Article
Chemistry, Multidisciplinary
Jelena Vasiljeva, Marina Makrecka-Kuka, Ilona Domracheva, Karlis Vilks, Pavels Dimitrijevs, Pavel Arsenyan
Summary: This study reports the design and synthesis of novel selenophenoquinolinones and their ability to reverse doxorubicin resistance in uterus sarcoma cells. Compound 5e demonstrated the best cytotoxicity and attenuated cell resistance to doxorubicin by inhibiting ABCB1 transporter activity and suppressing ABCB1 gene expression.
NEW JOURNAL OF CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Mohamed A. Morsy, Mahmoud Kandeel, Ahmed R. N. Ibrahim, Seham A. Abdel-Gaber, Shery Jacob, Katharigatta N. Venugopala, Pottathil Shinu, Mahmoud El-Daly
Summary: Carnosine was found to be a potential inhibitor of P-gp activity and potentiate doxorubicin-induced cytotoxicity, providing a potential beneficial role in the treatment of multidrug-resistant cancers.
Article
Biochemistry & Molecular Biology
Safiulla Basha Syed, Shu-Yu Lin, Hemant Arya, I-Hsuan Fu, Teng-Kuang Yeh, Mariasoosai Ramya Chandar Charles, Latha Periyasamy, Hsing-Pang Hsieh, Mohane Selvaraj Coumar
Summary: P-glycoprotein (P-gp) inhibitors have the potential to reverse multidrug resistance and enhance the efficacy of chemotherapy drugs, but currently there are no approved P-gp inhibitors for clinical use; this study identified two potential P-gp inhibitors with lower toxicity and cross-reactivity, showing promise for further in vivo investigations.
CHEMICAL BIOLOGY & DRUG DESIGN
(2021)
Article
Pharmacology & Pharmacy
Xin-li Liang, Miao-miao Ji, Zheng-gen Liao, Guo-wei Zhao, Xi-lan Tang, Wei Dong
Summary: The study investigates the reversal effects of imperatorin (IMP) on drug resistance in leukemia cells and mice. The results show that IMP can enhance the cytotoxicity of chemotherapy drugs and reduce the expression of P-gp. In addition, IMP can inhibit the metabolism of cells, thereby enhancing the anti-tumor effect of chemotherapy drugs.
KOREAN JOURNAL OF PHYSIOLOGY & PHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Yao-Yuan Chang, Hung-Jun Lin, Ling-Chi Hsiao, Yu-Feng Lin, Chih-Sheng Chang, Der-Zen Liu
Summary: The combination therapy of DTX or DOX with TG1 enhances drug efficacy by suppressing the p-glycoprotein efflux pump, suggesting potential use for breast cancer patients, especially those with multidrug resistance.
Article
Oncology
Sharad S. Singhal, Atish Mohanty, Prakash Kulkarni, David Horne, Sanjay Awasthi, Ravi Salgia
Summary: Inhibiting RLIP shows promise in treating melanoma, as it plays a key role in melanoma cell survival. By targeting RLIP, wide-spectrum agents can be developed for cancer therapy independent of common signaling pathway mutations.
Article
Chemistry, Medicinal
T. A. Fedotcheva, N. L. Shimanovsky
Summary: The mechanisms of multidrug resistance (MDR) in chemotherapy for cancer are discussed in this review, involving ABC-transporters like P-glycoprotein, BCRP protein, and MRP proteins. The review introduces the main classes of chemosensitizers, which belong to the 1st to 4th generations of ABC transporter inhibitors. Plant polyphenols, specifically flavonoids, are identified as the latest (4th) generation MDR inhibitors. The selection of chemosensitizers from different classes should consider the patient's mutation-expression profile and receptor status of their tumor, while appropriate dosage and administration schedule can enhance the counteraction of MDR.
PHARMACEUTICAL CHEMISTRY JOURNAL
(2023)
Article
Chemistry, Medicinal
Stepan K. Krymov, Alexander M. Scherbakov, Lyubov G. Dezhenkova, Diana I. Salnikova, Svetlana E. Solov'eva, Danila V. Sorokin, Daniela Vullo, Viviana De Luca, Clemente Capasso, Claudiu T. Supuran, Andrey E. Shchekotikhin
Summary: In this study, new compounds were designed and synthesized to inhibit tumor-associated carbonic anhydrase activity, with some compounds showing high inhibitory activity against specific enzymes and exhibiting selectivity for certain cell lines.
Article
Chemistry, Medicinal
Dan Wang, Duochun Ji, Danni Wu, Like Wang, Chunyan Yu, Chun Li, Xiaodong Gai
Summary: In this study, the researchers investigated the effects of saikosaponin A (SSa) and saikosaponin B (SSb) on doxorubicin-resistant breast cancer cells. They found that SSa and SSb suppressed cell proliferation and enhanced the cytotoxicity of doxorubicin. The compounds also decreased P-glycoprotein expression and induced G1-phase arrest in the cells.
PHARMACOGNOSY MAGAZINE
(2023)
Review
Oncology
Andaleeb Sajid, Hadiar Rahman, Suresh V. Ambudkar
Summary: Cancer cells often develop resistance to anticancer drugs, primarily through the overexpression of ABC transporters. Recent studies on ABCB1, ABCG2, and ABCC1 have provided insights into their structure and function, leading to the development of new therapeutic approaches. It is recommended to use these findings in clinical trials to enhance the efficacy of chemotherapy for cancer patients.
NATURE REVIEWS CANCER
(2023)
Review
Pharmacology & Pharmacy
Kunal S. Taskar, Xinning Yang, Sibylle Neuhoff, Mitesh Patel, Kenta Yoshida, Mary F. Paine, Kim L. R. Brouwer, Xiaoyan Chu, Yuichi Sugiyama, Jack Cook, Joseph W. Polli, Imad Hanna, Yurong Lai, Maciej Zamek-Gliszczynski
Summary: This article discusses the role of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) in drug-drug interactions, drug absorption, and brain penetration. Based on clinical evidence, the article suggests that inhibition of P-gp or BCRP in the liver or kidneys has limited clinical implications on drug disposition.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Nanoscience & Nanotechnology
Neeraj Kaushal, Zhe-Sheng Chen, Senshang Lin
Summary: The study evaluates double-coated PBCA-NPs as a potential carrier system for overcoming MDR in cancer cells mediated by P-gp and BCRP. Results showed that double-coated PBCA-NPs significantly enhanced cellular uptake of doxorubicin and improved sensitivity in P-gp and BCRP overexpressing cell lines, suggesting their potential for enhancing drug accumulation in MDR cancer cells.
FRONTIERS IN NANOTECHNOLOGY
(2021)
Article
Chemistry, Medicinal
Catharina Holtschulte, Frederik Boergel, Stefanie Westphaelinger, Dirk Schepmann, Gianluca Civenni, Erik Laurini, Domenico Marson, Carlo Catapano, Sabrina Pricl, Bernhard Wunsch
Summary: A series of novel sigma(1) receptor ligands with improved lipophilic ligand efficiency were synthesized and evaluated. Different amino substituents in the piperidine scaffold were found to affect sigma(1) receptor affinity. The study also revealed the interaction mechanism between the piperidine ligands and the receptor.
Article
Chemistry, Multidisciplinary
Mei Cong, Guangling Xu, Shaoyou Yang, Jing Zhang, Wenzheng Zhang, Dinesh Dhumal, Erik Laurini, Kaiyue Zhang, Yi Xia, Sabrina Pricl, Ling Peng, Weidong Zhao
Summary: This study reports a self-assembling prodrug nanosystem of the anticancer drug gemcitabine. The prodrug exhibits high drug loading and self-assembles into small nanomicelles, enabling entry into cells and responsive drug release. The system shows enhanced anticancer activity and reduced toxicity, making it a promising candidate for cancer treatment. The study also offers new perspectives for the development of self-assembling prodrugs using amphiphilic dendrimer nanoplatforms.
CHINESE CHEMICAL LETTERS
(2022)
Review
Pharmacology & Pharmacy
Maria Russi, Domenico Marson, Alice Fermeglia, Suzana Aulic, Maurizio Fermeglia, Erik Laurini, Sabrina Pricl
Summary: BRCA1 and BARD1 play crucial roles in various biological functions, but mutations in their encoding genes increase the risk of developing cancer and other malignancies. Understanding their functional mechanisms not only helps prevent disease occurrences but also facilitates the development of new targeted therapeutics.
PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Medicine, Research & Experimental
Maria Russi, Gabriele Cavalieri, Domenico Marson, Erik Laurini, Sabrina Pricl
Summary: This study investigates the binding mechanism of two B-Raf tyrosine kinase inhibitors, dabrafenib and vemurafenib, to human serum albumin (HSA). The results show that both drugs bind spontaneously and with a 1:1 stoichiometry to the same binding pocket on HSA, without significantly affecting the protein's secondary structure. However, the nature of the drug-protein interactions differs, with dabrafenib being more entropically driven and vemurafenib being mainly enthalpic. Kinetic analysis reveals similar association rates for both drugs, but vemurafenib has a slightly longer residence time within the HSA binding pocket.
MOLECULAR PHARMACEUTICS
(2022)
Article
Biochemical Research Methods
Mattia Spano, Stephane Andreani, Jean-Valere Naubron, Luisa Mannina, Sabrina Pricl, Alain Muselli, Aura Tintaru
Summary: Unambiguous identification of components in natural mixtures is a challenging and meticulous task. Traditional methods often fail to address delicate and equivocal issues. This paper proposes an original methodology based on ion mobility mass spectrometry for the analysis of natural samples, and demonstrates its effectiveness through a case study.
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Michele Tonelli, Marco Catto, Raimon Sabate, Valeria Francesconi, Erik Laurini, Sabrina Pricl, Leonardo Pisani, Daniela Valeria Miniero, Grazia Maria Liuzzi, Elena Gatta, Annalisa Relini, Rosalina Gavin, Jose Antonio Del Rio, Fabio Sparatore, Angelo Carotti
Summary: A set of thioxanthene-9-one and xanthene-9-one derivatives were evaluated for their inhibition of tau protein aggregation. Compound 20 showed outstanding biological data with inhibitory potency against tau protein and A beta 40 aggregation, and also exhibited neuroprotective activity. Compound 10 demonstrated good inhibition of cholinesterases with low cytotoxicity. Compound 4 showed high potency as a butyrylcholinesterase inhibitor with selectivity against acetylcholinesterase. These findings suggest that thioxanthene-9-one derivatives have the potential for AD therapy, pending further structural variations to improve safety.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Pharmacology & Pharmacy
Maria Russi, Rachele Valeri, Domenico Marson, Chiara Danielli, Fulvia Felluga, Aura Tintaru, Natasa Skoko, Suzana Aulic, Erik Laurini, Sabrina Pricl
Summary: Dabrafenib (DAB) and vemurafenib (VEM), two clinically approved anticancer drugs, were successfully encapsulated into nanomicelles formed by an amphiphilic dendrimer. The nanomicelles demonstrated well-defined structure, high encapsulation efficiency, good drug loading capacity, and pH-dependent drug release. In vitro experiments showed that the drug-loaded nanomicelles exhibited enhanced response compared to free drugs in melanoma cell lines.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Article
Chemistry, Medicinal
Luca Blicker, Rafael Gonzalez-Cano, Erik Laurini, Francisco R. Nieto, Judith Schmidt, Dirk Schepmann, Sabrina Pricl, Bernhard Wunsch
Summary: Antagonists targeting sigma 1 receptors show promise for neuropathic pain treatment. A series of aminodiols were synthesized from (-)-isopulegol (1) and transformed into bicyclic and tricyclic derivatives. The aminodiols exhibited higher sigma 1 affinity compared to the derivatives. The study also revealed the importance of stereochemistry and compound structure in modulating sigma 1 affinity.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Daniel Ferry, Sabrina Pricl, Domenico Marson, Zhongrui Chen, Gabriel Canard, Simon Pascal, Aura Tintaru, Olivier Siri
Summary: In this study, the formation of nanoribbons from N-alkyl azacalixphyrin 4 and nanodonuts from the N-aryl analogue 5 were investigated using molecular dynamics simulations. The different modes of intermolecular interactions were rationalized based on the nature of the N-substituents. Nanoribbons were formed through the stackings of azacalixphyrin cores along the vertical direction, while nanodonuts were self-assembled with macrocyclic cores stacking along the horizontal plane and thorns pointing towards the solvent.
JOURNAL OF PORPHYRINS AND PHTHALOCYANINES
(2023)
Article
Multidisciplinary Sciences
Jiaxuan Chen, Dandan Zhu, Baoping Lian, Kangjie Shi, Peng Chen, Ying Li, Wenyi Lin, Ling Ding, Qiulin Long, Yang Wang, Erik Laurini, Wenjun Lan, Yun Li, Aura Tintaru, Caoyun Ju, Can Zhang, Sabrina Pricl, Juan Iovanna, Xiaoxuan Liu, Ling Peng
Summary: Nucleic acid therapeutics serve as an important drug modality for targeting undruggable targets, responding to evolving pathogens, and precision medicine at the gene level. Dendrimers, as precision delivery systems, have been utilized for selective and on-demand delivery of DNA and siRNA. The properties and performance of these dendrimers were systematically studied, and they exhibited cargo-adaptive and selective delivery, tumor targeting, and redox-responsive cargo release. The dendrimers outperformed currently available vectors in tumor and cancer cell-specific delivery of siRNA and DNA therapeutics in various cancer models. This study provides a pathway for engineering tailor-made vectors for nucleic acid delivery and precision medicine.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Stefano Rosa, Andrea Tagliani, Chiara Bertaso, Luca Tadini, Cristina Visentin, Louise Jane Gourlay, Sabrina Pricl, Lucia Feni, Sara Pellegrino, Paolo Pesaresi, Simona Masiero
Summary: Genetically-encoded combinatorial peptide libraries are useful for identifying peptides with potential therapeutic applications. In this study, a cyclic peptide called G4CP2 was identified and characterized. G4CP2 interferes with the function of GAL4 protein, a transcription factor involved in galactose metabolism in yeast. The results demonstrate the potential biotechnological applications of G4CP2 and the utility of CYCLIC as a tool for peptide identification.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Article
Pharmacology & Pharmacy
Gabriele Cavalieri, Giulia Cilurzo, Lorenzo Pettorosso, Andrea Mansueto, Erik Laurini, Sabrina Pricl
Summary: The combination therapy of BRAF and MEK inhibitors shows better outcomes in melanoma treatment than monotherapy. Encorafenib and Binimetinib have been identified as an effective treatment modality. The comprehensive approach of fluorescence spectroscopy, isothermal titration calorimetry, far-UV circular dichroism, and molecular simulations reveals the binding mechanisms and stability of the inhibitors with human serum albumin.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Review
Pharmacology & Pharmacy
Sabrina Pricl
Summary: COST Action CA17140 is an interdisciplinary network aiming to promote research and development in cancer nanomedicine. This action provides a timely instrument to rationalize and focus research efforts at the European level in translating nanomedicine in cancer. Within this action, dendrimers play a vital role in oncology.
Article
Chemistry, Medicinal
Luca Blicker, Rafael Gonzalez-Cano, Erik Laurini, Francisco R. Nieto, Judith Schmidt, Dirk Schepmann, Sabrina Pricl, Bernhard Wuensch
Summary: Antagonists at a1 receptors have great potential for treating neuropathic pain. The study examined different compounds and found that amino-diols showed higher a1 affinity than bicyclic and tricyclic derivatives. The configuration and structure of the compounds also influenced their a1 affinity and selectivity. A specific compound, aminodiol 8b, demonstrated high a1 affinity, selectivity, and promising activity in pain relief.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Dinesh Dhumal, Bar Maron, Einav Malach, Zhenbin Lyu, Ling Ding, Domenico Marson, Erik Laurini, Aura Tintaru, Brigino Ralahy, Suzanne Giorgio, Sabrina Pricl, Zvi Hayouka, Ling Peng
Summary: The urgent need for innovative antibacterial agents due to the antibiotic resistance crisis is addressed in this study. The researchers developed antibacterial candidates based on self-assembled supramolecular dendrimer nanosystems, which exhibited strong antibacterial activity and prevented biofilm formation.
