drugs have ushered in a new era for breast cancer therapeutics. Their tailored synthetic pathways and defined mechanisms of action have augmented the precision and efficacy of treatment regimens, paving the way for improved patient outcomes in the face of this pervasive malignancy. The present review embarks on a detailed exploration of small-molecule drugs that have secured regulatory approval for breast cancer treatment, emphasizing their clinical applications, synthetic pathways, and distinct mechanisms of action. Full article

(This article belongs to the Special Issue Synthesis and Evaluation of Bioactivity of Enzyme Inhibitors)

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21 pages, 6396 KiB

Open AccessReview

A Comprehensive Review of Small-Molecule Inhibitors Targeting Bruton Tyrosine Kinase: Synthetic Approaches and Clinical Applications

by Qi Zhang, Changming Wen, Lijie Zhao and Yatao Wang

Molecules 2023, 28(24), 8037; https://doi.org/10.3390/molecules28248037 - 11 Dec 2023

Viewed by 1851

Abstract

Bruton tyrosine kinase (BTK) is an essential enzyme in the signaling pathway of the B-cell receptor (BCR) and is vital for the growth and activation of B-cells. Dysfunction of BTK has been linked to different types of B-cell cancers, autoimmune conditions, and inflammatory ailments. Therefore, focusing on BTK has become a hopeful approach in the field of therapeutics. Small-molecule inhibitors of BTK have been developed to selectively inhibit its activity and disrupt B-cell signaling pathways. These inhibitors bind to the active site of BTK and prevent its phosphorylation, leading to the inhibition of downstream signaling cascades. Regulatory authorities have granted approval to treat B-cell malignancies, such as chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), with multiple small-molecule BTK inhibitors. This review offers a comprehensive analysis of the synthesis and clinical application of conventional small-molecule BTK inhibitors at various clinical stages, as well as presents promising prospects for the advancement of new small-molecule BTK inhibitors. Full article

(This article belongs to the Special Issue Synthesis and Evaluation of Bioactivity of Enzyme Inhibitors)

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