Submit to Pharmaceuticals Review for Pharmaceuticals Propose a Special Issue

Journal Browser

► Journal Browser

Feature Reviews in Medicinal Chemistry

Special Issue Editors
Special Issue Information
Keywords
Published Papers

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: closed (31 October 2023) | Viewed by 33299

Share This Special Issue

Special Issue Editor

Prof. Dr. Mary J. Meegan

E-Mail Website
Guest Editor

Trinity Biomedical Sciences Institute, School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, 152−160 Pearse Street, Dublin 2 D02 R590, Ireland
Interests: anticancer drug design; breast cancer; novel antioestrogens; tubulin targeting agents; azetidinones; antioestrogen–drug conjugates; oestrogen receptor; Burkitt's lymphoma; chronic lymphocytic leukaemia
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The Medicinal Chemistry section of Pharmaceuticals invites high-quality reviews contributing towards our understanding of the relationship between the molecular structure and biological activity of drug molecules. The relevant topics in this Special Issue include the discovery, design and synthesis of biologically active compounds, together with the interpretation of their structure–activity relationships and mechanism of action at the molecular level. Our aim is to include outstanding reviews covering all aspects of small molecules as clinical drug candidates, e.g., drug discovery and design, combinatorial chemistry, molecular modelling and bioinformatics. Suitable topics also include novel synthetic routes for drug candidates, leading discovery and optimization methods, structure-based drug design, crystal structure analysis and drug metabolism. In addition, the identification and validation of novel drug targets, high-throughput screening methodologies, virtual screening techniques, database mining and machine learning in drug discovery are included in the scope of topics for these reviews. Chemical biology and structural studies which investigate chemical probes and the molecular recognition processes identified in the action of biologically active molecules are particularly welcome. Reviews which describe novel strategies and methodologies with relevant applications in chemical biology and medicinal chemistry are also welcome.

Submissions to the Special Issue must include a cover letter indicating the novelty of the review article in relation to reviews published in the literature. A 20% discount will be applied to the Article Processing Charges (APCs).

Prof. Dr. Mary J. Meegan
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. Pharmaceuticals is an international peer-reviewed open access monthly 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 2900 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

drug discovery, design and synthesis
structure–activity relationships
molecular modelling
novel drug targets
high-throughput screening
drug metabolism
drug analytical methods

Published Papers (11 papers)

Download All Papers

Review

57 pages, 8862 KiB

Open AccessReview

Advancements in Phosphodiesterase 5 Inhibitors: Unveiling Present and Future Perspectives

by Ahmed K. ElHady, Dalia S. El-Gamil, Mohammad Abdel-Halim and Ashraf H. Abadi

Pharmaceuticals 2023, 16(9), 1266; https://doi.org/10.3390/ph16091266 - 06 Sep 2023

Cited by 1 | Viewed by 3167

Abstract

Phosphodiesterase 5 (PDE5) inhibitors presented themselves as important players in the nitric oxide/cGMP pathway, thus exerting a profound impact on various physiological and pathological processes. Beyond their well-known efficacy in treating male erectile dysfunction (ED) and pulmonary arterial hypertension (PAH), a plethora of studies have unveiled their significance in the treatment of a myriad of other diseases, including cognitive functions, heart failure, multiple drug resistance in cancer therapy, immune diseases, systemic sclerosis and others. This comprehensive review aims to provide an updated assessment of the crucial role played by PDE5 inhibitors (PDE5-Is) as disease-modifying agents taking their limiting side effects into consideration. From a medicinal chemistry and drug discovery perspective, the published PDE5-Is over the last 10 years and their binding characteristics are systemically discussed, and advancement in properties is exposed. A persistent challenge encountered with these agents lies in their limited isozyme selectivity; considering this obstacle, this review also highlights the breakthrough development of the recently reported PDE5 allosteric inhibitors, which exhibit an unparalleled level of selectivity that was rarely achievable by competitive inhibitors. The implications and potential impact of these novel allosteric inhibitors are meticulously explored. Additionally, the concept of multi-targeted ligands is critically evaluated in relation to PDE5-Is by inspecting the broader spectrum of their molecular interactions and effects. The objective of this review is to provide insight into the design of potent, selective PDE5-Is and an overview of their biological function, limitations, challenges, therapeutic potentials, undergoing clinical trials, future prospects and emerging uses, thus guiding upcoming endeavors in both academia and industry within this domain. Full article

(This article belongs to the Special Issue Feature Reviews in Medicinal Chemistry)

► Show Figures

Figure 1

26 pages, 6745 KiB

Open AccessReview

Bisindolyl Maleimides and Indolylmaleimide Derivatives—A Review of Their Synthesis and Bioactivity

by Louise N. Cooney, Kevin D. O’Shea, Hannah J. Winfield, Michael M. Cahill, Larry T. Pierce and Florence O. McCarthy

Pharmaceuticals 2023, 16(9), 1191; https://doi.org/10.3390/ph16091191 - 22 Aug 2023

Viewed by 1092

Abstract

The evolution of bisindolyl maleimides and indolyl maleimide derivatives and their unique biological activities have stimulated great interest in medicinal chemistry programs. Bisindolylmaleimide (BIM)-type compounds arise from natural sources such as arcyriarubin and are biosynthetically related to indolocarbazoles. BIMs are commonly the immediate synthetic precursors of indolocarbazoles, lacking a central bond between the two aromatic units and making them more flexible and drug-like. Synthetic endeavours within this class of compounds are broad and have led to the development of both remarkably potent and selective protein kinase inhibitors. Clinical BIM examples include ruboxistaurin and enzastaurin, which are highly active inhibitors of protein kinase C-β. While BIMs are widely recognised as protein kinase inhibitors, other modes of activity have been reported, including the inhibition of calcium signalling and antimicrobial activity. Critically, structural differences can be used to exploit new bioactivity and therefore it is imperative to discover new chemical entities to address new targets. BIMs can be highly functionalised or chemically manipulated, which provides the opportunity to generate new derivatives with unique biological profiles. This review will collate new synthetic approaches to BIM-type compounds and their associated bioactivities with a focus on clinical applications. Full article

(This article belongs to the Special Issue Feature Reviews in Medicinal Chemistry)

► Show Figures

Figure 1

22 pages, 1174 KiB

Open AccessReview

Treating Epilepsy with Natural Products: Nonsense or Possibility?

by Milan Malaník, Marie Čulenová, Alice Sychrová, Adrianna Skiba, Krystyna Skalicka-Woźniak and Karel Šmejkal

Pharmaceuticals 2023, 16(8), 1061; https://doi.org/10.3390/ph16081061 - 26 Jul 2023

Viewed by 2322

Abstract

Epilepsy is a neurological disease characterized by recurrent seizures that can lead to uncontrollable muscle twitching, changes in sensitivity to sensory perceptions, and disorders of consciousness. Although modern medicine has effective antiepileptic drugs, the need for accessible and cost-effective medication is urgent, and products derived from plants could offer a solution. For this review, we have focused on natural compounds that have shown anticonvulsant activity in in vivo models of epilepsy at relevant doses. In some cases, the effects have been confirmed by clinical data. The results of our search are summarized in tables according to their molecular targets. We have critically evaluated the data we present, identified the most promising therapeutic candidates, and discussed these in the text. Their perspectives are supported by both pharmacokinetic properties and potential interactions. This review is intended to serve as a basis for future research into epilepsy and related disorders. Full article

(This article belongs to the Special Issue Feature Reviews in Medicinal Chemistry)

► Show Figures

Figure 1

31 pages, 14193 KiB

Open AccessReview

Targeting Metalloenzymes: The “Achilles’ Heel” of Viruses and Parasites

by Dimitrios Moianos, Georgia-Myrto Prifti, Maria Makri and Grigoris Zoidis

Pharmaceuticals 2023, 16(6), 901; https://doi.org/10.3390/ph16060901 - 19 Jun 2023

Cited by 3 | Viewed by 1551

Abstract

Metalloenzymes are central to the regulation of a wide range of essential viral and parasitic functions, including protein degradation, nucleic acid modification, and many others. Given the impact of infectious diseases on human health, inhibiting metalloenzymes offers an attractive approach to disease therapy. Metal-chelating agents have been expansively studied as antivirals and antiparasitics, resulting in important classes of metal-dependent enzyme inhibitors. This review provides the recent advances in targeting the metalloenzymes of viruses and parasites that impose a significant burden on global public health, including influenza A and B, hepatitis B and C, and human immunodeficiency viruses as well as Trypanosoma brucei and Trypanosoma cruzi. Full article

(This article belongs to the Special Issue Feature Reviews in Medicinal Chemistry)

► Show Figures

Graphical abstract

22 pages, 2851 KiB

Open AccessFeature PaperReview

A Tale of Two Proteases: M^Pro and TMPRSS2 as Targets for COVID-19 Therapies

by Barbara Farkaš, Marco Minneci, Matas Misevicius and Isabel Rozas

Pharmaceuticals 2023, 16(6), 834; https://doi.org/10.3390/ph16060834 - 02 Jun 2023

Cited by 1 | Viewed by 1805

Abstract

Considering the importance of the 2019 outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) resulting in the coronavirus disease 2019 (COVID-19) pandemic, an overview of two proteases that play an important role in the infection by SARS-CoV-2, the main protease of SARS-CoV-2 (M^Pro) and the host transmembrane protease serine 2 (TMPRSS2), is presented in this review. After summarising the viral replication cycle to identify the relevance of these proteases, the therapeutic agents already approved are presented. Then, this review discusses some of the most recently reported inhibitors first for the viral M^Pro and next for the host TMPRSS2 explaining the mechanism of action of each protease. Afterward, some computational approaches to design novel M^Pro and TMPRSS2 inhibitors are presented, also describing the corresponding crystallographic structures reported so far. Finally, a brief discussion on a few reports found some dual-action inhibitors for both proteases is given. This review provides an overview of two proteases of different origins (viral and human host) that have become important targets for the development of antiviral agents to treat COVID-19. Full article

(This article belongs to the Special Issue Feature Reviews in Medicinal Chemistry)

► Show Figures

Graphical abstract

16 pages, 1038 KiB

Open AccessReview

The STAT3-Regulated Autophagy Pathway in Glioblastoma

by Ronald Nicholas Laribee, Andrew B. Boucher, Saivikram Madireddy and Lawrence M. Pfeffer

Pharmaceuticals 2023, 16(5), 671; https://doi.org/10.3390/ph16050671 - 29 Apr 2023

Cited by 4 | Viewed by 2185

Abstract

Glioblastoma (GBM) is the most common primary brain malignancy in adults with a dismal prognosis. Despite advances in genomic analysis and surgical technique and the development of targeted therapeutics, most treatment options are ineffective and mainly palliative. Autophagy is a form of cellular self-digestion with the goal of recycling intracellular components to maintain cell metabolism. Here, we describe some recent findings that suggest GBM tumors are more sensitive to the excessive overactivation of autophagy leading to autophagy-dependent cell death. GBM cancer stem cells (GSCs) are a subset of the GBM tumor population that play critical roles in tumor formation and progression, metastasis, and relapse, and they are inherently resistant to most therapeutic strategies. Evidence suggests that GSCs are able to adapt to a tumor microenvironment of hypoxia, acidosis, and lack of nutrients. These findings have suggested that autophagy may promote and maintain the stem-like state of GSCs as well as their resistance to cancer treatment. However, autophagy is a double-edged sword and may have anti-tumor properties under certain conditions. The role of the STAT3 transcription factor in autophagy is also described. These findings provide the basis for future research aimed at targeting the autophagy-dependent pathway to overcome the inherent therapeutic resistance of GBM in general and to specifically target the highly therapy-resistant GSC population through autophagy regulation. Full article

(This article belongs to the Special Issue Feature Reviews in Medicinal Chemistry)

► Show Figures

Figure 1

30 pages, 4498 KiB

Open AccessReview

Synthetic Methodologies and Therapeutic Potential of Indole-3-Carbinol (I3C) and Its Derivatives

by Federica Centofanti, Alessandro Buono, Michele Verboni, Carlo Tomino, Simone Lucarini, Andrea Duranti, Pier Paolo Pandolfi and Giuseppe Novelli

Pharmaceuticals 2023, 16(2), 240; https://doi.org/10.3390/ph16020240 - 05 Feb 2023

Cited by 5 | Viewed by 3268

Abstract

Indole-3-carbinol (I3C) is a natural product contained in vegetables belonging to the Brassicaceae family and has been studied in recent decades for its biological and pharmacological properties. Herein, we will analyze: (1) the biosynthetic processes and synthetic procedures through which I3C and its main derivatives have been obtained; (2) the characteristics that lead to believe that both I3C and its derivatives are responsible for several important activities—in particular, antitumor and antiviral, through insights concerning in vitro assays and in vivo tests; (3) the mechanisms of action of the most important compounds considered; (4) the potential social impact that the enhancement of the discussed molecules can have in the prevention and treatment of the pathologies’ examined field—first of all, those related to respiratory tract disorders and cancer. Full article

(This article belongs to the Special Issue Feature Reviews in Medicinal Chemistry)

► Show Figures

Figure 1

41 pages, 5128 KiB

Open AccessReview

Cyclooxygenase-2 (COX-2) as a Target of Anticancer Agents: A Review of Novel Synthesized Scaffolds Having Anticancer and COX-2 Inhibitory Potentialities

by Noor ul Amin Mohsin, Sana Aslam, Matloob Ahmad, Muhammad Irfan, Sami A. Al-Hussain and Magdi E. A. Zaki

Pharmaceuticals 2022, 15(12), 1471; https://doi.org/10.3390/ph15121471 - 26 Nov 2022

Cited by 12 | Viewed by 2470

Abstract

Cancer is a serious threat to human beings and is the second-largest cause of death all over the globe. Chemotherapy is one of the most common treatments for cancer; however, drug resistance and severe adverse effects are major problems associated with anticancer therapy. New compounds with multi-target inhibitory properties are targeted to surmount these challenges. Cyclooxygenase-2 (COX-2) is overexpressed in cancers of the pancreas, breast, colorectal, stomach, and lung carcinoma. Therefore, COX-2 is considered a significant target for the synthesis of new anticancer agents. This review discusses the biological activity of recently prepared dual anticancer and COX-2 inhibitory agents. The most important intermolecular interactions with the COX-2 enzyme have also been presented. Analysis of these agents in the active area of the COX-2 enzyme could guide the introduction of new lead compounds with extreme selectivity and minor side effects. Full article

(This article belongs to the Special Issue Feature Reviews in Medicinal Chemistry)

► Show Figures

Figure 1

43 pages, 14709 KiB

Open AccessReview

New Antifungal Agents with Azole Moieties

by Melissa Martins Teixeira, Diogo Teixeira Carvalho, Emília Sousa and Eugénia Pinto

Pharmaceuticals 2022, 15(11), 1427; https://doi.org/10.3390/ph15111427 - 17 Nov 2022

Cited by 16 | Viewed by 7641

Abstract

Fungal conditions affect a multitude of people worldwide, leading to increased hospitalization and mortality rates, and the need for novel antifungals is emerging with the rise of resistance and immunocompromised patients. Continuous use of azole drugs, which act by inhibiting the fungal CYP51, involved in the synthesis of ergosterol, essential to the fungal cell membrane, has enhanced the resistance and tolerance of some fungal strains to treatment, thereby limiting the arsenal of available drugs. The goal of this review is to gather literature information on new promising azole developments in clinical trials, with in vitro and in vivo results against fungal strains, and complementary assays, such as toxicity, susceptibility assays, docking studies, among others. Several molecules are reviewed as novel azole structures in clinical trials and with recent/imminent approvals, as well as other innovative molecules with promising antifungal activity. Structure–activity relationship (SAR) studies are displayed whenever possible. The azole moiety is brought over as a privileged structure, with multiple different compounds emerging with distinct pharmacophores and SAR. Particularly, 1,2,3-triazole natural product conjugates emerged in the last years, presenting promising antifungal activity and a broad spectrum against various fungi. Full article

(This article belongs to the Special Issue Feature Reviews in Medicinal Chemistry)

► Show Figures

Figure 1

35 pages, 9987 KiB

Open AccessReview

Chalcone: A Promising Bioactive Scaffold in Medicinal Chemistry

by Gayathri Rajendran, Deepu Bhanu, Baladhandapani Aruchamy, Prasanna Ramani, Nanjan Pandurangan, Kondapa Naidu Bobba, Eun Jung Oh, Ho Yun Chung, Prakash Gangadaran and Byeong-Cheol Ahn

Pharmaceuticals 2022, 15(10), 1250; https://doi.org/10.3390/ph15101250 - 11 Oct 2022

Cited by 31 | Viewed by 4474

Abstract

Chalcones are a class of privileged scaffolds with high medicinal significance due to the presence of an α,β-unsaturated ketone functionality. Numerous functional modifications of chalcones have been reported, along with their pharmacological behavior. The present review aims to summarize the structures from natural sources, synthesis methods, biological characteristics against infectious and non-infectious diseases, and uses of chalcones over the past decade, and their structure–activity relationship studies are detailed in depth. This critical review provides guidelines for the future design and synthesis of various chalcones. In addition, this could be highly supportive for medicinal chemists to develop more promising candidates for various infectious and non-infectious diseases. Full article

(This article belongs to the Special Issue Feature Reviews in Medicinal Chemistry)

► Show Figures

Figure 1

20 pages, 3687 KiB

Open AccessReview

A Review of the Biological Activity of Amidrazone Derivatives

by Renata Paprocka, Małgorzata Wiese-Szadkowska, Tomasz Kosmalski, Daria Frisch, Magdalena Ratajczak, Bożena Modzelewska-Banachiewicz and Renata Studzińska

Pharmaceuticals 2022, 15(10), 1219; https://doi.org/10.3390/ph15101219 - 30 Sep 2022

Cited by 3 | Viewed by 1815

Abstract

Amidrazones are widely used in chemical synthesis, industry and agriculture. We compiled some of the most important findings on the biological activities of amidrazones described in the years 2010–2022. The data were obtained using the ScienceDirect, Reaxys and Google Scholar search engines with keywords (amidrazone, carbohydrazonamide, carboximidohydrazide, aminoguanidine) and structure strategies. Compounds with significant biological activities were included in the review. The described structures derived from amidrazones include: amidrazone derivatives; aminoguanidine derivatives; complexes obtained using amidrazones as ligands; and some cyclic compounds obtained from amidrazones and/or containing an amidrazone moiety in their structures. This review includes chapters based on compound activities, including: tuberculostatic, antibacterial, antifungal, antiparasitic, antiviral, anti-inflammatory, cytoprotective, and antitumor compounds, as well as furin and acetylocholinesterase inhibitors. Detailed information on the compounds tested in vivo, along the mechanisms of action and toxicity of the selected amidrazone derivatives, are described. We describe examples of compounds that have a chance of becoming drugs due to promising preclinical or clinical research, as well as old drugs with new therapeutic targets (repositioning) which have the potential to be used in the treatment of other diseases. The described examples prove that amidrazone derivatives are a potential source of new therapeutic substances and deserve further research. Full article

(This article belongs to the Special Issue Feature Reviews in Medicinal Chemistry)

► Show Figures

Graphical abstract

Journal Menu

Journal Browser

Feature Reviews in Medicinal Chemistry

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Published Papers (11 papers)

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI