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Recent Advances in the Discovery and Development of Drugs for...
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Recent Advances in the Discovery and Development of Drugs for Civilization Diseases, 2nd Edition

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

Deadline for manuscript submissions: 25 November 2025 | Viewed by 1810

Special Issue Editors

Dr. Marcin Gackowski

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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
Special Issues, Collections and Topics in MDPI journals
Dr. Karolina Szewczyk-Golec

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Department of Medical Biology and Biochemistry, Collegium Medicum, Nicolaus Copernicus University, 85092 Bydgoszcz, Poland
Interests: biochemistry; metabolic diseases; melatonin; adipokines; inflammation; antioxidants; oxidative stress; cancer; parasites; skin ion transport
Special Issues, Collections and Topics in MDPI journals
Dr. Renata Studzińska

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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: drug development; anticancer drugs; anticancer treatment
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In the 21st century, the century in which all dreams come true, medicine allows 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 have 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 at an increasingly fast pace and under rising stress, we eat incorrectly because we eat on the go, we do not have time to prepare wholesome meals, and we do not have proper eating habits. We do not participate in 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. It is for this reason that it is so important to counteract these diseases. 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 on 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

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Related Special Issue

Published Papers (3 papers)

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Research

18 pages, 1599 KiB  
Article
SGLT2 Inhibitors in MASLD (Metabolic Dysfunction-Associated Steatotic Liver Disease) Associated with Sustained Hepatic Benefits, Besides the Cardiometabolic
by Mohamad Suki, Ashraf Imam, Johnny Amer, Yael Milgrom, Muhammad Massarwa, Wadi Hazou, Yariv Tiram, Ofer Perzon, Yousra Sharif, Joseph Sackran, Revital Alon, Nachum Lourie, Anat Hershko Klement, Safa Shibli, Tamer Safadi, Itamar Raz, Abed Khalaileh and Rifaat Safadi
Pharmaceuticals 2025, 18(8), 1118; https://doi.org/10.3390/ph18081118 - 26 Jul 2025
Viewed by 688
Abstract
Background and Aims: Sodium-glucose cotransporter-2 (SGLT2) inhibitors have shown promise in metabolic dysfunction-associated steatotic liver disease (MASLD). This large real-world study aimed to evaluate the effects of SGLT2 inhibitors on MASLD patients’ clinical outcomes and liver-related complications over extended follow-up. Patients and [...] Read more.
Background and Aims: Sodium-glucose cotransporter-2 (SGLT2) inhibitors have shown promise in metabolic dysfunction-associated steatotic liver disease (MASLD). This large real-world study aimed to evaluate the effects of SGLT2 inhibitors on MASLD patients’ clinical outcomes and liver-related complications over extended follow-up. Patients and Method: Data were sourced from TriNetX, a global health research platform with de-identified electronic medical records spanning 135 million patients across 112 healthcare organizations worldwide. We included MASLD adults diagnosed according to ICD9/10 criteria. Following propensity score matching based on 34 variables (demographics, comorbidities, laboratory tests and medication history), SGLT2 inhibitor-treated (n = 19,922) patients were compared with non-SGLT2 inhibitor (n = 19,922) cases. Exclusion criteria included baseline improved alanine aminotransferase (ALT) and alkaline phosphatase (ALP) levels > 4 upper normal limit (UNL), baseline advanced liver disease, liver transplant and cancer, past anticoagulation and non-MASLD etiologies. Assessed outcomes included survival, biochemical, hematologic, AFP, metabolic and cardiovascular parameters, progression to advanced liver disease (ALD), synthetic function, and metabolic markers over 1, 5, and 10 years. Results: Following matching, both cohorts were well-balanced across baseline characteristics. After one year, the SGLT2 inhibitor group demonstrated significantly reduced BMI (33.2 ± 6.2 vs. 34.1 ± 6.5 kg/m2, p < 0.001), improved ALT (40.3 ± 31.5 vs. 48.3 ± 41.2 U/L, p < 0.001), and better glycemic control (HbA1c 7.35 ± 1.51% vs. 7.93 ± 1.72%, p < 0.001). The SGLT2 inhibitor group showed higher 10-year survival rates (95.00% vs. 88.69%, p < 0.001), fewer cardiovascular events (10.19% vs. 11.80%, p < 0.001), and markedly reduced progression to advanced liver disease (6.90% vs. 14.15%, p < 0.001). These benefits were consistent across clinical, laboratory, and medication-defined ALD categories. Notably, rates of hepatic decompensation events were significantly lower with SGLT2 inhibitor therapy. Conclusions: In this large real-world cohort, SGLT2 inhibitor use in MASLD patients was associated with significantly improved long-term survival, cardiovascular, and liver-related outcomes over 10 years of follow-up. These benefits likely result from combined metabolic improvements, anti-inflammatory effects, and direct hepatoprotective mechanisms. SGLT2 inhibitors represent a promising therapeutic strategy for improving outcomes in MASLD. Full article
(This article belongs to the Special Issue Recent Advances in the Discovery and Development of Drugs for Civilization Diseases, 2nd Edition)
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19 pages, 827 KiB  
Article
New Derivatives of Caracasine Acid with Anti-Leukemic Activity and Limited Effectiveness in Spheroid Cultures
by Alírica Isabel Suárez, Katiuska Chávez, Jenny Valentina Garmendia, Claudia Valentina De Sanctis, Soňa Gurská, Petr Džubák, Marian Hajduch and Juan Bautista De Sanctis
Pharmaceuticals 2025, 18(7), 1043; https://doi.org/10.3390/ph18071043 - 15 Jul 2025
Viewed by 387
Abstract
Background: The natural compounds caracasine acid (1) and its methyl ester, caracasine (2), isolated from the flowers of Croton micans, are effective against several tumor cell lines. Five semi-synthetic derivatives (3–7) were synthesized based [...] Read more.
Background: The natural compounds caracasine acid (1) and its methyl ester, caracasine (2), isolated from the flowers of Croton micans, are effective against several tumor cell lines. Five semi-synthetic derivatives (3–7) were synthesized based on these structures. The study aimed to evaluate the cytotoxic activity of these compounds in 2D and spheroid cultures. Methods: The assays were performed in a panel of 12 human cell lines, 8 cancer and 4 normal cell lines. The compounds were evaluated on spheroids derived from the HCT116, HCT116 p53 knockout (p53KO), A549, and U2OS cell lines, as well as mixed spheroids comprising tumor cells and normal fibroblasts. Results: The parent compound (1), the natural ester (2), and two novel derivatives, the anhydride (7) and the cyclohexanol ester (3), demonstrated cytotoxicity against different leukemic cells and HCT116, HCT116 p53 knockout (p53KO), A549, and U2OS cell lines in conventional two-dimensional cultures. Peroxide formation, however, was significantly higher in leukemic cell lines (p < 0.01) in 2D culture as compared with the other tumor cell lines. The compounds did not induce cell death in spheroid cultures; caspases 8, 9, and 3 were not activated upon treatment. Conclusions: These findings indicate potential applications in leukemia treatment, albeit with limited efficacy against solid tumors. Full article
(This article belongs to the Special Issue Recent Advances in the Discovery and Development of Drugs for Civilization Diseases, 2nd Edition)
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13 pages, 677 KiB  
Article
Analysis of Scyllo-Inositol in a Wistar Rat Animal Model—A Preliminary Study
by Karol Wiśniewski, Kamila Zglejc-Waszak, Tomasz Antonowski, Joanna Szablinska-Piernik, Jerzy Juskiewicz, Lesław Lahuta, Marcin Jozwik and Joanna Wojtkiewicz
Pharmaceuticals 2025, 18(7), 954; https://doi.org/10.3390/ph18070954 - 25 Jun 2025
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Abstract
Background: Scyllo-inositol (SCI) is a naturally occurring carbocyclic sugar implicated in many biological processes. Studies have highlighted the potential of using SCI in Alzheimer’s therapy. However, in order to fully use this compound in the treatment of neurovegetative diseases, its pharmacokinetics must [...] Read more.
Background: Scyllo-inositol (SCI) is a naturally occurring carbocyclic sugar implicated in many biological processes. Studies have highlighted the potential of using SCI in Alzheimer’s therapy. However, in order to fully use this compound in the treatment of neurovegetative diseases, its pharmacokinetics must be thoroughly understood. Objectives: We undertook the task of analyzing SCI in a Wistar rat animal model. The aim of this study was to observe the changes in SCI concentration after oral administration. Methods: All rats received 10 mg/kg of SCI as a solution in distilled water by oral gavage. Estimated parameters were based on the serum concentration of SCI observed in six individual rats with regard to time. Results: The first peak concentration appeared at 30 min for SCI. Thereafter, the serum SCI concentration increased rapidly and reached its highest level after approximately 1.5 h. There was no second peak in SCI concentration. The elimination half-life was determined to be 10.07 h and the mean residence time was 14.52 h. There were no side effects of SCI supplementation noticed during the study. Conclusions: Although our results present an analysis of SCI immediately after oral administration up to 48 h, further studies are necessary. Full article
(This article belongs to the Special Issue Recent Advances in the Discovery and Development of Drugs for Civilization Diseases, 2nd Edition)
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