Article
Biochemistry & Molecular Biology
Shafi Mahmud, Md. Jahirul Islam, Md. Rimon Parves, Md. Arif Khan, Lamiya Tabussum, Sinthyia Ahmed, Md. Ackas Ali, Sayo O. Fakayode, Mohammad A. Halim
Summary: This study aimed to identify potent inhibitors of P-glycoprotein using computational approaches. Two compounds showed promising anti-tumor activity with acceptable pharmacokinetic properties, and molecular docking and dynamics simulations verified their stable binding with P-glycoprotein. Principal component analysis and QSAR modeling provided insights into the interactions and predictive capabilities of the drug candidates.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Biochemistry & Molecular Biology
Jason W. Y. Kan, Clare S. W. Yan, Iris L. K. Wong, Xiaochun Su, Zhen Liu, Tak Hang Chan, Larry M. C. Chow
Summary: Biotransformation of flavonoid dimer FD18 resulted in an active metabolite FM04, which exhibited improved druggability and was more potent in reversing P-gp-mediated PTX resistance. FM04 sensitized cancer cells to multiple anticancer drugs by inhibiting P-gp transport activity and stimulating P-gp ATPase. In addition, FM04 enhanced the intestinal absorption of PTX and showed significant antitumor activity in mouse models.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Medicinal
Laura Braconi, Silvia Dei, Marialessandra Contino, Chiara Riganti, Gianluca Bartolucci, Dina Manetti, Maria Novella Romanelli, Maria Grazia Perrone, Nicola Antonio Colabufo, Stefano Guglielmo, Elisabetta Teodori
Summary: New 2,5- and 1,5-disubstituted tetrazoles, and 2,5-disubstituted-1,3,4-oxadiazoles were synthesized and studied as MDR reversers, showing potent inhibitory effects on P-gp transport activity and increasing the antiproliferative effect of doxorubicin in MDR cells.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
David S. P. Cardoso, Annamaria Kincses, Marta Nove, Gabriella Spengler, Silva Mulhovo, Joao Aires-de-Sousa, Daniel J. V. A. dos Santos, Maria-Jose U. Ferreira
Summary: This study aimed to enhance multidrug resistance (MDR) reversing activity in cancer by deriving new compounds from major epimeric alkaloids isolated from Tabernaemontana elegans. The derivatives showed increased activity, with those containing N-phenethyl moieties exhibiting the strongest P-glycoprotein inhibitory effects. Synergistic interactions with the antineoplastic drug doxorubicin were observed, highlighting the potential of these compounds as MDR reversers. Lipophilicity and bulkiness features were associated with inhibitory activity based on the explored QSAR models.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Wenqin Sun, Iris L. K. Wong, Helen Ka-Wai Law, Xiaochun Su, Terry C. F. Chan, Gege Sun, Xinqing Yang, Xingkai Wang, Tak Hang Chan, Shengbiao Wan, Larry M. C. Chow
Summary: Tea polyphenol derivative EC31 is a potent and nontoxic P-gp inhibitor that can reverse multidrug resistance and enhance the efficacy of anticancer drugs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Physical
Linna Liang, Wendi Huo, Bei Wang, Lingzhi Cao, Haoran Huo, Yixin Liu, Yi Jin, Xinjian Yang
Summary: Tumor multidrug resistance is a major cause of chemotherapy failure, and reversing tumor multidrug resistance is crucial for increasing the sensitivity of tumor cells to chemodrugs. The self-assembled DNAzyme nanoflowers can efficiently reverse multidrug resistance, enhance drug loading capacity, and suppress P-glycoprotein expression.
JOURNAL OF COLLOID AND INTERFACE SCIENCE
(2022)
Review
Pharmacology & Pharmacy
Sachin Rathod, Heta Desai, Rahul Patil, Jayant Sarolia
Summary: This article discusses the significance of studying P-glycoprotein in drug delivery and highlights the effective reversal of P-gp inhibition using nonionic surfactants. Nonionic surfactants, being inert, non-toxic, and efficient, show potential as P-gp inhibitors and improve drug absorption and bioavailability through various mechanisms.
Article
Pharmacology & Pharmacy
Sofija Jovanovic Stojanov, Epole N. Ntungwe, Jelena Dinic, Ana Podolski-Renic, Milica Pajovic, Patricia Rijo, Milica Pesic
Summary: Coleon U, a natural compound not recognized as a substrate of P-glycoprotein, has equal efficacy against sensitive and multidrug-resistant cancer cells. It delays the decrease in P-glycoprotein activity by decreasing mitochondrial membrane potential and inhibiting P-glycoprotein expression.
Retraction
Oncology
S. Mohana, M. Ganesan, N. Rajendra Prasad, D. Ananthakrishnan, D. Velmurugan
Summary: A correction to this paper has been published and is accessible through the original article.
Article
Chemistry, Medicinal
Ayitila Maimaitijiang, Bianlin Wang, Hequn Yang, Dan Tang, Yongqiang Liu, Haji Akber Aisa
Summary: In this study, the researchers investigated the effects of jatrophane derivatives on multidrug resistance in cancer chemotherapy. They found that compound 17 showed potent reversal activity and low cytotoxicity, and increased the intracellular accumulation of the drug. These findings provide a promising candidate for reversing multidrug resistance.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Manuela Labbozzetta, Paola Poma, Monica Notarbartolo
Summary: Acute myeloid leukemia (AML) is difficult to treat due to the development of resistance to both traditional chemotherapy and new drugs in some patients. Multidrug resistance (MDR) in AML is often caused by the overexpression of P-glycoprotein (P-gp), which is an efflux pump. This mini-review focuses on the advantages of using natural substances as inhibitors of P-gp, including phytol, curcumin, lupeol, and heptacosane, and their mechanisms of action in AML.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Yasmeen Cheema, Yusra Sajid Kiani, Kenneth J. J. Linton, Ishrat Jabeen
Summary: Researchers developed a pharmacophore model based on the cryo-EM structure of ABCB1 to screen for new inhibitors, resulting in the identification of six potential inhibitors with distinct chemistries and favorable properties. The compounds exhibited low nanomolar range inhibitory concentrations and two of them were able to resensitize ABCB1-expressing cells to taxol. This study demonstrates the utility of cryo-electron microscopy in drug identification and design.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Agronomy
Tan Dai, Zhiwen Wang, Xingkai Cheng, Huige Gao, Li Liang, Pengfei Liu, Xili Liu
Summary: Both fungicide efflux and detoxification metabolism are involved in the resistance mechanisms of Phytophthora capsici to SYP-14288.
PEST MANAGEMENT SCIENCE
(2022)
Article
Pharmacology & Pharmacy
Ko-Hua Yu, Chan-Yen Kuo, I-Ting Wu, Ching-Ho Chi, Keng-Chang Tsai, Ping-Chung Kuo, Jing-Wen Zeng, Chin-Chuan Hung, Hsin-Yi Hung
Summary: Multidrug resistance is a significant challenge in cancer chemotherapy, but arctigenin derivatives show potential in reversing this resistance, especially when combined with paclitaxel.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Review
Oncology
Yichen Tian, Yongrong Lei, Yani Wang, Jiejuan Lai, Jianhua Wang, Feng Xia
Summary: This review summarizes the mechanisms of multidrug resistance (MDR) mediated by P-glycoprotein (P-gp), including the regulation of efflux activity, the inhibition of P-gp expression, and the knockout of the ABCB1 gene. Inhibiting P-gp through screening and designing suitable compounds and techniques can overcome P-gp-mediated MDR, providing a reference for studying the reversal of P-gp-mediated MDR.
INTERNATIONAL JOURNAL OF ONCOLOGY
(2023)
Article
Oncology
Daniele Campa, Alessandro Martino, Angelica Macauda, Marek Dudzinski, Anna Suska, Agnieszka Druzd-Sitek, Marc-Steffen Raab, Victor Moreno, Stefanie Huhn, Aleksandra Butrym, Juan Sainz, Gergely Szombath, Marcin Rymko, Herlander Marques, Fabienne Lesueur, Annette Juul Vangsted, Ulla Vogel, Marcin Kruszewski, Edyta Subocz, Gabriele Buda, Elzbieta Iskierka-Jazdzewska, Rafael Rios, Maximilian Merz, Ben Schoettker, Grzegorz Mazur, Emeline Perrial, Joaquin Martinez-Lopez, Katja Butterbach, Ramon Garcia Sanz, Hartmut Goldschmidt, Hermann Brenner, Krzysztof Jamroziak, Rui Manuel Reis, Katalin Kadar, Charles Dumontet, Marzena Watek, Eva Kannik Haastrup, Grzegorz Helbig, Artur Jurczyszyn, Andres Jerez, Judit Varkonyi, Torben Barington, Norbert Grzasko, Jan Maciej Zaucha, Vibeke Andersen, Daria Zawirska, Federico Canzian
LEUKEMIA & LYMPHOMA
(2019)
Article
Biochemical Research Methods
Christian Klein, Wolfgang Schaefer, Joerg T. Regula, Charles Dumontet, Ulrich Brinkmann, Marina Bacac, Pablo Umana
Article
Microbiology
Alexis Moreno, Atanu Banerjee, Rajendra Prasad, Pierre Falson
RESEARCH IN MICROBIOLOGY
(2019)
Article
Biochemistry & Molecular Biology
Atanu Banerjee, Alexis Moreno, Mohammad Firoz Khan, Remya Nair, Suman Sharma, Sobhan Sen, Alok Kumar Mondal, Jorgaq Pata, Cedric Orelle, Pierre Falson, Rajendra Prasad
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2020)
Article
Biochemistry & Molecular Biology
Samer Haidar, Christelle Marminon, Dagmar Aichele, Abdelhamid Nacereddine, Wael Zeinyeh, Abdeslem Bouzina, Malika Berredjem, Laurent Ettouati, Zouhair Bouaziz, Marc Le Borgne, Joachim Jose
Article
Biochemistry & Molecular Biology
Szilard Toth, Aron Szepesi, Viet-Khoa Tran-Nguyen, Balazs Sarkadi, Katalin Nemet, Pierre Falson, Attilio Di Pietro, Gergely Szakacs, Ahcene Boumendjel
Article
Multidisciplinary Sciences
Rachad Nasr, Doriane Lorendeau, Ruttiros Khonkarn, Lauriane Dury, Basile Peres, Ahcene Boumendjel, Jean-Claude Cortay, Pierre Falson, Vincent Chaptal, Helene Baubichon-Cortay
SCIENTIFIC REPORTS
(2020)
Article
Chemistry, Medicinal
Emile Roussel, Alexis Moreno, Nicolas Altounian, Christian Philouze, Basile Peres, Aline Thomas, Olivier Renaudet, Pierre Falson, Ahcene Boumendjel
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2020)
Review
Microbiology
Atanu Banerjee, Jorgaq Pata, Suman Sharma, Brian C. Monk, Pierre Falson, Rajendra Prasad
Summary: Multidrug resistance transporters play a major role in clinical drug resistance in fungi, able to extrude a wide range of structurally unrelated molecules at rates that prevent lethal effects. The drug transporters CaCdr1 and CaMdr1 in Candida albicans utilize a strategy of promiscuity to actively export antifungal drugs, as shown through intense genetic analysis. Studies have provided insight into how these multidrug transporters function and deliver their remarkable polyspecificity.
Article
Chemistry, Medicinal
Nathalie Guragossian, Billel Belhani, Alexis Moreno, Magda Teixeira Nunes, Lucia Gonzalez-Lobato, Christelle Marminon, Laurent Berthier, Amanda Do Rocio Andrade Pires, Csilla Ozvegy-Laczka, Balazs Sarkadi, Raphael Terreux, Zouhair Bouaziz, Malika Berredjem, Joachim Jose, Attilio Di Pietro, Pierre Falson, Marc Le Borgne
Summary: New dimeric inhibitors targeting BCRP/ABCG2 were designed with high potency and therapeutic ratio, showing specificity in inhibiting drug efflux. The study suggests that the non-competitive mechanism by which substrate promotes inhibitor binding may be useful for targeting anticancer drug efflux.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Robin Birus, Ehab El-Awaad, Laurens Ballentin, Faten Alchab, Dagmar Aichele, Laurent Ettouati, Claudia Goetz, Marc Le Borgne, Joachim Jose
Summary: The study found that compounds 5a-2 and CX-4945 have similar effects on CK2 activity in vitro, but significant differences in their effects on cancer cells were observed through live-cell imaging. While 5a-2 was more effective in inhibiting tumor cell migration, CX-4945 showed a stronger pro-apoptotic effect on tumor cells. The subcellular distribution of the compounds, with CX-4945 being localized more in the nucleus and 5a-2 detectable mostly in the cytoplasm, may explain the different cellular effects observed.
Article
Multidisciplinary Sciences
Vincent Chaptal, Veronica Zampieri, Benjamin Wiseman, Cedric Orelle, Juliette Martin, Kim-Anh Nguyen, Alexia Gobet, Margot Di Cesare, Sandrine Magnard, Waqas Javed, Jad Eid, Arnaud Kilburg, Marine Peuchmaur, Julien Marcoux, Luca Monticelli, Martin Hogbom, Guy Schoehn, Jean-Michel Jault, Ahcene Boumendjel, Pierre Falson
Summary: This study resolved three outward-facing conformations of BmrA, a multidrug ABC transporter, using x-ray crystallography and cryo-electron microscopy. It was found that two R6G molecules bind to the drug-binding cavity, inducing a rearrangement of TM1-2 and highlighting local flexibility. Simulations showed that in the absence of R6G, the cavity quickly closed after drug release, while in the presence of R6G, the cavity remained open.
Article
Microbiology
Suman Sharma, Atanu Banerjee, Alexis Moreno, Archana Kumari Redhu, Pierre Falson, Rajendra Prasad
Summary: In this study, researchers identified five strains that recovered drug-resistance capacity by expressing CaMdr1 with a secondary mutation, highlighting a mechanistic role and interplay thought to be conserved among MFS proteins. Most of these mutants belong to different signature motifs, pointing to a specific role of TMH11 in the interplay between the N- and C-domains.
Article
Chemistry, Multidisciplinary
Simon Megy, Stephanie Aguero, David Da Costa, Myriam Lamrayah, Morgane Berthet, Charlotte Primard, Bernard Verrier, Raphael Terreux
Article
Materials Science, Biomaterials
Joelle Balegamire, Marc Vandamme, Emmanuel Chereul, Salim Si-Mohamed, Samira Azzouz Maache, Eyad Almouazen, Laurent Ettouati, Hatem Fessi, Loic Boussel, Philippe Douek, Yves Chevalier
BIOMATERIALS SCIENCE
(2020)