Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
4.7
4.6
Journals
Pharmaceuticals
Special Issues
Recent Advances in the Discovery and Development of Drugs for...
share announcement

Recent Advances in the Discovery and Development of Drugs for Civilization Diseases

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

Deadline for manuscript submissions: 1 September 2024 | Viewed by 6314

Special Issue Editors

Dr. Marcin Gackowski

E-Mail
Guest Editor
Department of Toxicology and Bromatology, Faculty of Pharmacy, L. Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, A. Jurasza 2 Street, 85089 Bydgoszcz, Poland
Interests: molecular modeling; oxidative stress; geriatric patients; drug design; QSAR
Dr. Karolina Szewczyk-Golec

E-Mail Website
Guest Editor
Department of Medical Biology and Biochemistry, Collegium Medicum, Nicolaus Copernicus University, 85-092 Bydgoszcz, Poland
Interests: biochemistry; cancer; metabolic diseases; obesity; oxidative stress
Special Issues, Collections and Topics in MDPI journals
Dr. Renata Studzińska

E-Mail Website
Guest Editor
Department of Organic Chemistry, Faculty of Pharmacy, L. Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, A. Jurasza 2 Street, 85089 Bydgoszcz, Poland
Interests: metabolic diseases; organic synthesis; antitumor activity; civilization diseases; bioactive compounds

Special Issue Information

Dear Colleagues,

In the 21st century, the century that makes all dreams come true, medicine will allow us to forget about pain, old age, and diseases. Nothing could be more wrong. Civilization diseases, otherwise known as lifestyle diseases, social diseases, or diseases of the 21st century include non-communicable diseases that spread around the world due to the development of civilization. This phenomenon is accompanied by industrialization, economic development, and, unfortunately, also environmental pollution. We live faster and faster and under more and more stress, we eat incorrectly because we eat on the run, we do not have time to prepare wholesome meals, and we do not have proper eating habits. We do not have enough physical exercise and we smoke cigarettes and abuse alcohol. It turns out that lifestyle diseases are responsible for over 80% of all deaths worldwide. They are responsible for not only shortening the length of life but also the deterioration of its quality. That is why it is so important to counteract them. In order to be able to fight civilization diseases more effectively, proper prevention is needed, with new treatments and drugs. In this Special Issue, we invite potential authors to submit manuscripts in the form of research articles, reviews, or communications that contribute to every aspect of medicinal chemistry, the discovery of new drugs for broadly understood civilization diseases, their synthesis, mechanisms of action, biological activity, and advances in drug dosage forms. This Special Issue will welcome original, high-quality scientific articles, reviews, and communications in the field of computational methods for drug design, i.e., in silico research, as well as synthetic and biochemical approaches in this topic.

Dr. Marcin Gackowski
Dr. Karolina Szewczyk-Golec
Dr. Renata Studzińska
Guest Editors

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

  • anticancer drugs
  • anticancer treatment
  • anticoagulants
  • atherosclerosis
  • cardiovascular disease
  • civilization diseases
  • diabetes mellitus
  • drug development
  • in silico research
  • medication form/drug dosage form
  • molecular descriptors
  • molecular docking
  • molecular dynamics
  • molecular modeling
  • neoplastic disease
  • obesity
  • QSAR
  • radiopharmaceuticals
  • synthesis of bioactive compounds
  • type 2 diabetes

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

42 pages, 16821 KiB  
Article
Butterfly Effect in Cytarabine: Combined NMR-NQR Experiment, Solid-State Computational Modeling, Quantitative Structure-Property Relationships and Molecular Docking Study
by Jolanta Natalia Latosińska, Magdalena Latosińska, Janez Seliger, Veselko Žagar and Tomaž Apih
Pharmaceuticals 2024, 17(4), 445; https://doi.org/10.3390/ph17040445 - 29 Mar 2024
Viewed by 949
Abstract
Cytarabine (Ara-C) is a synthetic isomer of cytidine that differs from cytidine and deoxycytidine only in the sugar. The use of arabinose instead of deoxyribose hinders the formation of phosphodiester linkages between pentoses, preventing the DNA chain from elongation and interrupting the DNA [...] Read more.
Cytarabine (Ara-C) is a synthetic isomer of cytidine that differs from cytidine and deoxycytidine only in the sugar. The use of arabinose instead of deoxyribose hinders the formation of phosphodiester linkages between pentoses, preventing the DNA chain from elongation and interrupting the DNA synthesis. The minor structural alteration (the inversion of hydroxyl at the 2′ positions of the sugar) leads to change of the biological activity from anti-depressant and DNA/RNA block builder to powerful anti-cancer. Our study aimed to determine the molecular nature of this phenomenon. Three 1H-14N NMR-NQR experimental techniques, followed by solid-state computational modelling (Quantum Theory of Atoms in Molecules, Reduced Density Gradient and 3D Hirshfeld surfaces), Quantitative Structure–Property Relationships, Spackman’s Hirshfeld surfaces and Molecular Docking were used. Multifaceted analysis—combining experiments, computational modeling and molecular docking—provides deep insight into three-dimensional packing at the atomic and molecular levels, but is challenging. A spectrum with nine lines indicating the existence of three chemically inequivalent nitrogen sites in the Ara-C molecule was recorded, and the lines were assigned to them. The influence of the structural alteration on the NQR parameters was modeled in the solid (GGA/RPBE). For the comprehensive description of the nature of these interactions several factors were considered, including relative reactivity and the involvement of heavy atoms in various non-covalent interactions. The binding modes in the solid state and complex with dCK were investigated using the novel approaches: radial plots, heatmaps and root-mean-square deviation of the binding mode. We identified the intramolecular OH···O hydrogen bond as the key factor responsible for forcing the glycone conformation and strengthening NH···O bonds with Gln97, Asp133 and Ara128, and stacking with Phe137. The titular butterfly effect is associated with both the inversion and the presence of this intramolecular hydrogen bond. Our study elucidates the differences in the binding modes of Ara-C and cytidine, which should guide the design of more potent anti-cancer and anti-viral analogues. Full article
(This article belongs to the Special Issue Recent Advances in the Discovery and Development of Drugs for Civilization Diseases)
►▼ Show Figures

Graphical abstract

17 pages, 7284 KiB  
Article
Novel Thiourea and Oxime Ether Isosteviol-Based Anticoagulants: MD Simulation and ADMET Prediction
by Marcin Gackowski, Mateusz Jędrzejewski, Sri Satya Medicharla, Rajesh Kondabala, Burhanuddin Madriwala, Katarzyna Mądra-Gackowska and Renata Studzińska
Pharmaceuticals 2024, 17(2), 163; https://doi.org/10.3390/ph17020163 - 28 Jan 2024
Viewed by 894
Abstract
Activated blood coagulation factor X (FXa) plays a critical initiation step of the blood-coagulation pathway and is considered a desirable target for anticoagulant drug development. It is reversibly inhibited by nonvitamin K antagonist oral anticoagulants (NOACs) such as apixaban, betrixaban, edoxaban, and rivaroxaban. [...] Read more.
Activated blood coagulation factor X (FXa) plays a critical initiation step of the blood-coagulation pathway and is considered a desirable target for anticoagulant drug development. It is reversibly inhibited by nonvitamin K antagonist oral anticoagulants (NOACs) such as apixaban, betrixaban, edoxaban, and rivaroxaban. Thrombosis is extremely common and is one of the leading causes of death in developed countries. In previous studies, novel thiourea and oxime ether isosteviol derivatives as FXa inhibitors were designed through a combination of QSAR studies and molecular docking. In the present contribution, molecular dynamics (MD) simulations were performed for 100 ns to assess binding structures previously predicted by docking and furnish additional information. Moreover, three thiourea- and six oxime ether-designed isosteviol analogs were then examined for their drug-like and ADMET properties. MD simulations demonstrated that four out of the nine investigated isosteviol derivatives, i.e., one thiourea and three oxime ether ISV analogs, form stable complexes with FXa. These derivatives interact with FXa in a manner similar to Food and Drug Administration (FDA)-approved drugs like edoxaban and betrixaban, indicating their potential to inhibit factor Xa activity. One of these derivatives, E24, displays favorable pharmacokinetic properties, positioning it as the most promising drug candidate. This, along with the other three derivatives, can undergo further chemical synthesis and bioassessment. Full article
(This article belongs to the Special Issue Recent Advances in the Discovery and Development of Drugs for Civilization Diseases)
►▼ Show Figures

Figure 1

17 pages, 4377 KiB  
Article
The Tandem of Liquid Chromatography and Network Pharmacology for the Chemical Profiling of Pule’an Tablets and the Prediction of Mechanism of Action in Treating Prostatitis
by Hui Zhuge, Zhiwei Ge, Jiaojiao Wang, Jianbiao Yao, Jiayu He, Yi Wang, Yingchao Wang and Yu Tang
Pharmaceuticals 2024, 17(1), 56; https://doi.org/10.3390/ph17010056 - 28 Dec 2023
Cited by 1 | Viewed by 1170
Abstract
Prostatitis, a prevalent urinary tract disorder in males, has a complex etiology that leads to severe clinical discomfort. Pule’an Tablets, a classic single-component formulation primarily based on rapeseed pollen, have been clinically proven to have a beneficial therapeutic effect on both prostatitis and [...] Read more.
Prostatitis, a prevalent urinary tract disorder in males, has a complex etiology that leads to severe clinical discomfort. Pule’an Tablets, a classic single-component formulation primarily based on rapeseed pollen, have been clinically proven to have a beneficial therapeutic effect on both prostatitis and benign prostatic hyperplasia. However, there is currently a lack of research on the chemical composition and mechanisms of action of Pule’an Tablets in treating prostatitis. In this study, using liquid chromatography–mass spectrometry (LC-MS), a total of 53 compounds in Pule’an Tablets were identified, including flavonoids, phenylpropionamides, lipids, glucosinolates, and nucleic acids. Subsequently, through a network pharmacology analysis, potential target genes and their mechanisms of action were predicted accordingly. The results suggested that genes such as LPAR5, LPAR6, LPAR4, LPAR3, LPAR2, LPAR1, F2, ENPP2, MMP9, and TNF, along with pathways like prostate cancer, endocrine resistance, bladder cancer, and the IL-17 signaling pathway, may represent potential pathways involved in the therapeutic effects of Pule’an Tablets. This study represents the first systematic investigation into the chemical composition of Pule’an Tablets, shedding light on the potential mechanisms underlying their efficacy in treating prostatitis. These findings could serve as a valuable reference for future pharmacological research on Pule’an Tablets. Full article
(This article belongs to the Special Issue Recent Advances in the Discovery and Development of Drugs for Civilization Diseases)
►▼ Show Figures

Graphical abstract

14 pages, 4167 KiB  
Article
Compensative Resistance to Erastin-Induced Ferroptosis in GPX4 Knock-Out Mutants in HCT116 Cell Lines
by Malgorzata Adamiec-Organisciok, Magdalena Wegrzyn, Lukasz Cienciala, Damian Sojka, Joanna Nackiewicz and Magdalena Skonieczna
Pharmaceuticals 2023, 16(12), 1710; https://doi.org/10.3390/ph16121710 - 10 Dec 2023
Viewed by 1341
Abstract
Ferroptosis results from the accumulation of oxidized and damaged lipids which then leads to programmed cell death. This programmed process is iron-dependent, and as a fundamental biological process, plays a crucial role in tissue homeostasis. The ferroptosis molecular pathway depends on self-regulatory genes: [...] Read more.
Ferroptosis results from the accumulation of oxidized and damaged lipids which then leads to programmed cell death. This programmed process is iron-dependent, and as a fundamental biological process, plays a crucial role in tissue homeostasis. The ferroptosis molecular pathway depends on self-regulatory genes: GPX4; TFRC; ACSL4; FSP1; SLC7A11, and PROM2. Some of them were considered here as ferro-sensitive or ferro-resistance markers. We examined the impact of GPX4 gene knock-out, using the CRISPR/Cas-9 technique, on ferroptosis induction in the HCT116 colorectal cancer cell line. The results confirmed that cells lacking the GPX4 gene (GPX4 KO) should be more susceptible to ferroptosis after erastin treatment. However, the decrease in cell viability was not as significant as we initially assumed. Based on the lipid peroxidation markers profile and RT-qPCR gene expression analysis, we revealed the activation of an alternative antioxidant system supporting GPX4 KO cells, mostly for cellular ferroptotic death avoidance. Increased expression of FSP1 and PRDX1 genes in knock-out mutants was associated with their function—recognized here as ferroptosis suppressors. For such reasons, studies on the role of GPX4 and other crucial genes from the ferroptotic pathway should be explored. Despite promising prospects, the utilization of ferroptosis mechanisms in cancer therapy remains at the stage of experimental and in vitro preclinical studies. Full article
(This article belongs to the Special Issue Recent Advances in the Discovery and Development of Drugs for Civilization Diseases)
►▼ Show Figures

Graphical abstract

24 pages, 8851 KiB  
Article
Searching for Natural Aurora a Kinase Inhibitors from Peppers Using Molecular Docking and Molecular Dynamics
by Paweł Siudem, Łukasz Szeleszczuk and Katarzyna Paradowska
Pharmaceuticals 2023, 16(11), 1539; https://doi.org/10.3390/ph16111539 - 31 Oct 2023
Cited by 1 | Viewed by 921
Abstract
Natural products are the precursors of many medicinal substances. Peppers (Piper, Capsicum, Pimienta) are a rich source of compounds with potential multidirectional biological activity. One of the studied directions is antitumor activity. Little research has been carried out so far [...] Read more.
Natural products are the precursors of many medicinal substances. Peppers (Piper, Capsicum, Pimienta) are a rich source of compounds with potential multidirectional biological activity. One of the studied directions is antitumor activity. Little research has been carried out so far on the ability of the compounds contained in peppers to inhibit the activity of Aurora A kinase, the overexpression of which is characteristic of cancer development. In this study, molecular docking methods, as well as molecular dynamics, were used, looking for compounds that could inhibit the activity of Aurora A kinase and trying to determine whether there is a relationship between the stimulation of the TRPV1 receptor and the inhibition of Aurora A kinase. We compared our results with anticancer activity studied earlier on MCF-7 cell lines (breast cancer cells). Our research indicates that the compounds contained in peppers can inhibit Aurora A. Further in vitro research is planned to confirm the obtained results. Full article
(This article belongs to the Special Issue Recent Advances in the Discovery and Development of Drugs for Civilization Diseases)
►▼ 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