Article
Biochemistry & Molecular Biology
Irina Tolmacheva, Yulia Beloglazova, Mikhail Nazarov, Olga Gagarskikh, Victoria Grishko
Summary: Multidrug resistance (MDR) is a common occurrence in cancer treatment, where cancer cells become resistant to chemotherapy drugs due to overexpression of ATP-binding cassette efflux transporters, including P-glycoprotein (P-gp). A new semi-synthetic derivative, MK, was found to have the highest cytotoxicity against cancer cells, but it was not identified as a P-gp inhibitor or substrate. Further studies suggest that the cytotoxic effect of MK on cancer cells may be induced through the ROS-mediated mitochondrial pathway.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Medicinal
Dogukan Doyduk, Burak Derkus, Buse Sari, Cemil Can Eylem, Emirhan Nemutlu, Yilmaz Yildirir
Summary: In recent years, drugs containing boronic acid groups have shown increased activity in the treatment of bone marrow cancer. This study designed and synthesized boron-containing derivatives of fingolimod, and found that they significantly inhibit cell proliferation and induce apoptosis-mediated cell death in several types of cancer cells. Compared to the commonly used anticancer drug 5-fluorouracil, the boron-containing fingolimod compounds showed significantly enhanced anticancer effects.
ARCHIV DER PHARMAZIE
(2023)
Article
Engineering, Biomedical
Xiaotong Chen, Junxiang Gu, Le Sun, Wenya Li, Lili Guo, Zhiyang Gu, Litong Wang, Yan Zhang, Wangwang Zhang, Baoqin Han, Jing Chang
Summary: Nanocarriers, using vitamin E derivatives, are a promising strategy for cancer drug delivery, overcoming multi-drug resistance and achieving controlled drug release.
BIOACTIVE MATERIALS
(2021)
Review
Biochemistry & Molecular Biology
Jaewan Jeon, Sungmin Lee, Hyunwoo Kim, Hyunkoo Kang, HyeSook Youn, Sunmi Jo, BuHyun Youn, Hae Yu Kim
Summary: This article discusses the anticancer effects and advantages of platinum-based drugs used in the treatment of brain tumors, and summarizes their clinical application cases and limitations. To overcome these obstacles, a novel approach to enhance the effectiveness of platinum-based drugs is emphasized.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Sijongesonke Peter, Sibusiso Alven, Rejoice Bethusile Maseko, Blessing Atim Aderibigbe
Summary: The scarcity of effective cancer therapeutics is a pressing issue. Doxorubicin, currently used in cancer treatment, is limited by drug resistance and toxicity. Combination with other chemotherapeutic agents is considered an effective treatment option.
Article
Chemistry, Medicinal
Qian Yu, Qiongna Cai, Wanxin Liang, Kewen Zhong, Jiayong Liu, Haizhou Li, Yongzhi Chen, Hongxia Li, Shanfang Fang, Rongcui Zhong, Shouping Liu, Shuimu Lin
Summary: This study reports the synthesis and biological evaluation of cationic amphiphilic phenothiazine-based derivatives. The most promising compound, 30, displayed potent bactericidal activity against both Gram-positive and Gram-negative bacteria, low cytotoxicity towards mammalian cells, excellent salt resistance, and showed potent in vivo efficacy in a murine model of bacterial keratitis. Compound 30 has a promising prospect as a broad-spectrum antibacterial agent for the treatment of drug-resistant bacterial infections.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biotechnology & Applied Microbiology
L. Aguilar-Vega, L. E. Lopez-Jacome, B. Franco, S. Munoz-Carranza, N. Vargas-Maya, R. Franco-Cendejas, M. Hernandez-Duran, M. Otero-Zuniga, C. Campo-Beleno, J. G. Jimenez-Cortes, M. Martinez-Vazquez, J. S. Rodriguez-Zavala, T. Maeda, R. Zurabian, R. Garcia-Contreras
Summary: The study demonstrates that phenothiazine derivatives, especially chlorpromazine, exhibit attractive antibacterial properties against nosocomial multidrug-resistant strains of A. baumannii by generating reactive oxygen species (ROS) and causing cell membrane and DNA damage. Chlorpromazine also shows synergy with various antibiotics and is effective in treating experimentally infected Galleria mellonella when combined with ceftazidime. Repurposing phenothiazine derivatives for treating resistant infections by A. baumannii shows promising potential.
JOURNAL OF APPLIED MICROBIOLOGY
(2021)
Article
Pharmacology & Pharmacy
Laura Gallego-Yerga, Valentin Cena, Rafael Pelaez
Summary: The use of benzothiazole scaffold in designing colchicine site ligands has resulted in a new family of ligands with high water solubility. These ligands exhibit antiproliferative activity against various cancer cell lines, with high selectivity towards cancer cells. The most potent derivatives show nanomolar range IC50 values, even in difficult-to-treat glioblastoma cells. Flow cytometry experiments and confocal microscopy observations confirm the cell cycle arrest and apoptotic cell death induced by these ligands, which are attributed to their ability to disrupt microtubule network. Docking studies further support the interaction of the ligands at the colchicine binding site. These results validate the effective strategy of developing potent anticancer colchicine ligands with improved water solubility.
Review
Biochemistry & Molecular Biology
Adelina Lombrea, Alexandra Denisa Scurtu, Stefana Avram, Ioana Zinuca Pavel, Maris Turks, Jevgenija Luginina, Uldis Peipins, Cristina Adriana Dehelean, Codruta Soica, Corina Danciu
Summary: Clinical trials have shown that natural compounds can be effective in managing cancer, serving as starting points for new drug development. Betulonic acid and its derivatives have potential as anticancer agents, but more research is needed to fully understand their mechanisms and efficacy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Cheng-Yao Yang, Min-Yu Lee, Yeh-Long Chen, Jun-Ping Shiau, Yung-Hsiang Tsai, Chia-Ning Yang, Hsueh-Wei Chang, Chih-Hua Tseng
Summary: A series of 4-anilinoquinolinylchalcone derivatives were synthesized and evaluated for their antiproliferative activities. Among them, compound 4a showed the highest cytotoxicity in breast cancer cells and low cytotoxicity in normal cells. Compound 4a caused ATP depletion, apoptosis, and ROS-dependent caspase 3/7 activation in breast cancer cells. These findings suggest that 4-anilinoquinolinylchalcone derivatives have potential as anticancer agents.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Olesya Voronova, Sergey Zhuravkov, Elena Korotkova, Anton Artamonov, Evgenii Plotnikov
Summary: Phenothiazine and its derivatives were studied for their antioxidant activity, and optimal conditions for manifestation of this activity were found. The research showed that phenothiazine derivatives have potential antioxidant properties, which is important for developing complex preparations with antioxidant activity, including in psychiatric practice.
Review
Biochemistry & Molecular Biology
Marta Szumilak, Anna Wiktorowska-Owczarek, Andrzej Stanczak
Summary: Hybrid drugs targeting multiple points of cancer cells have been extensively explored in recent years. They possess simpler pharmacokinetic profiles, reduce the possibility of drug interactions, and facilitate the drug development process.
Article
Chemistry, Multidisciplinary
Hulya Gizem Ozkan, Vanrajsinh Thakor, Hong-Gui Xu, Galyna Bila, Rostyslav Bilyy, Daria Bida, Martin Boettcher, Dimitrios Mougiakakos, Rainer Tietze, Andriy Mokhir
Summary: Elevated levels of reactive oxygen species (ROS) and deficient mitochondria are weak points of cancer cells. Designing highly potent anticancer drugs that target both ROS and mitochondria is a valid therapeutic strategy. However, limiting the drug effects to cancer cells without affecting normal ones remains a challenge. In this study, we developed novel aminoferrocene derivatives that are chemically stable in the presence of ROS, generate mitochondrial ROS in cancer cells but not normal cells, and exhibit anticancer effects in vivo.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Thidarath Rattanaburee, Patpanat Sermmai, Kornthip Tangthana-umrung, Tienthong Thongpanchang, Potchanapond Graidist
Summary: This study investigated the cytotoxicity and anticancer activity of (+/-)-kusunokinin derivatives on various cancer cells. The results showed that (+/-)-TTPG-B exhibited the strongest cytotoxicity on breast cancer and cholangiocarcinoma cells. Both (+/-)-TTPG-A and (+/-)-TTPG-B induced cell cycle arrest and apoptosis, and their effects were superior to (+/-)-kusunokinin.
Review
Biochemistry & Molecular Biology
Yingqian Zhang, Chenyuan Wu, Nana Zhang, Rui Fan, Yang Ye, Jun Xu
Summary: Pyrazole derivatives, a class of heterocyclic compounds, possess unique chemical structures and exhibit a broad spectrum of pharmacological activities. Recent studies have focused on synthesizing and evaluating pyrazole derivatives for their anticancer potential. Structure-activity relationship studies have shown that appropriate substitution on the pyrazole ring can enhance anticancer efficacy and selectivity. Furthermore, these derivatives have demonstrated multiple mechanisms of anticancer action, making them promising candidates for developing anticancer drugs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Angela Rampa, Silvia Gobbi, Federica Belluti, Alessandra Bisi
Summary: The unmet need for effective drugs for Alzheimer's disease is a major challenge in drug discovery. Drug repurposing has become an attractive approach to obtain new medications and reduce time and economic burden. Different classes of drugs show promising effects on neurodegenerative diseases, with structural modifications resulting in multifunctional compounds.
CURRENT MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Jessica Caciolla, Giovanna Picone, Giovanna Farruggia, Dario Valenti, Angela Rampa, Emil Malucelli, Federica Belluti, Alfonso Trezza, Ottavia Spiga, Stefano Iotti, Silvia Gobbi, Concettina Cappadone, Alessandra Bisi
Summary: In this study, a new library of derivatives with a polycyclic scaffold was designed and synthesized as potential MDR reverting agents and antitumor agents. The research focused on the role of the spacer connecting the polycyclic core with nitrogen-containing groups, leading to the discovery of compounds with significant reverting potency. Additionally, these compounds exhibited multifaceted anticancer properties and dual in vitro activity, showing both revertant and antitumor effects.
BIOORGANIC CHEMISTRY
(2021)
Review
Biochemistry & Molecular Biology
Silvia Gobbi, Federica Belluti, Angela Rampa, Alessandra Bisi
Summary: Naturally occurring flavonoids are bioactive compounds found in plants, used for treating various pathologies. They are considered valuable sources for lead compounds and synthetic compounds development. There has been a renewed interest in flavonoid-based structures, particularly in anticancer research.
Article
Biochemistry & Molecular Biology
Serena Montanari, Marco Allara, Laura Scalvini, Magdalena Kostrzewa, Federica Belluti, Silvia Gobbi, Marina Naldi, Silvia Rivara, Manuela Bartolini, Alessia Ligresti, Alessandra Bisi, Angela Rampa
Summary: Recent studies have revealed the connection between the endocannabinoid system (eCS) and neuroprotection, suggesting its involvement in regulating cognitive processes and the pathophysiology of Alzheimer's disease. Designed and synthesized coumarin-based compounds showed promising potential as multitarget agents for combating complex diseases like AD.
Article
Chemistry, Medicinal
Jessica Caciolla, Silvia Martini, Angelo Spinello, Matic Pavlin, Eleonora Turrini, Federica Simonelli, Federica Belluti, Angela Rampa, Alessandra Bisi, Carmela Fimognari, Nadia Zaffaroni, Silvia Gobbi, Alessandra Magistrato
Summary: Breast cancer is a major cause of death in women globally, and the development of dual acting molecules targeting aromatase and estrogen receptor alpha may provide a promising alternative strategy to combat estrogen receptor positive breast cancer. This study identifies key structural features needed for optimal dual acting drug candidates, demonstrating the potential of multitarget compounds as a viable therapeutic option for ER+ BC.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Martina Rossi, Concettina Cappadone, Giovanna Picone, Alessandra Bisi, Giovanna Farruggia, Federica Belluti, Paolo Blasi, Silvia Gobbi, Emil Malucelli
Summary: This study reports a series of new compounds with anti-osteosarcoma activity. The antitumor activity, cell cycle progression, and apoptosis induction of these compounds were evaluated using innovative techniques and methods. Among the tested compounds, 1e, 1q, and 1r showed the most promising antitumor properties.
Article
Chemistry, Medicinal
Jessica Caciolla, Silvia Martini, Angelo Spinello, Federica Belluti, Alessandra Bisi, Nadia Zaffaroni, Alessandra Magistrato, Silvia Gobbi
Summary: This study developed a new generation of dualsteric non-steroidal aromatase inhibitors (AIs) and conducted extensive structural characterization at the molecular level. The most active inhibitor was found to effectively lock onto the enzyme's active site, overcoming resistance issues encountered in treatment.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Francesca Seghetti, Federica Belluti, Angela Rampa, Silvia Gobbi, Jenny Legac, Silvia Parapini, Nicoletta Basilico, Alessandra Bisi
Summary: The study focused on designing a series of hybrid molecules to combat malaria, with compounds 1b and 1c showing the highest in vitro activity, particularly against resistant strains of Plasmodium falciparum.
FUTURE MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Silvia Gobbi, Silvia Martini, Riccardo Rozza, Angelo Spinello, Jessica Caciolla, Angela Rampa, Federica Belluti, Nadia Zaffaroni, Alessandra Magistrato, Alessandra Bisi
Summary: In this study, novel compounds with dual AR and ER activity were designed by modifying flavonoid-related compounds. Compounds 3b and 4a showed promising submicromolar activity against both targets. Computational studies confirmed the feasibility of using multi-target approaches for ER+ BC treatment. The homoisoflavone core emerged as a valuable scaffold for the design of multifunctional compounds.