Review
Pharmacology & Pharmacy
Wenxiao Jiang, Guiqing Cai, Peter Hu, Yue Wang
Summary: Non-small cell lung cancer is recognized as one of the deadliest cancers globally, driven by smoking and air pollution. With the advancement of personalized medicine, physicians are increasingly aware of how to more effectively use anti-cancer agents.
ACTA PHARMACEUTICA SINICA B
(2021)
Article
Biochemistry & Molecular Biology
Jeevitha Priya Manoharan, Kavinkumar Nirmala Karunakaran, Subramanian Vidyalakshmi, Karthik Dhananjayan
Summary: This study investigates the effects of selective Annonaceous acetogenins (AAs) on the B1 subtype of ABC transporter using computational simulations. The results show that Annonacin A has a higher binding affinity with ABCB1 and could potentially serve as a drug lead in reversing multi-drug resistance in tumor cells.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Chemistry, Medicinal
David S. P. Cardoso, Nikoletta Szemeredi, Gabriella Spengler, Silva Mulhovo, Daniel J. V. A. dos Santos, Maria-Jose U. Ferreira
Summary: The study reported a monoterpene indole alkaloid Dregamine isolated from Tabernaemontana elegans, which underwent chemical transformations to produce azines and semicarbazones with various substituents. These derivatives exhibited potent multidrug resistance (MDR) reversal activity, especially those containing aromatic substituents in the azine moieties.
Article
Environmental Sciences
Tushar Khare, Sneha Mahalunkar, Varsha Shriram, Suresh Gosavi, Vinay Kumar
Summary: The global rise in antibiotic resistance among bacterial populations poses a serious threat to human health, requiring novel therapeutic approaches. By assessing the synergistic potential of synthesized nanoparticles with antibiotics, the minimum inhibitory concentration of multidrug resistant bacteria was successfully reduced.
ENVIRONMENTAL RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Mahmoud A. A. Ibrahim, Khlood A. A. Abdeljawaad, Laila A. Jaragh-Alhadad, Hesham Farouk Oraby, Mohamed A. M. Atia, Othman R. Alzahrani, Gamal A. H. Mekhemer, Mahmoud F. Moustafa, Ahmed M. Shawky, Peter A. Sidhom, Alaa H. M. Abdelrahman
Summary: The development of multidrug resistance (MDR) caused by overexpression of P-glycoprotein (P-gp/ABCB1/MDR1) is the main reason for the failure of chemotherapy in carcinoma treatment. An in silico study was conducted to discover potential P-gp inhibitors by assessing the binding energies of 512 drug candidates. Five promising drug candidates, valspodar, dactinomycin, elbasvir, temsirolimus, and sirolimus, showed strong binding energies against P-gp transporter and displayed good pharmacokinetic properties. These results indicate their potential as prospective P-gp inhibitors and require further in vitro/in vivo investigations.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Microbiology
Carlos Sabater, Natalia Molinero, Manuel Ferrer, Carmen Maria Garcia Bernardo, Susana Delgado, Abelardo Margolles
Summary: This study characterized three gallbladder metagenomes and a fosmid library, focusing on the metagenomic dark matter fraction. Several protein functional domains were annotated in the dark matter fraction, along with the discovery of a novel deacetylase enzyme. Computational pipelines used in this study can help in discovering novel microbial enzymes with previously uncharacterized functions.
Article
Biochemistry & Molecular Biology
Mahmoud A. A. Ibrahim, Khlood A. A. Abdeljawaad, Alaa H. M. Abdelrahman, Laila A. Jaragh-Alhadad, Hesham Farouk Oraby, Eslam B. Elkaeed, Gamal A. H. Mekhemer, Gamal A. Gabr, Ahmed M. Shawky, Peter A. Sidhom, Mahmoud E. S. Soliman, Mahmoud F. Moustafa, Paul W. Pare, Mohamed-Elamir F. Hegazy
Summary: In this study, potential anticancer drugs that can inhibit ABCB1 transporter were identified using the NPASS database. The stability and binding affinity of five compounds were validated through molecular dynamics simulations. The results suggest that these compounds hold promise as ABCB1 drug candidates and should be further tested in vitro/in vivo.
Article
Biochemistry & Molecular Biology
Kumari Shalini, Shikha Guleria, Deeksha Salaria, Rajan Rolta, Olatomide A. Fadare, Jyoti Mehta, Oladoja Awofisayo, Parteek Mandyal, Pooja Shandilya, Neha Kaushik, Eun Ha Choi, Shikha Rangra Chandel, Nagendra Kumar Kaushik
Summary: This research investigated the interactions between the medicinal plant Acorus calamus and bacterial and fungal protein targets. Among the major phytoconstituents, beta-cadinene showed the best binding interaction with the protein targets, following all rules of drug likeness and toxicity. Molecular docking and MD simulation studies demonstrated the stability of beta-cadinene in the binding pocket of the protein targets. Based on these findings, beta-cadinene can be considered as a potential treatment for bacterial and fungal infections, but further in vitro and in vivo validation is required.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Srijeyagowri Murugaiyaa Pandiyan, Priyadharshini Shanmugaraj, Jeevitha Priya Manoharan, Subramanian Vidyalakshmi
Summary: The study identified four lead acetogenins (AGEs) as potential competitive inhibitors for multidrug resistance (MDR) in colorectal cancer (CRC). Network pharmacological studies established the correlative CRC targets and their mechanisms of action. Further experimental studies are necessary to validate these findings.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Plant Sciences
Michel-Gael F. Kuete, Naomie D. M. Messina, Armelle T. Mbaveng, Paul Nayim, Jenifer Reine N. Kuete, Valaire Y. Matieta, Godloves F. Chi, Bonaventure T. Ngadjui, Victor Kuete
Summary: The stem bark extract of Enantia chlorantha possesses significant antibacterial activity against multidrug-resistant bacteria, with compound 1 showing the best antibacterial effects. Compounds 1-3 were found to potentiate the antibacterial activity of antibiotics such as norfloxacin, ciprofloxacin, and doxycycline against multidrug-resistant bacteria.
JOURNAL OF ETHNOPHARMACOLOGY
(2022)
Article
Oncology
Lingjian Guo, Haixia Shi, Limin Zhu
Summary: This study aimed to elucidate the mechanism of Siteng Fang (STF) in reversing multidrug resistance (MDR) in gastric cancer (GC), identifying key active ingredients, core targets, and signaling pathways associated with MDR. Molecular docking results showed that the core active ingredients, quercetin and diosgenin, bind well to their targets. Findings suggest that STF may reverse MDR in GC mainly through the action on the PI3K/AKT signaling pathway.
FRONTIERS IN ONCOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Perez-De Marcos Juan-Carlos, Perez-Pineda Perla-Lidia, Mendez-Morales Stephanie-Talia, Arellano-Mendoza Monica-Griselda, Torres-Espindola Luz-Maria
Summary: The ATP binding-cassette superfamily, mostly transmembrane transporters found in humans, plays a key role in regulating various physiological functions and is associated with multidrug resistance and pharmacological response regulation.
MOLECULAR BIOLOGY REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Julia Schaefer, Vincent Julius Kloesgen, Ejlal A. Omer, Onat Kadioglu, Armelle T. Mbaveng, Victor Kuete, Andreas Hildebrandt, Thomas Efferth
Summary: Cancer therapy is often hindered by drug resistance and severe side effects. Phytochemicals are a valuable resource for developing less toxic drugs. Bioinformatics can simplify the drug development process. This study analyzed 375 phytochemicals and identified six compounds with potential anticancer activity and P-gp inhibition.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Mahmoud A. A. Ibrahim, Alaa H. M. Abdelrahman, Esraa A. A. Badr, Nahlah Makki Almansour, Othman R. Alzahrani, Muhammad Naeem Ahmed, Mahmoud E. S. Soliman, Mohamed Ahmed Naeem, Ahmed M. Shawky, Peter A. Sidhom, Gamal A. H. Mekhemer, Mohamed A. M. Atia
Summary: In this study, the potential ABCG2 inhibitors NPACT00968 and NPACT01545 were identified through computational screening. Molecular dynamics simulations showed that these two compounds exhibited stable binding to ABCG2 transporter. The results suggest that further experimental investigations are warranted.
MOLECULAR DIVERSITY
(2022)
Article
Biochemistry & Molecular Biology
Muhammad Yasir, Jinyoung Park, Eun-Taek Han, Won Sun Park, Jin-Hee Han, Yong-Soo Kwon, Hee-Jae Lee, Mubashir Hassan, Andrzej Kloczkowski, Wanjoo Chun
Summary: In this study, a three-dimensional structure of DAX1 was modeled, and network analysis and molecular docking were conducted to evaluate the association of DAX1 with Ewing Sarcoma. Flavonoid compounds were found to interact with the active region of DAX1 and could potentially be used as therapeutic agents against DAX1-mediated augmentation of ES.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Pharmacology & Pharmacy
B. Siva Lokesh, Prakash Haloi, V. Badireenath Konkimalla
Summary: In this study, PEITC-loaded biocompatible nanoparticles were successfully developed using BSA and PEG as biodegradable polymers. The optimized nanoparticles exhibited smaller particle size, good stability, higher drug encapsulation efficiency and drug loading. The nanoparticles showed sustained release of PEITC and demonstrated enhanced antibacterial activity compared to free PEITC. In a mice infection model, PEITC nanoparticles significantly reduced the area of infection and bacterial viability.
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Eman H. Reda, Nesrine M. Hegazi, Mona Marzouk, Zienab T. Abdel Shakour, Ali M. El-Halawany, El-Sayeda A. El-Kashoury, Tarik A. Mohamed, Mahmoud A. A. Ibrahim, Khaled A. Shams, Nahla S. Abdel-Azim, Christopher J. Kampf, Thomas Efferth, Paul. W. Pare, Mohamed-Elamir F. Hegazy
Summary: LC-MS/MS analysis was used to investigate the metabolome of Centaurea lipii and identified cinnamic acids, sesquiterpene lactones, flavonoids, and lignans as the major chemical classes. Bioassay-guided fractionation confirmed that sesquiterpene lactones were responsible for the cytotoxic activity.
Article
Biochemistry & Molecular Biology
Ejlal A. Omer, Sara Abdelfatah, Max Riedl, Christian Meesters, Andreas Hildebrandt, Thomas Efferth
Summary: During the past three decades, humans have faced different coronavirus outbreaks, including the recent COVID-19 pandemic. In this study, researchers targeted a protein called nsp16, which is present in multiple coronavirus strains, to develop inhibitors. Using computational methods, they identified nine compounds with strong binding to nsp16 in SARS-CoV-2, SARS-CoV-1, and MERS-CoV. Further experiments confirmed the effectiveness of these compounds and their potential as therapeutic agents. Overall, three novel inhibitors were discovered, showing broad-spectrum activity against multiple coronavirus strains.
Article
Nanoscience & Nanotechnology
Shounak Roy, Prakash Haloi, Rajat Choudhary, Saurabh Chawla, Monika Kumari, V. Badireenath Konkimalla, Amit Jaiswal
Summary: The rapid emergence of multidrug-resistant bacterial strains poses a global threat to public health. Hospital-acquired infections in diabetic and burn patients impede wound healing and result in high mortality. Researchers have developed a new biomaterial, MCP glycosheets, that synergistically destroys pathogenic strains and promotes wound healing. These glycosheets efficiently eradicate both Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus within a short period of time, leading to rapid and highly efficient in vivo wound disinfection and healing.
ACS APPLIED MATERIALS & INTERFACES
(2023)
Article
Oncology
Eva-Maria Hartinger, Anne Mahringer, Soumitra Kumar Choudhuri, Gert Fricker, Thomas Efferth
Summary: Copper N-(2hydroxy acetophenone) glycinate (CuNG) has shown anticancer activity and modulates drug resistance. This study investigated the modulatory effects of CuNG on four ABC transporters (MRP1, MRP1, BCRP, and P-glycoprotein). Results showed that CuNG increased sensitivity to doxorubicin and efflux activity in cells over-expressing MRP1 and hBCRP, but increased resistance and decreased efflux activity in Caco-2 cells.
ANTICANCER RESEARCH
(2023)
Article
Chemistry, Medicinal
Jun Li, Nasir Tajuddeen, Doris Feineis, Virima Mudogo, Marcel Kaiser, Ean-Jeong Seo, Thomas Efferth, Gerhard Bringmann
Summary: A new dimeric naphthylisoquinoline alkaloid, jozibrevine D (4e), was isolated from the liana Ancistrocladus ileboensis in Central Africa. It has potent antiprotozoal activity against P. falciparum and exhibits good cytotoxic activities against acute lymphoblastic leukemia cells and their multidrug-resistant subline. The absolute stereostructure of the new compound was determined using various methods including NMR, oxidative degradation, and electronic circular dichroism (ECD) spectroscopy.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Cell Biology
Min Zhou, Joelle C. Boulos, Sabine M. Klauck, Thomas Efferth
Summary: This study investigates the cytotoxicity and molecular mode of action of the synthetic cardenolide ZINC253504760 on multidrug-resistant cancer cells. The results show that ZINC253504760 induces cell death and inhibits cell proliferation through the induction of parthanatos and inhibition of MEK phosphorylation.
CELL BIOLOGY AND TOXICOLOGY
(2023)
Article
Pharmacology & Pharmacy
Prakash Haloi, B. Siva Lokesh, Saurabh Chawla, V. Badireenath Konkimalla
Summary: A study reported a method to treat rheumatoid arthritis (RA) by co-delivering methotrexate (MTX) and phenethyl isothiocyanate (PEITC) using a sodium alginate-pluronic F127 in situ hydrogel formulation. The co-delivery of MTX and PEITC in nanoparticulate form enhanced stability and solubility, and facilitated greater penetration into arthritic tissues. The method significantly reduced chronic inflammation, delayed bone erosion, and improved joint morphology in RA rats.
Article
Pharmacology & Pharmacy
Yuan-Qing Qu, Lin-Lin Song, Su-Wei Xu, Margaret Sum Yee Yu, Onat Kadioglu, Francesco Michelangeli, Betty Yuen Kwan Law, Thomas Efferth, Christopher Wai- Kei Lam, Vincent Kam Wai Wong
Summary: In this study, pomiferin, a natural product from Osage Orange, was found to activate autophagy and inhibit drug efflux to overcome innate and acquired drug resistance in cancer cells. It also exhibited tumor suppression and anti-metastatic effects in animal models. Pomiferin could serve as a novel effective agent for circumventing drug resistance in clinical applications.
PHARMACOLOGICAL RESEARCH
(2023)
Article
Plant Sciences
Yue Jia, Juzhao Liu, Qin Yang, Wanjiang Zhang, Thomas Efferth, Siguo Liu, Xin Hua
Summary: A natural compound called cajanin stilbene acid (CSA) has been found to effectively restore the sensitivity of polymyxin B to MCR-1 positive Escherichia coli (E. coli). CSA can bind to the key amino acids of the MCR-1 protein, inhibiting its enzymatic activity and thus restoring the sensitivity of polymyxin B.
Article
Plant Sciences
Zhiwei Xu, Xiaojie Zhou, Xiao Hong, Sichen Wang, Jiale Wei, Junhao Huang, Liting Ji, Yuanxiao Yang, Thomas Efferth, Chunlan Hong, Changyu Li
Summary: In this study, it was found that Shi chang pu (SCP-oil) can improve cognitive impairment, reduce pathological damage, and inhibit neuroinflammation in AD mice. This neuroprotective effect is achieved through the inhibition of the NF-kappa B signaling pathway and reduced activation of the NLRP3 inflammasome.
Article
Nanoscience & Nanotechnology
Prem Singh, Prakash Haloi, Khushal Singh, Shounak Roy, Ankita Sarkar, B. Siva Lokesh, Rajat Choudhary, Chandrasen Mohite, Saurabh Chawla, V. Badireenath Konkimalla, Pallab Sanpui, Amit Jaiswal
Summary: Recent developments in nanomaterials have led to the application of plasmonic photothermal therapy (PPTT) for the treatment of cancer. However, the limitations of low penetration depth of NIR-I lights and high laser power density have restricted its clinical translation. To overcome these shortcomings, the researchers have developed a bimetallic palladium nanocapsule (Pd Ncap) that can be used for PPTT in both NIR-I and NIR-II regions. The Pd Ncap exhibits excellent photothermal stability and killing efficiency, with the potential to protect cells from reactive oxygen species (ROS) produced during PPTT.
ACS APPLIED MATERIALS & INTERFACES
(2023)
Review
Biology
Janani Manochkumar, Aswani Kumar Cherukuri, Raju Suresh Kumar, Abdulrahman I. Almansour, Siva Ramamoorthy, Thomas Efferth
Summary: This review provides a comprehensive overview of the -omics and multi-omics approaches used for characterizing marine metabolites, along with the need for data integration and machine learning algorithms. It also discusses the challenges and recommendations for conducting multi-omics studies.
COMPUTERS IN BIOLOGY AND MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Matteo Rosellini, Alicia Schulze, Ejlal A. Omer, Nadeen T. Ali, Federico Marini, Jan-Heiner Kuepper, Thomas Efferth
Summary: In recent years, plastic and microplastic in the oceans have caused problems to marine flora and fauna, and have also been found in human blood and milk, suggesting their ability to enter the human body. This study examined the interactions between plastic-related compounds and the cytochrome CYP2C19, and identified candidates that can interact with this protein. These compounds exhibited cytotoxic activity and affected various metabolic pathways, suggesting a potential for liver damage.
Review
Plant Sciences
Ressin Varghese, Thomas Efferth, Siva Ramamoorthy
Summary: Lung cancer, a leading malignancy worldwide, has been mitigated through the use of phytopigments such as carotenoids. While in vitro and animal studies have shown promising results, clinical trials have yielded contradictory outcomes, highlighting the need for further verification.
Article
Pharmacology & Pharmacy
Paola Orlandi, Marta Banchi, Francesca Vaglini, Marco Carli, Stefano Aringhieri, Arianna Bandini, Carla Pardini, Cristina Viaggi, Michele Lai, Greta Ali, Alessandra Ottani, Eleonora Vandini, Patrizia Guidi, Margherita Bernardeschi, Veronica La Rocca, Giulio Francia, Gabriella Fontanini, Mauro Pistello, Giada Frenzilli, Daniela Giuliani, Marco Scarselli, Guido Bocci
Summary: This study investigates the role of MC4R in melanoma and the use of the selective antagonist ML in combination with vemurafenib. The results show that ML can inhibit melanoma cell proliferation and induce apoptosis through the inhibition of ERK1/2 phosphorylation and reduction of BCL-XL expression. The combination of vemurafenib and ML exhibits a synergistic effect in vitro and inhibits tumor growth in vivo without causing adverse effects.
BIOCHEMICAL PHARMACOLOGY
(2024)
Article
Pharmacology & Pharmacy
Conor J. Bloxham, Katina D. Hulme, Fabrizio Fierro, Christian Fercher, Cassandra L. Pegg, Shannon L. O'Brien, Simon R. Foster, Kirsty R. Short, Sebastian G. B. Furness, Melissa E. Reichelt, Masha Y. Niv, Walter G. Thomas
Summary: Bitter taste receptors (T2Rs) are a type of G protein-coupled receptors that allow humans to detect aversive and toxic substances. This study characterized the functional properties of previously identified T2Rs in human cardiac tissues and their naturally occurring polymorphisms. The results showed differences in signaling among different T2R variants, and revealed a potential association between the T2R50 Tyr203 variant and cardiovascular disease.
BIOCHEMICAL PHARMACOLOGY
(2024)
Article
Pharmacology & Pharmacy
Lu Chen, Huanying Shi, Wenxin Zhang, Yongjun Zhu, Haifei Chen, Zimei Wu, Huijie Qi, Jiafeng Liu, Mingkang Zhong, Xiaojin Shi, Tianxiao Wang, Qunyi Li
Summary: This study demonstrates that Carfilzomib exhibits potent anti-tumor activity against esophageal squamous cell carcinoma (ESCC) by triggering mitochondrial apoptosis and reprogramming cellular metabolism. It has been identified that activating transcription factor 3 (ATF3) plays a crucial role as a cellular target in ESCC cells treated with Carfilzomib. Overexpression of ATF3 effectively counteracts the effects of Carfilzomib on ESCC cell proliferation, apoptosis, and metabolic reprogramming. Furthermore, ATF3 mediates the anti-tumor activity of Carfilzomib, suggesting its potential as a therapeutic agent for ESCC.
BIOCHEMICAL PHARMACOLOGY
(2024)
Review
Pharmacology & Pharmacy
Xing Zhang, Xiang Li, Ran Xia, Hong-Sheng Zhang
Summary: This review summarizes recent progress on the mechanisms of ferroptosis resistance in cancer and highlights the role of redox status and metabolism. Combination therapy for ferroptosis has great potential in treating resistant malignant tumors.
BIOCHEMICAL PHARMACOLOGY
(2024)