Review
Biochemistry & Molecular Biology
Maniyamma Aswathy, Ajesh Vijayan, Uzini D. Daimary, Sosmitha Girisa, Kokkuvayil Radhakrishnan, Ajaikumar B. Kunnumakkara
Summary: Natural products, particularly phytochemicals, have emerged as potential candidates for the development of anticancer drugs due to their structural diversities and pleiotropic effects. This article discusses betulinic acid (BA), a widely distributed natural compound, as a promising agent for the prevention and treatment of various human malignancies. The review provides insights into the mechanistic framework and key outcomes of BA in cancer suppression through modulation of multiple signaling pathways.
JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Marie Kozubek, Sophie Hoenke, Theresa Schmidt, Hans-Peter Deigner, Ahmed Al-Harrasi, Rene Csuk
Summary: Betulin and betulinic acid derived 30-oxo-amides were synthesized and screened for cytotoxic activity. All compounds showed significant cytotoxicity against various human tumor cell lines. Structural modifications resulted in different cytotoxicity, with compounds 11 and 12, which contained an additional ethylenediamine moiety, exhibiting low EC50 values and predominantly inducing apoptosis.
Article
Biochemistry & Molecular Biology
Justyna Kutkowska, Leon Strzadala, Andrzej Rapak
Summary: Betulinic acid and betulin have shown promising activity against cancer cells, inhibiting viability and proliferation of non-small cell lung cancer (NSCLC) cells under normoxic and hypoxic conditions. The treatment induces G1 cell cycle arrest and increases apoptosis in NSCLC cells, with downregulation of the Wnt/beta-catenin pathway and deregulation of HIF-1 alpha and p53 expression levels observed. Additionally, betulinic acid reduces clonogenic activity under hypoxia, suggesting new strategies for treating hypoxic cancer tumors.
CHEMICO-BIOLOGICAL INTERACTIONS
(2021)
Article
Infectious Diseases
Ruqaiyyah Siddiqui, Noor Akbar, Bushra Khatoon, Muhammad Kawish, Muhammad Shaiq Ali, Muhammad Raza Shah, Naveed Ahmed Khan
Summary: Due to global warming and global water shortages, infections caused by free-living amoebae such as Acanthamoeba are expected to increase. This study extracted and isolated plant-based secondary metabolites as novel disinfectants against pathogenic Acanthamoeba. The compounds showed anti-Acanthamoebic properties, inhibited encystation and excystation processes, and significantly inhibited Acanthamoeba's binding capability to host cells.
Article
Immunology
Ivan N. N. Koshkin, Vasily S. S. Vlasenko, Valentina I. I. Pleshakova, Larisa E. E. Alkhimova, Andrey V. V. Elyshev, Ivan V. V. Kulakov
Summary: This study investigated the morphological changes in the lymphoid tissue associated with the bronchial mucosa lungs (BALT) in a guinea pig model of experimental tuberculosis using conjugates based on BCG antigens with betulin and its derivatives. The results showed a significant decrease in the BALT response and an increase in the number of plasma cells in the lung tissues of guinea pigs treated with these conjugates.
Article
Plant Sciences
Payamnoor Vahide, Khodadadi Negar, Jafari Hajati Razieh
Summary: This study developed a protocol for callus induction and evaluated the effects of different nano fibers on betulin and betulinic acid production in stem cells of a hybrid of Betula pendula. The results showed that CTS-N increased the weight of calli, CT-N and Cellul-N significantly influenced the accumulation of betulin and betulinic acid. Additionally, CTS-N exhibited high antioxidant activity.
SOUTH AFRICAN JOURNAL OF BOTANY
(2021)
Article
Chemistry, Medicinal
Oliver Kraft, Marie Kozubek, Sophie Hoenke, Immo Serbian, Daniel Major, Rene Csuk
Summary: Safirinium P and Q fluorescence labels were synthesized and conjugated with spacered triterpenoic acids to access hybrid structures. While the parent safirinium compounds were not cytotoxic at all, many triterpenoid safirinium P and Q conjugates showed moderate cytotoxicity, with one compound demonstrating low cytotoxicity in both malignant and non-malignant cells, indicating potential therapeutic activity.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Anna Hordyjewska, Monika Prendecka-Wrobel, Lukasz Kurach, Anna Horecka, Anna Olszewska, Dominika Pigon-Zajac, Teresa Malecka-Massalska, Jacek Kurzepa
Summary: Electric cell-substrate impedance sensing was used to investigate the anticancer activities of betulin and betulinic acid. The results showed that these compounds have potential antitumor properties and little toxicity to healthy cells.
Article
Biochemistry & Molecular Biology
Arkadiusz Orchel, Ewa Chodurek, Marzena Jaworska-Kik, Piotr Paduszynski, Anna Kaps, Elwira Chrobak, Ewa Bebenek, Stanislaw Boryczka, Paulina Borkowska, Janusz Kasperczyk
Summary: In this study, it was found that 30-diethoxyphosphoryl-28-propynoylbetulin displayed the strongest inhibitory effect on growth and induction of cellular death in human breast cancer cells. The compound decreased DNA synthesis, up-regulated p21(WAF1/Cip1) levels, increased cell death, and triggered reactive oxygen species generation and mitochondrial membrane potential loss, ultimately leading to a form of regulated cell demise that exhibits features of necrosis-like morphology and activation of caspases.
Article
Chemistry, Multidisciplinary
Marie Kozubek, Sophie Hoenke, Hans-Peter Deigner, Rene Csuk
Summary: New analogues of pentacyclic triterpene-piperazine-rhodamine B conjugates were synthesized from betulinic acid or glycyrrhetinic acid, and their cytotoxic activity was examined. The results showed that the linking position at ring E determines the magnitude of cytotoxicity. These conjugates were highly cytotoxic, acting as necrotic compounds and mitocans.
RESULTS IN CHEMISTRY
(2022)
Article
Food Science & Technology
Jeronimo Laiolo, Cecilia L. Barbieri, Mariana B. Joray, Priscila A. Lanza, Sara M. Palacios, D. Mariano A. Vera, Maria C. Carpinella
Summary: The study identified betulin as an effective agent to inhibit P-gp-mediated multidrug resistance, increasing intracellular accumulation of anticancer drugs and sensitizing MDR leukemia cells to Dox. Docking studies revealed betulin's tight binding to key regions of P-gp, mimicking tariquidar's contacts without toxicity. These findings suggest that betulin may be a promising candidate for developing more effective and less toxic chemotherapy agents.
FOOD AND CHEMICAL TOXICOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Marina Petrenko, Antje Guttler, Anne Funtan, Jacqueline Kessler, Daniel Emmerich, Reinhard Paschke, Dirk Vordermark, Matthias Bache
Summary: The study demonstrates that the combination therapy of the novel betulin derivative 3-AC and a CAI, such as OCT or SLC-0111, can significantly enhance radiosensitivity, increase cytotoxicity, inhibit cell motility, and enhance DNA damage in hypoxic tumor cells. This approach shows promise as a potential therapeutic strategy for targeting resistant hypoxic tumor cells.
CHEMICO-BIOLOGICAL INTERACTIONS
(2021)
Review
Biochemistry & Molecular Biology
Jan Bachorik, Milan Urban
Summary: Pentacyclic triterpenes, important natural products with diverse biological activities, show potential as medicines for cancer and infections. Their natural forms have limitations, requiring modifications through organic synthesis or biocatalysis for drug development. Biocatalysis, while less utilized than organic synthesis, is gaining interest for future applications.
Article
Pharmacology & Pharmacy
Zhihao Liu, Xiaozhou Wen, Guangji Wang, Ying Zhou
Summary: 23-HBA significantly enhances the efficacy of anti-tumor agents in MDR cells, related to P-gp inhibition. Experimental results demonstrate that 23-HBA can improve cytotoxicity of ADR and VCR in MDR cells and affect the transport of P-gp substrates.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biotechnology & Applied Microbiology
Yong Li, Yixuan Wang, Lun Gao, Yinqiu Tan, Jiayang Cai, Zhang Ye, Ann T. Chen, Yang Xu, Linyao Zhao, Shiao Tong, Qian Sun, Baohui Liu, Shenqi Zhang, Daofeng Tian, Gang Deng, Jiangbing Zhou, Qianxue Chen
Summary: This study successfully synthesized betulinic acid nanoparticles (BA NPs) that can cross the blood-brain barrier and demonstrated strong anti-tumor effects. In vitro experiments showed that BA NPs could inhibit glioma cell proliferation, induce apoptosis, and block the cell cycle. In vivo experiments in mice with intracranial GBM xenografts showed that BA NPs could effectively cross the blood-brain barrier and significantly prolong the survival time of the mice.
JOURNAL OF NANOBIOTECHNOLOGY
(2022)
Article
Cell Biology
Wojciech Szlasa, Sylwester Slusarczyk, Izabela Nawrot-Hadzik, Renata Abel, Aleksandra Zalesinska, Anna Szewczyk, Natalia Sauer, Robert Preissner, Jolanta Saczko, Marcin Drag, Marcin Poreba, Malgorzata Daczewska, Julita Kulbacka, Malgorzata Drag-Zalesinska
Summary: Betulinic acid and betulin are compounds with anti-inflammatory properties and have the potential to reduce inflammation by reducing IL-6 secretion. They have minimal effect on COX-2 activity. Bet-Orn and Bet-Lys are highly cytotoxic and induce the aggregation of IFN gamma R. Bet-Lys has a higher degree of inhibition on COX-2 activity than dexamethasone. Bet-Orn is the only compound that increases the content of HSP-70 in macrophages. All compounds are more effective than dexamethasone in reducing IL-6.
Article
Multidisciplinary Sciences
Wojciech Szlasa, Olga Michel, Natalia Sauer, Vitalij Novickij, Damian Lewandowski, Paulina Kasperkiewicz, Mounir Tarek, Jolanta Saczko, Julita Kulbacka
Summary: This study investigates the effects of nanosecond pulsed electric fields (nsPEF) on pancreatic cancer cells and their mechanisms of action. It reveals that nsPEF treatment leads to the release of microvesicles, enhanced electropermeabilization, and cell shrinkage. It also shows that nsPEF treatment reduces tumor spheroid size and proposes a mechanism involving cell membrane surface tension and actin fiber organization.
SCIENTIFIC REPORTS
(2023)
Article
Chemistry, Multidisciplinary
Joanna Tunikowska, Nina Rembialkowska, Olga Michel, Justyna Maczynska, Agnieszka Antonczyk, Przemyslaw Przadka, Zdzislaw Kielbowicz, Julita Kulbacka
Summary: This study proposes the combination of indocyanine green (ICG) with bleomycin (BLM) for electrochemotherapy (ECT), which allows for drug distribution control and detection. The method was validated through in vitro and in vivo experiments, demonstrating its safety and effectiveness.
APPLIED SCIENCES-BASEL
(2023)
Review
Biochemistry & Molecular Biology
Julia Karska, Szymon Kowalski, Jolanta Saczko, Mihaela G. G. Moisescu, Julita Kulbacka
Summary: Mechanical forces are essential elements in the world around us, and they have observable effects at both macro and molecular levels. The presence of mechanosensitive ion channels (MIChs), such as the Piezo and TRP families, plays a major role in the tissues and cells of animals, contributing to various physiological processes in the human body. Recent research has also connected these channels to the development of malignant tumors.
Article
Engineering, Biomedical
Zbigniew Raszewski, Katarzyna Chojnacka, Julita Kulbacka, Marcin Mikulewicz
Summary: The aim of this study was to develop a 3D printing material with bioactive properties for producing transparent removable orthodontic appliances. By adding four bioactive glasses at 10% concentration to acrylic monomers, ions such as Ca, P, Si, and F were released. The printed materials were tested for various properties including flexural strength, sorption and solubility, ion release, and cytotoxicity. The results showed that the material released Ca2+ and PO43- ions for 42 days and had good flexural strength in certain orientations. Furthermore, cell survival rate was high after exposure to the material.
JOURNAL OF FUNCTIONAL BIOMATERIALS
(2023)
Article
Biochemistry & Molecular Biology
Julita Kulbacka, Anna Choromanska, Anna Szewczyk, Olga Michel, Dagmara Baczynska, Andrzej Sikora, Joanna Rossowska, Marek Kulbacki, Nina Rembialkowska
Summary: Ultrashort electric pulses in the nanosecond range can affect cell structures and functioning by altering calcium levels. This study examined the impact of nsPEFs combined with calcium on human colon adenocarcinoma cell lines. The results showed that nsPEF with calcium was cytotoxic for drug resistant cancer cells and safe for normal cells. The treatment also caused oxidative stress and altered cell morphology.
BIOELECTROCHEMISTRY
(2023)
Review
Biochemistry & Molecular Biology
Agnieszka Gajewska-Naryniecka, Urszula Szwedowicz, Zofia Lapinska, Julia Rudno-Rudzinska, Wojciech Kielan, Julita Kulbacka
Summary: Pancreatic cancer is a silent and aggressive disease that only shows symptoms in advanced stages. The only curative treatment is surgical resection, but irreversible electroporation (IRE) offers hope for patients with unresectable tumors. IRE is an ablation therapy that uses high-voltage electrical pulses to destroy cancer cells. This review summarizes the applications and potential of IRE in treating pancreatic cancer, including its combination with drugs or standard treatments. However, further research is needed to assess its effectiveness in humans and understand its full potential.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Szymon Kowalski, Julia Karska, Zofia Lapinska, Bartosz Hetnal, Jolanta Saczko, Julita Kulbacka
Summary: Regulated cell death is a vital and diverse process in organism's life cycle, involving embryonic development, aging, homeostasis regulation, and organ maintenance. This review aims to present the latest literature on pyroptosis and apoptosis, and compare their molecular pathway elements and significance in organism's physiology and pathophysiology.
JOURNAL OF CELLULAR BIOCHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Ewa Sawicka, Julita Kulbacka, Malgorzata Drag-Zalesinska, Arkadiusz Wozniak, Agnieszka Piwowar
Summary: The number of risk factors for breast cancer is increasing, including estrogens and interaction with toxic chromium(VI). The study investigated the effects of estrogens and Cr(VI) on cell viability and DNA damage. The results showed that 17 beta-E2 had a protective effect against Cr(VI)-induced cytotoxicity.
Article
Chemistry, Physical
Zbigniew Raszewski, Julita Kulbacka, Daria Pakula, Dariusz Brzakalski, Robert E. Przekop
Summary: This study aimed to investigate the use of PMMA modified with a silanized feldspar filler for the production of prosthetic teeth. The addition of feldspar significantly improved the compressive strength of the material, and the composite teeth showed good adhesion to the denture plate. The materials were determined to be biocompatible and safe for treated cells, with increased cell viability observed.
Article
Pharmacology & Pharmacy
Eivina Radzeviciute-Valciuke, Jovita Gecaite, Augustinas Zelvys, Aukse Zinkeviciene, Rokas Zalneravicius, Veronika Malysko-Ptasinske, Ausra Nemeikaite-Ceniene, Vytautas Kaseta, Natalija German, Jurij Novickij, Almira Ramanaviciene, Julita Kulbacka, Vitalij Novickij
Summary: This study demonstrates that MHz frequency bursts of nanosecond pulses can enhance gene delivery and investigates the potential of gold nanoparticles in this process. The combination of microsecond pulses and gold nanoparticles significantly improves gene delivery, depending on the surface charge and size of the nanoparticles. Gold nanoparticles are ineffective in nanosecond pulse treatment, but MHz pulse treatment remains competitive, with high gene delivery efficiency, low reactive oxygen species generation, preserved cellular viability, and easier operation.
Article
Chemistry, Medicinal
Katarzyna Biezunska-Kusiak, Julita Kulbacka, Anna Choromanska, Nina Rembialkowska, Olga Michel, Jolanta Saczko
Summary: Breast cancer is one of the most common malignant neoplasms in Poland. The use of calcium ion-assisted electroporation has been proven effective in recent studies. This research aimed to investigate the antitumor effects of electroporation and calcium ion-assisted electroporation on human mammary adenocarcinoma cells. The obtained results confirmed the effectiveness of the investigated therapeutic method, providing a basis for further in vivo research and the development of a more effective and safer treatment for breast cancer patients.
Article
Pharmacology & Pharmacy
Nina Rembialkowska, Vitalij Novickij, Eivina Radzeviciute-Valciuke, Egle Mickeviciute, Agnieszka Gajewska-Naryniecka, Julita Kulbacka
Summary: Electrochemotherapy combines anticancer drugs with electroporation to overcome drug resistance in cancer. The study found that different drug combinations can have synergistic effects and that nanosecond pulses provide more flexibility in cancer cell death.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2023)
Article
Biology
Wojciech Szlasa, Natalia Sauer, Kamila Wala, Jolanta Saczko, Julita Kulbacka
Summary: This article investigates how single amino acid mutations impact the structure and function of proteins, and discusses the methods used to derive higher-level protein structures from amino acid sequences. The study aims to explain the interactions within polypeptide organization and their clinical implications.
POSTEPY BIOLOGII KOMORKI
(2022)
Article
Chemistry, Medicinal
Shibin Zhao, Julian Maceren, Mia Chung, Samantha Stone, Raphael Geiben, Melissa L. Boby, Bradley S. Sherborne, Derek S. Tan
Summary: Antibiotic resistance is a major threat to public health, with Gram-negative bacteria presenting unique challenges due to their low permeability and efflux pumps. Limited understanding of the chemical rules for overcoming these barriers hinders antibacterial drug discovery. Efforts to address this issue, such as screening compound libraries and using cheminformatic analysis, have led to the design of sulfamidoadenosines with diverse substituents, showing potential utility in accumulation in Escherichia coli.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Jichun Li, Qing Li, Shuai Xia, Jiahuang Tu, Longbo Zheng, Qian Wang, Shibo Jiang, Chao Wang
Summary: This study successfully developed a short peptide mimetic as a MERS-CoV fusion inhibitor by reproducing the key recognition features of the HR2 helix. The resulting 23-mer lipopeptide showed comparable inhibitory effect to the 36-mer HR2 peptide HR2P-M2. This has important implications for developing short peptide-based antiviral agents to treat MERS-CoV infection.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Krista Jaunsleine, Linda Supe, Jana Spura, Sten van Beek, Anna Sandstrom, Jessica Olsen, Carina Halleskog, Tore Bengtsson, Ilga Mutule, Benjamin Pelcman
Summary: Beta(2)-adrenergic receptor agonists can stimulate glucose uptake by skeletal muscle cells and are therefore potential treatments for type 2 diabetes. The chirality of compounds has a significant impact on the activity of these agonists. This study found that certain synthesized compounds showed higher glucose uptake activity. These findings provide important information for the design of novel beta(2)AR agonists for T2D treatment.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Xin Xu, Jia Chen, Guan Wang, Xiaojuan Zhang, Qiang Li, Xiaobo Zhou, Fengying Guo, Min Li
Summary: The study focuses on EZH2, a promising therapeutic target for various types of cancers. Researchers designed and synthesized a series of novel derivatives aiming to enhance the EZH2 inhibition activity. Among them, compound 28 displayed potent EZH2 inhibition activity and showed high anti-proliferative effects in lymphoma cell lines and xenograft mouse models. The study suggests that compound 28 has potential as a therapeutic candidate for EZH2-associated cancers.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Wei Zhang, Wei Liu, Ya-Dong Zhao, Li-Zi Xing, Ji Xu, Rui-Jun Li, Yun-Xiao Zhang
Summary: This study developed a series of aromatic amide derivatives based on Rhein and investigated their inhibitory activity against alpha-Syn aggregation. Two of these compounds showed promising potential in treating Parkinson's disease by stabilizing alpha-Syn's conformation and disassembling alpha-Syn oligomers and fibrils.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Mani Sharma, S. S. S. S. Sudha Ambadipudi, Neeraj Kumar Chouhan, V. Lakshma Nayak, Srihari Pabbaraja, Sai Balaji Andugulapati, Ramakrishna Sistla
Summary: Therapeutically active lipids in drug delivery systems can enhance the safety and efficacy of treatment. The liposome formulation created using synthesized biologically active lipids showed additive anti-cancer effects and reduced tumorigenic potential.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
