Molecules Containing Cyclobutyl Fragments as Therapeutic Tools: A Review on Cyclobutyl Drugs

Abstract: In recent years, cyclobutyl has become ever more influential in the field of drug design. Its unique four-membered ring structure is not only a useful intermediate for the synthesis of biomedical candidate materials, but also an indispensable framework for drug design and application. According to the therapeutic field, cyclobutyl drugs are roughly divided into tumor and cancer drugs, nervous system drugs, analgesics, antiviral drugs, and gastrointestinal drugs. Among them, platinum-based anticancer drugs containing cyclobutyl fragments have achieved remarkable success in the treatment of cancer, bringing new hope for the development of more cyclobutyl drugs. This article provides details of the research progress of the structure types, structure-activity relationships, targets, and mechanisms of cyclobutyl drugs that have been on the market or are in the clinical stage, and provides ideas for the discovery and synthesis of novel cyclobutyl-containing drugs.

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Recent Advances towards Drug Design Targeting the Protease of 2019 novel coronavirus (2019-nCoV)

Current Medicinal Chemistry ◽

10.2174/0929867327666201027153617 ◽

2020 ◽

Vol 27 ◽

Author(s):

Sehrish Bano ◽

Abdul Hameed ◽

Mariya Al-Rashida ◽

Shafia Iftikhar ◽

Jamshed Iqbal

Keyword(s):

Drug Design ◽

Rna Polymerase ◽

Drug Targets ◽

Antiviral Agents ◽

Structural Features ◽

Antiviral Drugs ◽

Rna Dependent Rna Polymerase ◽

Mortality And Morbidity ◽

Functional Relationships ◽

Novel Coronavirus

Background: The 2019 novel coronavirus (2019-nCoV), also known as coronavirus 2 (SARS-CoV-2) acute respiratory syndrome has recently emerged and continued to spread rapidly with high level of mortality and morbidity rates. Currently, no efficacious therapy is available to relieve coronavirus infections. As new drug design and development takes much time, there is a possibility to find an effective treatment from existing antiviral agents. Objective: In this case, there is a need to find out the relationship between possible drug targets and mechanism of action of antiviral drugs. This review discusses about the efforts to develop drug from known or new molecules. Methods: Viruses usually have two structural integrities, proteins and nucleic acids, both of which can be possible drug targets. Herein, we systemically discuss the structural-functional relationships of the spike, 3-chymotrypsin-like protease (3CLpro), papain like protease (PLpro) and RNA-dependent RNA polymerase (RdRp), as these are prominent structural features of corona virus. Certain antiviral drugs such as Remdesivir are RNA dependent RNA polymerase inhibitor. It has the ability to terminate RNA replication by inhibiting ATP. Results: It is reported that ATP is involved in synthesis of coronavirus non-structural proteins from 3CLpro and PLpro. Similarly, mechanisms of action of many other antiviral agents has been discussed in this review. It will provide new insights into the mechanism of inhibition, and let us develop new therapeutic antiviral approaches against novel SARS-CoV-2 coronavirus. Conclusion: In conclusion, this review summarizes recent progress in developing protease inhibitors for SARS-CoV-2.

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Turning Fear of Boron Toxicity into Boron-containing Drug Design

Current Medicinal Chemistry ◽

10.2174/0929867326666190327154954 ◽

2019 ◽

Vol 26 (26) ◽

pp. 5005-5018 ◽

Cited By ~ 1

Author(s):

Marvin A. Soriano-Ursúa ◽

Eunice D. Farfán-García ◽

Simonetta Geninatti-Crich

Keyword(s):

Drug Design ◽

Qualitative Content Analysis ◽

Biological Action ◽

Research Literature ◽

Bibliographic Databases ◽

Boron Toxicity ◽

Withdrawal Period ◽

Analysis Methodology ◽

Structure Activity ◽

Toxicological Data

Background: Despite the historical employment of boron-containing compounds (BCCs) with medicinal purposes, the reported cases of BCC toxicity in humans during the twentieth-century drived us towards a “boron-withdrawal” period. Fortunately, the use of boric acid for specific purposes remains, and the discovery of natural BCCs with biological action attractive for therapeutic purposes as well as the introduction of some new BCCs for clinical use has reactivated the interest in studying the properties of these BCCs. Methods: We carried out a structured search of bibliographic databases for scientific peerreviewed research literature regarding boron toxicity and linked that information to that of BCCs in drug design and development. A deductive qualitative content analysis methodology was applied to analyse the interventions and findings of the included studies using a theoretical outline. Results: This review recapitulates the following on a timeline: the boron uses in medicine, the data known about the toxicological profiles of some BCCs, the pharmacological properties of some BCCs that are employed in cancer and infectious disease therapies, and the known properties of BCCs recently introduced into clinical assays as well as the identification of their structure-activity relationships for toxicity and therapeutic use. Then, we discuss the use of new approaches taking advantage of some toxicological data to identify potent and efficient BCCs for prevention and therapy while limiting their toxic effects. Conclusion: Data for boron toxicity can be strategically used for boron-containing drug design.

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Recent Design and Structure-Activity Relationship Studies on Modifications of DHFR Inhibitors as Anticancer Agents

Current Medicinal Chemistry ◽

10.2174/0929867326666191016151018 ◽

2019 ◽

Vol 26 ◽

Cited By ~ 1

Author(s):

Agnieszka Wróbel ◽

Danuta Drozdowska

Keyword(s):

Anticancer Activity ◽

Anticancer Drugs ◽

Anticancer Agents ◽

Physicochemical Characterization ◽

Structure Activity Relationship ◽

Activity Relationship ◽

Biological Research ◽

Structure Activity ◽

Dhfr Inhibitors

Background: Dihydrofolate reductase (DHFR) has been known for decades as a molecular target for antibacterial, antifungal and anti-malarial treatments. This enzyme is becoming increasingly important in the design of new anticancer drugs, which is confirmed by numerous studies including modelling, synthesis and in vitro biological research. This review aims to present and discuss some remarkable recent advances on the research of new DHFR inhibitors with potential anticancer activity. Methods: The scientific literature of the last decade on the different types of DHFR inhibitors has been searched. The studies on design, synthesis and investigation structure-activity relationship were summarized and divided into several subsections depending on the leading molecule and its structural modification. Various methods of synthesis, potential anticancer activity and possible practical applications as DHFR inhibitors of new chemical compounds were described and discussed. Results: This review presents the current state of knowledge on the modification of known DHFR inhibitors and the structures and searching for over eighty new molecules, designed as potential anticancer drugs. In addition, DHFR inhibitors acting on thymidylate synthase (TS), carbon anhydrase (CA) and even DNA-binding are presented in this paper. Conclusion: Thorough physicochemical characterization and biological investigations it is possible to understand structure-activity relationship of DHFR inhibitors. This will enable even better design and synthesis of active compounds, which would have the expected mechanism of action and the desired activity.

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Application of Machine Learning Approaches for the Design and Study of Anticancer Drugs

Current Drug Targets ◽

10.2174/1389450119666180809122244 ◽

2019 ◽

Vol 20 (5) ◽

pp. 488-500 ◽

Cited By ~ 6

Author(s):

Yan Hu ◽

Yi Lu ◽

Shuo Wang ◽

Mengying Zhang ◽

Xiaosheng Qu ◽

...

Keyword(s):

Machine Learning ◽

Drug Design ◽

Anticancer Drugs ◽

Nearest Neighbor ◽

Cost Effective ◽

Support Vector ◽

Learning Approaches ◽

K Nearest Neighbor ◽

Activity Prediction ◽

Linear Discriminant

Background: Globally the number of cancer patients and deaths are continuing to increase yearly, and cancer has, therefore, become one of the world's highest causes of morbidity and mortality. In recent years, the study of anticancer drugs has become one of the most popular medical topics. Objective: In this review, in order to study the application of machine learning in predicting anticancer drugs activity, some machine learning approaches such as Linear Discriminant Analysis (LDA), Principal components analysis (PCA), Support Vector Machine (SVM), Random forest (RF), k-Nearest Neighbor (kNN), and Naïve Bayes (NB) were selected, and the examples of their applications in anticancer drugs design are listed. Results: Machine learning contributes a lot to anticancer drugs design and helps researchers by saving time and is cost effective. However, it can only be an assisting tool for drug design. Conclusion: This paper introduces the application of machine learning approaches in anticancer drug design. Many examples of success in identification and prediction in the area of anticancer drugs activity prediction are discussed, and the anticancer drugs research is still in active progress. Moreover, the merits of some web servers related to anticancer drugs are mentioned.

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Therapeutic Journey of 5-Pyrazolones as a Versatile Scaffold: A Review

Mini-Reviews in Medicinal Chemistry ◽

10.2174/1389557521999210101224058 ◽

2021 ◽

Vol 21 ◽

Author(s):

Ravinder Sharma ◽

Pooja A. Chawla ◽

Viney Chawla ◽

Rajeev Verma ◽

Nandita Nawal ◽

...

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Protease Inhibitor ◽

Medicinal Chemistry ◽

Membered Ring ◽

Present Review ◽

Biological Profile ◽

3C Protease ◽

Structure Activity ◽

Derivatives Of ◽

Heterocyclic Moiety

Abstract: A sizeable proportion of currently marketed drugs come from heterocycles. The heterocyclic moiety 5-pyrazolone is well known five membered ring containing nitrogen. Derivatives of this wonder nucleus have exhibited activities as diverse as antimicrobial, anti-inflammatory, analgesic, antidepressant, anticonvulsant, antidiabetic, antihyperlipidemic, antiviral, antitubercular, antioxidant, anticancer and antiviral including action against severe acute respiratory syndrome (SARS) or 3C protease inhibitor. A number of drugs based on this motif have already made it to the market. Standard texts and literature on medicinal chemistry cite different approaches for the synthesis of 5-pyrazolones. The present review provides an insight view to 5-pyrazolone synthesis, their biological profile and structure activity relationship studies.

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Editorial [Hot Topic: QSAR Models for Computer-Aided Drug Design and Molecular Docking for Disorders of the Central Nervous System and Other Diseases]

Current Topics in Medicinal Chemistry ◽

10.2174/1568026611209061731 ◽

2012 ◽

Vol 12 (16) ◽

pp. 1731-1733 ◽

Cited By ~ 2

Author(s):

Francisco Prado-Prado ◽

Xerardo Garcia-Mera

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Molecular Docking ◽

Drug Design ◽

Computer Aided Drug Design ◽

Computer Aided ◽

Qsar Models ◽

The Central Nervous System

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Research Progress of Synthesis and Structure-activity Relationship Studies on Sulfonium-type α-glucosidase Inhibitors Isolated from Salacia Genus Plants

Mini-Reviews in Organic Chemistry ◽

10.2174/1570193x11310020004 ◽

2013 ◽

Vol 10 (2) ◽

pp. 141-159 ◽

Cited By ~ 17

Author(s):

Weijia Xie ◽

Genzoh Tanabe ◽

Jinyi Xu ◽

Xiaoming Wu ◽

Toshio Morikawa ◽

...

Keyword(s):

Structure Activity Relationship ◽

Research Progress ◽

Activity Relationship ◽

Structure Activity ◽

Glucosidase Inhibitors

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Ethanolamine: A Potential Promoiety with Additional Effects in the Brain

CNS & Neurological Disorders - Drug Targets ◽

10.2174/1871527319999201211204645 ◽

2020 ◽

Vol 19 ◽

Author(s):

Asfree Gwanyanya ◽

Christie Nicole Godsmark ◽

Roisin Kelly-Laubscher

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Drug Design ◽

Cell Signaling ◽

Blood Brain Barrier ◽

Brain Barrier ◽

The Central Nervous System ◽

Bioactive Molecule ◽

Positive Functions ◽

The Brain

Abstract: Ethanolamine is a bioactive molecule found in several cells, including those in the central nervous system (CNS). In the brain, ethanolamine and ethanolamine-related molecules have emerged as prodrug moieties that can promote drug movement across the blood-brain barrier. This improvement in the ability to target drugs to the brain may also mean that in the process ethanolamine concentrations in the brain are increased enough for ethanolamine to exert its own neurological ac-tions. Ethanolamine and its associated products have various positive functions ranging from cell signaling to molecular storage, and alterations in their levels have been linked to neurodegenerative conditions such as Alzheimer’s disease. This mini-review focuses on the effects of ethanolamine in the CNS and highlights the possible implications of these effects for drug design.

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A review on the production, structure, bioactivities and applications of Tremella polysaccharides

International Journal of Immunopathology and Pharmacology ◽

10.1177/20587384211000541 ◽

2021 ◽

Vol 35 ◽

pp. 205873842110005

Author(s):

Xia Ma ◽

Meng Yang ◽

Yan He ◽

Chuntao Zhai ◽

Chengliang Li

Keyword(s):

Biologically Active ◽

Research Progress ◽

Research Trend ◽

Production Structure ◽

Health States ◽

Preparation Methods ◽

The Past ◽

Structure Activity ◽

Relationship Of ◽

Active Natural

Tremella polysaccharide is known to be structurally unique and biologically active natural products, abundant and versatile in activities and applications in food industry, daily chemical industry and medicine industry. In order to improve the industrialisation of Tremella polysaccharide, the limitations of preparation and structure-activity relationship of Tremella polysaccharide were reviewed in this paper. The research progress of Tremella polysaccharide in the past 20 years was summarized from the sources, preparation methods, molecular structure, activity and application, and the research trend in the future was also prospected. The application prospect of Tremella polysaccharide in against multiple sub-health states was worth expecting.

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