New Approaches for the Treatment of Civilization Diseases

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Medicine".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 12398

Special Issue Editor


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Guest Editor
Independent Radiopharmacy Unit, Department of Organic Chemistry, Faculty of Pharmacy, Medical University of Lublin, PL-20093 Lublin, Poland
Interests: synthesis; antimicrobial activity; anticancer activity; heterocyklic compound; SAR

Special Issue Information

Dear Colleagues,

Civilization diseases are called the epidemy of the 21st century. They spread globally, are non-contagious, yet lead to disability and result in over 80% of premature deaths. Living in a hurry, full of stressful stimuli, poor nutrition, as well as climate change and using stimulants are the causes that often lead to a shortening of life expectancy or significantly reduce its quality. The most often diseases of civilization include disorders of the cardiovascular system, obesity, atherosclerosis, diabetes, cancer, allergies and osteoporosis as well as disorders of the central systemsuch as mental (eg. schizophrenia) and neurodegenerative diseases (Parkinson’s and Alzheimer’s disease). The number of patients with depression, neurosis and schizophrenia is increasing. Despite the continuous progress of medical science and the introduction of new drugs to the market, the effectiveness of treatment of many diseases remains unsatisfactory. One of the major problems with pharmacotherapy is the large variability in patients' response to the drug. Therefore, it is necessary to individualize the treatment and to optimize the substances of the pharmacotherapy used. In this special issue, we invite potential authors to submit manuscripts regarding the discovery of anti-cancer, anti-diabetes, anti-tuberculosis and drugs for mental and neurodegenerative diseases. Publications covering, inter alia, the synthesis, mechanism of action and biological activity of the compounds are welcome. Both original and review article contributions will be welcome.

Dr. Monika Pitucha
Guest Editor

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Published Papers (3 papers)

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Research

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19 pages, 3310 KiB  
Article
Potential Anticancer Agents against Melanoma Cells Based on an As-Synthesized Thiosemicarbazide Derivative
by Paweł Kozyra, Agnieszka Korga-Plewko, Zbigniew Karczmarzyk, Anna Hawrył, Waldemar Wysocki, Michał Człapski, Magdalena Iwan, Marta Ostrowska-Leśko, Emilia Fornal and Monika Pitucha
Biomolecules 2022, 12(2), 151; https://doi.org/10.3390/biom12020151 - 18 Jan 2022
Cited by 20 | Viewed by 3067
Abstract
In this paper, thiosemicarbazide derivatives were synthesized as potential anticancer agents. X-ray investigations for 1-(2,4-dichlorophenoxy)acetyl-4-(2-fluorophenyl) thiosemicarbazide, 1-(2,4-dichlorophenoxy)acetyl-4-(4-metylothiophenyl)thiosemicarbazide and 1-(2,4-di chlorophenoxy)acetyl-4-(4-iodophenyl)thiosemicarbazide were carried out in order to confirm the synthesis pathways, identify their tautomeric forms, analyze the conformational preferences of molecules, and identify intra- [...] Read more.
In this paper, thiosemicarbazide derivatives were synthesized as potential anticancer agents. X-ray investigations for 1-(2,4-dichlorophenoxy)acetyl-4-(2-fluorophenyl) thiosemicarbazide, 1-(2,4-dichlorophenoxy)acetyl-4-(4-metylothiophenyl)thiosemicarbazide and 1-(2,4-di chlorophenoxy)acetyl-4-(4-iodophenyl)thiosemicarbazide were carried out in order to confirm the synthesis pathways, identify their tautomeric forms, analyze the conformational preferences of molecules, and identify intra- and intermolecular interactions in the crystalline state. TLC and RP-HPLC analyses were used to determine lipophilicity. The lipophilicity analysis revealed that the 4-substituted halogen derivatives of thiosemicarbazides showed greater lipophilicity compared with 2-substituted derivatives. The optimal range of lipophilicity for biologically active compounds logkw is between 4.14 and 4.78. However, as the analysis showed, it is not a decisive parameter. The cytotoxicity of the new compounds was evaluated against both the G-361 and BJ cell lines. Cytotoxicity analyses and cell-cycle and cell apoptosis assays were performed. The MTT test demonstrated that three compounds were cytotoxic to melanoma cells and not toxic to normal fibroblasts in the concentration range used. The cell cycle analysis showed that the compounds had no significant effect on the cell cycle inhibition. An extensive gene expression analysis additionally revealed that all compounds tested downregulated the expression of dihydroorotate dehydrogenase (DHODH). DHODH is a mitochondrial enzyme involved in the de novo synthesis of pyrimidines. Due to the rapid rate of cancer cell proliferation and the increased demand for nucleotide synthesis, it has become a potential therapeutic target. Full article
(This article belongs to the Special Issue New Approaches for the Treatment of Civilization Diseases)
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17 pages, 13687 KiB  
Article
Vascular Tissue Specific miRNA Profiles Reveal Novel Correlations with Risk Factors in Coronary Artery Disease
by Katrīna D. Neiburga, Baiba Vilne, Sabine Bauer, Dario Bongiovanni, Tilman Ziegler, Mark Lachmann, Simon Wengert, Johann S. Hawe, Ulrich Güldener, Annie M. Westerlund, Ling Li, Shichao Pang, Chuhua Yang, Kathrin Saar, Norbert Huebner, Lars Maegdefessel, DigiMed Bayern Consortium, Rüdiger Lange, Markus Krane, Heribert Schunkert and Moritz von Scheidtadd Show full author list remove Hide full author list
Biomolecules 2021, 11(11), 1683; https://doi.org/10.3390/biom11111683 - 12 Nov 2021
Cited by 15 | Viewed by 3594
Abstract
Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. Non-coding RNAs have already been linked to CVD development and progression. While microRNAs (miRs) have been well studied in blood samples, there is little data on tissue-specific miRs in cardiovascular relevant [...] Read more.
Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. Non-coding RNAs have already been linked to CVD development and progression. While microRNAs (miRs) have been well studied in blood samples, there is little data on tissue-specific miRs in cardiovascular relevant tissues and their relation to cardiovascular risk factors. Tissue-specific miRs derived from Arteria mammaria interna (IMA) from 192 coronary artery disease (CAD) patients undergoing coronary artery bypass grafting (CABG) were analyzed. The aims of the study were 1) to establish a reference atlas which can be utilized for identification of novel diagnostic biomarkers and potential therapeutic targets, and 2) to relate these miRs to cardiovascular risk factors. Overall, 393 individual miRs showed sufficient expression levels and passed quality control for further analysis. We identified 17 miRs–miR-10b-3p, miR-10-5p, miR-17-3p, miR-21-5p, miR-151a-5p, miR-181a-5p, miR-185-5p, miR-194-5p, miR-199a-3p, miR-199b-3p, miR-212-3p, miR-363-3p, miR-548d-5p, miR-744-5p, miR-3117-3p, miR-5683 and miR-5701–significantly correlated with cardiovascular risk factors (correlation coefficient >0.2 in both directions, p-value (p < 0.006, false discovery rate (FDR) <0.05). Of particular interest, miR-5701 was positively correlated with hypertension, hypercholesterolemia, and diabetes. In addition, we found that miR-629-5p and miR-98-5p were significantly correlated with acute myocardial infarction. We provide a first atlas of miR profiles in IMA samples from CAD patients. In perspective, these miRs might play an important role in improved risk assessment, mechanistic disease understanding and local therapy of CAD. Full article
(This article belongs to the Special Issue New Approaches for the Treatment of Civilization Diseases)
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Review

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16 pages, 1166 KiB  
Review
Current Approaches and Tools Used in Drug Development against Parkinson’s Disease
by Oliwia Koszła, Piotr Stępnicki, Agata Zięba, Angelika Grudzińska, Dariusz Matosiuk and Agnieszka A. Kaczor
Biomolecules 2021, 11(6), 897; https://doi.org/10.3390/biom11060897 - 16 Jun 2021
Cited by 10 | Viewed by 4013
Abstract
Parkinson’s disease is a progressive neurodegenerative disorder characterized by the death of nerve cells in the substantia nigra of the brain. The treatment options for this disease are very limited as currently the treatment is mainly symptomatic, and the available drugs are not [...] Read more.
Parkinson’s disease is a progressive neurodegenerative disorder characterized by the death of nerve cells in the substantia nigra of the brain. The treatment options for this disease are very limited as currently the treatment is mainly symptomatic, and the available drugs are not able to completely stop the progression of the disease but only to slow it down. There is still a need to search for new compounds with the most optimal pharmacological profile that would stop the rapidly progressing disease. An increasing understanding of Parkinson’s pathogenesis and the discovery of new molecular targets pave the way to develop new therapeutic agents. The use and selection of appropriate cell and animal models that better reflect pathogenic changes in the brain is a key aspect of the research. In addition, computer-assisted drug design methods are a promising approach to developing effective compounds with potential therapeutic effects. In light of the above, in this review, we present current approaches for developing new drugs for Parkinson’s disease. Full article
(This article belongs to the Special Issue New Approaches for the Treatment of Civilization Diseases)
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