Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
7.4
4.2
Journals
Molecules
Special Issues
Design, Synthesis and Structure-Activity Relationship of Small-Molecule Inhibitors
molecules-logo
Submit to Molecules Review for Molecules Propose a Special Issue

Journal Menu

► Journal Menu

Journal Browser

► Journal Browser
share announcement

Design, Synthesis and Structure-Activity Relationship of Small-Molecule Inhibitors

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

Deadline for manuscript submissions: closed (30 September 2023) | Viewed by 12677

Special Issue Editor

Dr. Qihua Zhu

E-Mail Website
Guest Editor
Jiangsu Key Laboratory of Drug Design and Optimization, Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 211198, China
Interests: medicinal chemistry; drug design; antitumor; DNA damage repair; PROTACs

Special Issue Information

Dear Colleagues,

Small molecule inhibitors are a class of organic molecules or natural products which can bind to target proteins and reduce their biological activity. Currently, they are still the main component of most small molecule drugs in clinic. In addition, they are often used as tools in biological and pharmacological research to understand the functions of proteins and their role in normal physiology and disease pathology. Small molecule inhibitors play a significant role in medical chemistry and related subjects of pharmacy. Therefore, researchers from the pharmaceutical field and from academia always focus their efforts on identifying and developing novel and valuable small molecule inhibitors. Discovery and optimization of novel small molecule inhibitors through rational design strategies are very interesting and full of challenges and will provide more information and experience to related researchers of medicinal chemistry.

This Special Issue will focus on the latest processes and strategies in the field of designing and optimizing small molecule inhibitors. Scientists from related research fields around the world are cordially invited to contribute original research articles or reviews to this Special Issue of Molecules and present their latest work on the design, synthesis, and structure–activity relationship of small-molecule inhibitors, including selective or multiple-target small molecule inhibitors for targeting different enzymes or signal pathways, etc.

Dr. Qihua Zhu
Guest Editor

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

  • small molecule inhibitors
  • drug design
  • structure–activity relationship (SAR)
  • selective inhibitors
  • multiple target inhibitors

Published Papers (5 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Other

17 pages, 4867 KiB  
Article
Synthesis, Antioxidant, Molecular Docking and DNA Interaction Studies of Metal-Based Imine Derivatives
by Mohammad Ibrahim, Hazrat Un Nabi, Niaz Muhammad, Muhammad Ikram, Momin Khan, Musadiq Ibrahim, Abdullah F. AlAsmari, Metab Alharbi and Abdulrahman Alshammari
Molecules 2023, 28(15), 5926; https://doi.org/10.3390/molecules28155926 - 7 Aug 2023
Cited by 4 | Viewed by 1568
Abstract
Currently, numerous ongoing studies are investigating the interaction of free radicals with biological systems, such as lipids, DNA and protein. In the present work, synthesis, characterization, antioxidant, DNA binding and molecular docking studies of Schiff base ligand and its Ni(II), Co(II), Cu(II) and [...] Read more.
Currently, numerous ongoing studies are investigating the interaction of free radicals with biological systems, such as lipids, DNA and protein. In the present work, synthesis, characterization, antioxidant, DNA binding and molecular docking studies of Schiff base ligand and its Ni(II), Co(II), Cu(II) and Zn(II) were evaluated. The metal complexes have shown significant dose-dependent antioxidant activities higher than those of the free ligand but lesser than those of the standard antioxidant, ascorbic acid. The DNA binding constants (Kb) were found in the order Zn(pimp)2 {9.118 × 105 M−1} > H-pimp {3.487 × 105 M−1} > Co(pimp)2 {3.090 × 105 M−1} > Ni(pimp)2 {1.858 × 105 M−1} > Cu(pimp)2 {1.367 × 105 M−1}. Binding constants (Kb) values calculated from the molecular docking analysis were found to be in close agreement with the experimental results. The obtained results indicate the importance of synthesis complexes as a source of synthetic antioxidants and anticancer drugs. Full article
(This article belongs to the Special Issue Design, Synthesis and Structure-Activity Relationship of Small-Molecule Inhibitors)
►▼ Show Figures

Graphical abstract

20 pages, 9007 KiB  
Article
Design, Synthesis, and Biological Evaluation of Potent and Selective Inhibitors of Ataxia Telangiectasia Mutated and Rad3-Related (ATR) Kinase for the Efficient Treatment of Cancer
by Jialu Shao, Lei Huang, Wenwen Lai, Yi Zou and Qihua Zhu
Molecules 2023, 28(11), 4521; https://doi.org/10.3390/molecules28114521 - 2 Jun 2023
Viewed by 1900
Abstract
Ataxia telangiectasia mutated and Rad3-related (ATR), a vital member of the phosphatidylinositol 3-kinase-related kinase (PIKK) family, plays a critical role in the DNA damage response (DDR). Tumor cells with a loss of DDR function or defects in the ataxia telangiectasia mutated (ATM) gene [...] Read more.
Ataxia telangiectasia mutated and Rad3-related (ATR), a vital member of the phosphatidylinositol 3-kinase-related kinase (PIKK) family, plays a critical role in the DNA damage response (DDR). Tumor cells with a loss of DDR function or defects in the ataxia telangiectasia mutated (ATM) gene are generally more dependent on ATR for survival, suggesting that ATR is an attractive anticancer drug target based on its synthetic lethality. Herein, we present a potent and highly selective ATR inhibitor, ZH-12 (IC50 = 0.0068 μM). It showed potent antitumor activity as a single agent or in combination with cisplatin in the human colorectal adenocarcinoma LoVo tumor xenograft mouse model. Overall, ZH-12 may be a promising ATR inhibitor based on the principle of synthetic lethality and deserves further in-depth study. Full article
(This article belongs to the Special Issue Design, Synthesis and Structure-Activity Relationship of Small-Molecule Inhibitors)
►▼ Show Figures

Figure 1

18 pages, 4180 KiB  
Article
Systematic Studies on Anti-Cancer Evaluation of Stilbene and Dibenzo[b,f]oxepine Derivatives
by Filip Borys, Piotr Tobiasz, Marcin Poterała, Hanna Fabczak, Hanna Krawczyk and Ewa Joachimiak
Molecules 2023, 28(8), 3558; https://doi.org/10.3390/molecules28083558 - 18 Apr 2023
Cited by 4 | Viewed by 1612
Abstract
Cancer is one of the most common causes of human death worldwide; thus, numerous therapies, including chemotherapy, have been and are being continuously developed. In cancer cells, an aberrant mitotic spindle—a microtubule-based structure necessary for the equal splitting of genetic material between daughter [...] Read more.
Cancer is one of the most common causes of human death worldwide; thus, numerous therapies, including chemotherapy, have been and are being continuously developed. In cancer cells, an aberrant mitotic spindle—a microtubule-based structure necessary for the equal splitting of genetic material between daughter cells—leads to genetic instability, one of the hallmarks of cancer. Thus, the building block of microtubules, tubulin, which is a heterodimer formed from α- and β-tubulin proteins, is a useful target in anti-cancer research. The surface of tubulin forms several pockets, i.e., sites that can bind factors that affect microtubules’ stability. Colchicine pockets accommodate agents that induce microtubule depolymerization and, in contrast to factors that bind to other tubulin pockets, overcome multi-drug resistance. Therefore, colchicine-pocket-binding agents are of interest as anti-cancer drugs. Among the various colchicine-site-binding compounds, stilbenoids and their derivatives have been extensively studied. Herein, we report systematic studies on the antiproliferative activity of selected stilbenes and oxepine derivatives against two cancer cell lines—HCT116 and MCF-7—and two normal cell lines—HEK293 and HDF-A. The results of molecular modeling, antiproliferative activity, and immunofluorescence analyses revealed that compounds 1a, 1c, 1d, 1i, 2i, 2j, and 3h were the most cytotoxic and acted by interacting with tubulin heterodimers, leading to the disruption of the microtubular cytoskeleton. Full article
(This article belongs to the Special Issue Design, Synthesis and Structure-Activity Relationship of Small-Molecule Inhibitors)
►▼ Show Figures

Figure 1

24 pages, 6939 KiB  
Article
Design, Synthesis and Biological Evaluation of Novel and Potent Protein Arginine Methyltransferases 5 Inhibitors for Cancer Therapy
by Yixuan Tang, Shihui Huang, Xingxing Chen, Junzhang Huang, Qianwen Lin, Lei Huang, Shuping Wang, Qihua Zhu, Yungen Xu and Yi Zou
Molecules 2022, 27(19), 6637; https://doi.org/10.3390/molecules27196637 - 6 Oct 2022
Cited by 3 | Viewed by 2096
Abstract
Protein arginine methyltransferases 5 (PRMT5) is a clinically promising epigenetic target that is upregulated in a variety of tumors. Currently, there are several PRMT5 inhibitors under preclinical or clinical development, however the established clinical inhibitors show favorable toxicity. Thus, it remains an unmet [...] Read more.
Protein arginine methyltransferases 5 (PRMT5) is a clinically promising epigenetic target that is upregulated in a variety of tumors. Currently, there are several PRMT5 inhibitors under preclinical or clinical development, however the established clinical inhibitors show favorable toxicity. Thus, it remains an unmet need to discover novel and structurally diverse PRMT5 inhibitors with characterized therapeutic utility. Herein, a series of tetrahydroisoquinoline (THIQ) derivatives were designed and synthesized as PRMT5 inhibitors using GSK-3326595 as the lead compound. Among them, compound 20 (IC50: 4.2 nM) exhibits more potent PRMT5 inhibitory activity than GSK-3326595 (IC50: 9.2 nM). In addition, compound 20 shows high anti-proliferative effects on MV-4-11 and MDA-MB-468 tumor cells and low cytotoxicity on AML-12 hepatocytes. Furthermore, compound 20 possesses acceptable pharmacokinetic profiles and displays considerable in vivo antitumor efficacy in a MV-4-11 xenograft model. Taken together, compound 20 is an antitumor compound worthy of further study. Full article
(This article belongs to the Special Issue Design, Synthesis and Structure-Activity Relationship of Small-Molecule Inhibitors)
►▼ Show Figures

Graphical abstract

Other

Jump to: Research

38 pages, 12756 KiB  
Systematic Review
An Insight into the Medicinal Chemistry Perspective of Macrocyclic Derivatives with Antitumor Activity: A Systematic Review
by Yan Liang, Ru Fang and Qiu Rao
Molecules 2022, 27(9), 2837; https://doi.org/10.3390/molecules27092837 - 29 Apr 2022
Cited by 12 | Viewed by 4458
Abstract
The profound pharmacological properties of macrocyclic compounds have led to their development as drugs. In conformationally pre-organized ring structures, the multiple functions and stereochemical complexity provided by the macrocycle result in high affinity and selectivity of protein targets while maintaining sufficient bioavailability to [...] Read more.
The profound pharmacological properties of macrocyclic compounds have led to their development as drugs. In conformationally pre-organized ring structures, the multiple functions and stereochemical complexity provided by the macrocycle result in high affinity and selectivity of protein targets while maintaining sufficient bioavailability to reach intracellular locations. Therefore, the construction of macrocycles is an ideal choice to solve the problem of “undruggable” targets. Inspection of 68 macrocyclic drugs on the market showed that 10 of them were used to treat cancer, but this structural class still has been poorly explored within drug discovery. This perspective considers the macrocyclic compounds used for anti-tumor with different targets, their advantages and disadvantages, and the various synthetic methods of them. Full article
(This article belongs to the Special Issue Design, Synthesis and Structure-Activity Relationship of Small-Molecule Inhibitors)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-5
Back to TopTop