4.7 Editorial Material

Novel Strategies in the Development of New Therapies, Drug Substances, and Drug Carriers Volume I

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Article Biochemistry & Molecular Biology

Vitamin D Analogs Regulate the Vitamin D System and Cell Viability in Ovarian Cancer Cells

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Summary: This study found that newly developed low calcemic vitamin D analogs (an1,25Ds) can be used as anticancer agents in ovarian cancer cells, with PRI-5202 showing the best efficacy. The potency of these analogs and their ability to increase CYP24A1 expression in HGSOC cell lines were dependent on the cell line and chemical structure, suggesting that further optimization of the analogs' structure may lead to new treatment options for ovarian cancer.

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Gold (III) Derivatives in Colon Cancer Treatment

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Summary: Cancer is a major cause of illness and death worldwide. Colorectal cancer is the third most common cancer in men and the second most common in women. Standard antitumor therapies, such as cisplatin, have limitations due to their lack of specificity for tumor cells, drug resistance development, and severe side effects. Therefore, new methods and strategies for treating colorectal cancer are urgently needed. Current research focuses on novel platinum and other metal-based drugs, such as gold, silver, iridium, or ruthenium. Au(III) compounds are considered promising candidates for colorectal cancer treatment due to their structural similarity to Pt(II). However, their stability under physiological conditions needs improvement by combining with various ligands. This review summarizes the progress in developing stable Au(III) complexes with potential cytotoxic activity against cancer cells. Additionally, it highlights that the anticancer effects of Au derivatives are mediated by protein structures, such as thioredoxin reductase, rather than nucleic acids. The current state of in vivo studies is also discussed.

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The Cytotoxic Effect of Copper (II) Complexes with Halogenated 1,3-Disubstituted Arylthioureas on Cancer and Bacterial Cells

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Combined Protein and Alkaloid Research of Chelidonium majus Latex Reveals CmMLP1 Accompanied by Alkaloids with Cytotoxic Potential to Human Cervical Carcinoma Cells

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Summary: The study on the interaction between latex protein and alkaloids in Chelidonium majus L. revealed their ability to reduce the viability of cervical cancer cells. This novel approach provides insights into plant defense mechanisms and can contribute to pharmacological research.

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Functional Studies of Plant Latex as a Rich Source of Bioactive Compounds: Focus on Proteins and Alkaloids

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Summary: Latex, produced by specialized cells, plays a crucial role in plants' defense system against herbivory and pathogens, containing a variety of active compounds beneficial for both plants and human health. Despite the long-standing tradition of using latex in medicine, there are still many promising molecules waiting to be explored.

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Development of In Vitro and In Vivo Evaluation Systems for Vitamin D Derivatives and Their Application to Drug Discovery

Kaori Yasuda et al.

Summary: The developed in vitro system assesses vitamin D derivatives' affinity for VDR and resistance to CYP24A1-mediated metabolism. In vivo models with gene deficiencies can evaluate therapeutic effects and activities of vitamin D derivatives.

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New N-Substituted-1,2,4-triazole Derivatives of Pyrrolo[3,4-d]pyridazinone with Significant Anti-Inflammatory Activity-Design, Synthesis and Complementary In Vitro, Computational and Spectroscopic Studies

Lukasz Szczukowski et al.

Summary: This study synthesized novel N-substituted-1,2,4-triazole-based derivatives of pyrrolo[3,4-d]pyridazinone, some of which showed significant COX-2 inhibitory activity and selectivity, while also helping reduce oxidative stress-induced cell damage in vitro experiments.

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New Approaches to Assess Mechanisms of Action of Selective Vitamin D Analogues

John Wesley Pike et al.

Summary: Recent studies have identified key principles governing vitamin D transcription, including the rapid binding of the VDR-ligand complex to enhancer elements at open chromatin sites. This initial action triggers downstream molecular events, such as histone acetylation and recruitment of additional modifiers, leading to gene expression. These sequential events provide insights into the activation of genes both in vitro and in vivo, suggesting potential applications for studying vitamin D analogs and synthetic compounds.

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Synthesis, Molecular Docking and Antiplasmodial Activities of New Tetrahydro-β-Carbolines

Anna Jaromin et al.

Summary: Malaria remains a major threat with drug resistance on the rise. New tetrahydro-beta-carbolines were synthesized and tested for antiplasmodial activity, with N-(3,3-dimethylbutyl)-1-octyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b] indole-3-carboxamide (7) showing the most promising results. Further research is being conducted on its potential mechanisms of action and delivery systems.

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Antitumor Activity and Mechanism of Action of Hormonotoxin, an LHRH Analog Conjugated to Dermaseptin-B2, a Multifunctional Antimicrobial Peptide

Mickael Couty et al.

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Synthesis of Novel Pyrido[1,2-c]pyrimidine Derivatives with 6-Fluoro-3-(4-piperidynyl)-1,2-benzisoxazole Moiety as Potential SSRI and 5-HT1A Receptor Ligands

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Summary: Novel compounds with high affinities for 5-HT1A receptor were synthesized and characterized through a series of experiments, showing potential for therapeutic applications.

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In Vitro and In Vivo Efficacy of a Novel Glucose-Methotrexate Conjugate in Targeted Cancer Treatment

Marta Wozniak et al.

Summary: GLU-MTX, a novel glucose-methotrexate conjugate, demonstrates considerable tumor selectivity and significant growth inhibition in a range of tumor cells, both in vitro and in vivo experiments. The inhibitor of GLUT1, 4,6-O-ethylidene-alpha-D-glucose (EDG), interferes with the effects of GLU-MTX, validating the glucose-mediated drug uptake selectivity.

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Differential Response of Lung Cancer Cells, with Various Driver Mutations, to Plant Polyphenol Resveratrol and Vitamin D Active Metabolite PRI-2191

Ewa Maj et al.

Summary: Plant polyphenols and vitamin D active metabolite show distinct biological effects on lung cancer cells with different genetic backgrounds, with responses varying based on the genetic profile of the cells. These differences may be attributed to epigenetic modifications induced by divergent smoking histories associated with the cell subtypes.

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Article Biochemistry & Molecular Biology

Poly(chitosan-ester-ether-urethane) Hydrogels as Highly Controlled Genistein Release Systems

Martyna Zagorska-Dziok et al.

Summary: Polymeric hydrogels play an increasingly important role in medicine, pharmacy, and cosmetology due to their favorable physicochemical properties and biocompatibility. This study synthesized new poly(chitosan-ester-ether-urethane) hydrogels and studied the kinetic release of genistein from these biomaterials. The developed hydrogels show non-toxicity to skin cells and a relatively highly controlled release profile of genistein.

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Article Biochemistry & Molecular Biology

In Vitro and In Silico Characterization of an Antimalarial Compound with Antitumor Activity Targeting Human DNA Topoisomerase IB

Bini Chhetri Soren et al.

Summary: A drug obtained from an open-access drug bank was found to strongly and irreversibly inhibit the cleavage step of human DNA topoisomerase IB, reducing cell viability in three different cancer cell lines. Molecular docking and dynamics simulations suggested that the drug binds inside the enzyme's catalytic site, potentially offering a lead compound for developing an efficient anti-tumor molecule targeting human DNA topoisomerase IB.

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Epigenetic Targeting of Histone Deacetylases in Diagnostics and Treatment of Depression

Hyun-Sun Park et al.

Summary: Depression is a prevalent and disabling illness that places substantial burdens on patients, families, healthcare systems, and the economy. Some patients are unresponsive to current therapies, highlighting the need for more effective, accessible, and tolerable treatments. Pharmacological regulation of histone acetylation status is being explored as a potential clinical strategy, with inhibitors of histone deacetylases showing promise as novel therapeutics.

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Article Biochemistry & Molecular Biology

Anti-Cancer and Electrochemical Properties of Thiogenistein-New Biologically Active Compound

Elzbieta U. Stolarczyk et al.

Summary: The study investigates the oxidative properties of a new thiolated genistein analog on a gold electrode, revealing one irreversible and one quasi-reversible oxidation reaction in PBS buffer. Further experiments show that the analog exhibits higher cytotoxic activity towards prostate cancer cells and is safer for normal prostate epithelial cells compared to genistein itself.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

Article Biochemistry & Molecular Biology

Stereo-Specific Modulation of the Extracellular Calcium-Sensing Receptor in Colon Cancer Cells

Martin Schepelmann et al.

Summary: The study demonstrated that pro-inflammatory effects in colon cancer cells are mediated through CaSR activation, and non-CaSR selective enantiomer will be a valuable tool for investigations in CaSR-mediated processes.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

Review Biochemistry & Molecular Biology

Design and Synthesis of Fluoro Analogues of Vitamin D

Fumihiro Kawagoe et al.

Summary: Discovery of the versatile functions of vitamin D-3 and its metabolites has driven the design and synthesis of numerous vitamin D-3 analogues with the addition of electronegative fluorine atoms to alter their properties. Many fluorinated vitamin D-3 analogues have been successfully designed and synthesized, with this review providing a summary of their molecular structures and synthetic methodologies.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

Review Biochemistry & Molecular Biology

5-HT Receptors and the Development of New Antidepressants

Grzegorz Slifirski et al.

Summary: Serotonin plays a crucial role in regulating emotions, memory, sleep, and thermal regulation in the human body. Modulating serotonin transmission is considered a key strategy in the search for new antidepressants, and combining different pharmacological activities towards the serotonin system holds great potential for the development of new antidepressant therapies.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)