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
Chemistry, Multidisciplinary
Lara Garcia-Varela, Pascalle Mossel, Pablo Aguiar, Daniel A. Vazquez-Matias, Aren van Waarde, Antoon T. M. Willemsen, Anna L. Bartels, Nicola A. Colabufo, Rudi A. J. O. Dierckx, Philip H. Elsinga, Gert Luurtsema
Summary: This study found that small changes in P-gp function caused by low doses of tariquidar could be detected by [F-18]MC225-K-1 values, confirming the high sensitivity of the radiotracer.
JOURNAL OF CONTROLLED RELEASE
(2022)
Article
Pharmacology & Pharmacy
Rasmus Blaaholm Nielsen, Rene Holm, Ils Pijpers, Jan Snoeys, Ulla Gro Nielsen, Carsten Uhd Nielsen
Summary: This study aimed to investigate the potential of the combination of the P-gp inhibitor zosuquidar and the nonionic surfactant polysorbate 20 in potentiating P-gp-mediated efflux inhibition. Cell-based experiments and animal experiments revealed that the combination of these two substances can enhance P-gp inhibition in vitro. However, in vivo experiments showed that coadministration of both substances leads to a decrease in oral etoposide bioavailability.
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
Biochemistry & Molecular Biology
Mikael Amaro de Souza, Leilane Gomes Rodrigues, Janaina Esmeraldo Rocha, Thiago Sampaio de Freitas, Paulo Nogueira Bandeira, Marcia Machado Marinho, Matheus Nunes da Rocha, Emmanuel Silva Marinho, Antonio Cesar Honorato Barreto, Henrique Douglas Melo Coutinho, Lorena Mara Alexandre Silva, Murilo Sergio da Silva Juliao, Kirley Marques Canuto, Aluisio Marques da Fonseca, Alexandre Magno Rodrigues Teixeira, Helcio Silva dos Santos
Summary: Chalcones are open chain flavonoid compounds that can be obtained from natural sources or by synthesis and are widely distributed in fruits, vegetables, and tea. They have a simple and easy to handle structure due to the alpha-beta-unsaturated bridge responsible for most biological activities. In this study, the chalcone (E)-1-(4-aminophenyl)-3-(4-nitrophenyl)prop-2-en-1-one (HDZPNB) was characterized by spectroscopy and electronic methods, and its modulating effect on bacterial resistance was investigated.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Chemistry, Medicinal
Reiko Watanabe, Tsuyoshi Esaki, Rikiya Ohashi, Masataka Kuroda, Hitoshi Kawashima, Hiroshi Komura, Yayoi Natsume-Kitatani, Kenji Mizuguchi
Summary: A computer model was developed to predict the efflux potential of drugs through brain capillary endothelial cells' P-gp, proposing a novel system for evaluating brain-to-plasma concentration ratios of P-gp substrates. Validation with experimental data improved the accuracy of predicting drug penetration across the blood-brain barrier, solely based on chemical structure information, compared to previous studies.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Medicine, Research & Experimental
Lara Garcia-Varela, Manuel Rodriguez-Perez, Antia Custodia, Rodrigo Moraga-Amaro, Nicola A. Colabufo, Pablo Aguiar, Tomas Sobrino, Rudi A. J. O. Dierckx, Aren van Waarde, Philip H. Elsinga, Gert Luurtsema
Summary: P-glycoprotein (P-gp) inducer MC111 increases P-gp functionality in the whole brain of rats, potentially offering a treatment option for neurodegenerative diseases.
MOLECULAR PHARMACEUTICS
(2021)
Article
Chemistry, Medicinal
I-Ting Wu, Chan-Yen Kuo, Ching-Hui Su, Yu-Hsuan Lan, Chin-Chuan Hung
Summary: This study investigated the inhibitory effects of pinostrobin and tectochrysin on P-gp in MDR cancer cells and the underlying mechanisms. The results showed that these compounds were not substrates of P-gp and did not affect its expression, but they noncompetitively inhibited the efflux of rhodamine 123 and doxorubicin through P-gp, leading to the resensitization of MDR cancer cells. Therefore, pinostrobin and tectochrysin are effective P-gp inhibitors and potential candidates for resensitizing MDR cancer cells.
Article
Immunology
Jacilene Silva, Janaina Esmeraldo Rocha, Jayze da Cunha Xavier, Thiago Sampaio de Freitas, Henrique Douglas Melo Coutinho, Paulo Nogueira Bandeira, Mateus Rodrigues de Oliveira, Matheus Nunes da Rocha, Emanuelle Machado Marinho, Norberto de Kassio Vieira Monteiro, Lyanna Rodrigues Ribeiro, Ramon Roseo Paula Pessoa Bezerra de Menezes, Marcia Machado Marinho, Alexandre Magno Rodrigues Teixeira, Helcio Silva dos Santos, Emmanuel Silva Marinho
Summary: A large number of infections caused by multi-resistant bacteria result in approximately 700,000 deaths per year worldwide. Chalcones have been studied for their ability to combat microbial resistance to drugs. This research evaluates the antibacterial and antibiotic modifying activity of chalcone (2E)-1-(4'-aminophenyl)-3-(4-methoxyphenyl)-prop-2-en-1-one against Staphylococcus aureus bacteria carrying specific efflux pumps. The results show that chalcone not only has no toxicity on macrophage cells but also synergistically enhances the effects of Norfloxacin and Ethidium Bromide against Staphylococcus aureus. Furthermore, chalcone exhibits favorable physicochemical and pharmacokinetic properties, making it a promising pharmacological active ingredient.
MICROBIAL PATHOGENESIS
(2022)
Article
Biochemistry & Molecular Biology
Catia A. Bonito, Ricardo J. Ferreira, Maria-Jose U. Ferreira, Jean-Pierre Gillet, M. Natalia D. S. Cordeiro, Daniel J. V. A. dos Santos
Summary: In this study, the impact of four P-gp mutations on drug-binding and efflux-related signal-transmission mechanism was evaluated. The repacking of the transmembrane helices induced by mutations and ligands indicates P-gp's sensitivity to perturbations in the transmembrane region. Changes in drug-binding were observed as a consequence of transmembrane helices repacking, but were not always correlated with alterations in ligand binding mode and affinity. The changes in drug efflux are mostly related to changes in drug specificity rather than effects on signal-transmission mechanism.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Shirin Mollazadeh, Farzin Hadizadeh, Ricardo J. Ferreira
Summary: The study found that the stereochemistry of 1,4-dihydropyridines (DHPs) affects their binding ability with P-glycoprotein (P-gp) and can also impact the permeation and accumulation of drugs in cell membranes. Therefore, the stereochemistry should not be overlooked during the development of novel 1,4-dihydropyridine derivatives.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2021)
Article
Chemistry, Medicinal
Martin S. Faillace, Antonio L. Alves Borges Leal, Felipe Araujo de Oliveira Alcantara, Josie H. L. Ferreira, Jose P. de Siqueira-Junior, Carlos E. Sampaio Nogueira, Humberto M. Barreto, Walter J. Pelaez
Summary: Two fluorobenzylidene derivatives showed weak antimicrobial activity against a Staphylococcus aureus strain but significantly enhanced the effectiveness of norfloxacin and ciprofloxacin. The modulation effect of these compounds may involve inhibiting the NorA efflux pump.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Pharmacology & Pharmacy
Paula Hemilia de Souza Nunes, Thiago Sampaio de Freitas, Janaina Esmeraldo Rocha, Raimundo Luiz Silva Pereira, Marcia Machado Marinho, Mateus Rodrigues de Oliveira, Larissa Santos Oliveira, Emanuelle Machado Marinho, Emmanuel Silva Marinho, Silvia Sousa Aquino, Carlos Emidio Sampaio Nogueira, Henrique Douglas Melo Coutinho, Paulo Nogueira Bandeira, Alexandre Magno Rodrigues Teixeira, Helcio Silva dos Santos
Summary: In recent years, bacterial resistance to traditional drugs has increased, making it more important to find new effective antibiotics. This study found that PA-Fluorine enhances antibiotic activity and shows synergistic effects against certain resistant bacterial strains. Molecular docking studies showed that PA-Fluorine interacts with specific efflux pumps. ADMET studies also revealed the potential of PA-Fluorine as an efflux pump inhibitor.
FUNDAMENTAL & CLINICAL PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Dhanamjai Penta, Priya Mondal, Jagadish Natesh, Syed Musthapa Meeran
Summary: The study demonstrates that diindolylmethane can enhance the efficacy of Centchroman in treating breast cancer by modulating drug efflux transporters, inhibiting cell proliferation, inducing apoptosis, and hindering stemness of cancer cells.
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
(2021)
Article
Chemistry, Medicinal
Rinky Raghuvanshi, Sandip B. Bharate
Summary: Kinases are therapeutic targets involved in various diseases. FDA approved kinase inhibitors have shown potential in treating viral infections and possess broad-spectrum antiviral activity.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Chemistry, Medicinal
Deendyal Bhurta, Sandip B. Bharate
Summary: This paper investigates the important role of the styryl group in medicinal chemistry, pointing out the advantages and disadvantages of styryl compounds in drugs, and discusses their impact on biological activity.
Article
Chemistry, Medicinal
Vijay K. Nuthakki, Ramesh Mudududdla, Sandip B. Bharate
Summary: Indoloquinoline (IQ) is an important class of naturally occurring antimalarial alkaloids, with a structural framework consisting of four isomeric ring systems. Aminoalkylation plays a critical role in improving the therapeutic window and biological activity of IQs.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Lingtian Zhang, Marialuisa Moccia, David C. Briggs, Jaideep B. Bharate, Naga Rajiv Lakkaniga, Phillip Knowles, Wei Yan, Phuc Tran, Anupreet Kharbanda, Xiuqi Wang, Yuet-Kin Leung, Brendan Frett, Massimo Santoro, Neil Q. McDonald, Francesca Carlomagno, Hong-yu Li
Summary: This study identified a series of N-trisubstituted pyrimidine derivatives as potential drugs for inhibiting mutant RET kinase. Compound 20 was found to strongly inhibit both RET and RETV804M, and also exhibited anti-proliferative activity against CCDC6-RET-driven LC-2/ad cells.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Chemistry, Medicinal
Deendyal Bhurta, Sandip B. Bharate
Summary: This article critically analyzed the chemical diversity of CDK inhibitors, with amino-pyrimidine being the most represented scaffold. The discussion included selectivity aspects among CDKs, dose-limiting toxicities in clinical trials, and the most advanced clinical candidates. The article also touched on the changing paradigm towards selective inhibitors and provided an overview of ATP-binding pockets of all druggable CDKs.
MEDICINAL RESEARCH REVIEWS
(2022)
Article
Biotechnology & Applied Microbiology
Augustin Ntemafack, Sajad Ahmed, Amit Kumar, Rekha Chouhan, Nitika Kapoor, Sandip B. Bharate, Qazi Parvaiz Hassan, Sumit G. Gandhi
Summary: The research revealed that streptomycetes isolated from Rumex dentatus and BIBP are effective growth-promoting agents that can be utilized as bio-fertilizers in agriculture to enhance the growth and productivity of rice.
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2022)
Article
Multidisciplinary Sciences
Kathleen Shah, Muralidhara Rao Maradana, M. Joaquina Delas, Amina Metidji, Frederike Graelmann, Miriam Llorian, Probir Chakravarty, Ying Li, Mauro Tolaini, Michael Shapiro, Gavin Kelly, Chris Cheshire, Deendyal Bhurta, Sandip B. Bharate, Brigitta Stockinger
Summary: The aryl hydrocarbon receptor (AHR) plays a crucial role in regulating physiological processes in the intestine, influencing tissue regeneration and the acquisition of mature epithelial cell identity after injury.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Medicinal
Ankita Sharma, Vijay K. Nuthakki, Sumeet Gairola, Bikarma Singh, Sandip B. Bharate
Summary: Plants, particularly Nardostachys jatamansi, have been explored for their potential in drug discovery for treating neurodegenerative diseases. This study focused on the phytochemical investigation and semisynthetic modifications of N. jatamansi rhizomes to discover inhibitors for cholinesterase and BACE-1. Several compounds, including 8-acetyl-7-hydroxycoumarin and coumarin-donepezil hybrid, showed promising inhibitory effects on the target enzymes.
Article
Oncology
Lone A. A. Nazir, Naikoo H. H. Shahid, Kumar Amit, Sheikh A. A. Umar, Sharma Rajni, Sandip Bharate, Pyare L. L. Sangwan, Sheikh Abdullah Tasduq
Summary: NPC-402, a derivative of glycyrrhtinic acid, has shown anti-melanoma effects by inducing oxidative stress and apoptosis in melanoma cells. In vivo studies have demonstrated that NPC-402 significantly inhibited angiogenesis and reduced tumor growth without causing toxicity, suggesting its potential as a chemotherapeutic agent for melanoma.
FRONTIERS IN ONCOLOGY
(2022)
Article
Chemistry, Medicinal
Razia Banoo, Vijay K. Nuthakki, Mohd Abdullaha, Mohit Sharma, Sandip B. Bharate
Summary: This study investigated the benzyl piperidinyl-linked benzyl aminobenzamide as a dual cholinesterase inhibitor. The compound showed inhibition of acetylcholinesterase and butyrylcholinesterase and crossed the blood-brain barrier. It also inhibited the self-aggregation of amyloid-beta. These findings suggest the potential of benzamide 8c1 for further investigation in preclinical models of Alzheimer's disease.
DRUG DEVELOPMENT RESEARCH
(2022)
Article
Chemistry, Applied
Abhishek Gour, Ashish Dogra, Mahendra K. Verma, Mahir Bhardwaj, Dilpreet Kour, Ashiya Jamwal, Bapi Gorain, Mukesh Kumar, Bhavna Vij, Ajay Kumar, Utpal Nandi
Summary: The study investigated the protective effect of a herbal compound called NPM on acute lung injury (ALI). Results showed that NPM improved lung damage caused by ALI and had antioxidant and anti-inflammatory effects. The findings provide potential insights into Ayurvedic recommendations for boosting immunity during ALI.
NATURAL PRODUCT RESEARCH
(2023)
Article
Chemistry, Applied
Bashir Ahmad Lone, Nitika Sharma, Dilpreet Kour, Anil Bhushan, Dixhiya Rani, Ajay Kumar, Prashant Kumar Gupta, Prasoon Gupta
Summary: In this study, two compounds, baicalin and naringenin, were identified as potent inhibitors of sickling in SCD patients' blood samples. These flavonoids have shown promising potential for the management of SCD crisis where effective therapy is lacking.
NATURAL PRODUCT RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Sadhana Sharma, Sushil Choudhary, Sukhleen Kaur, M. Venkat Reddy, Niranjan Thotac, Amarinder Singh, Surrinder Koul, Inshad Ali Khan, Zabeer Ahmed, Ajay Kumar
Summary: This study synthesized derivatives of dihydronaphthyl and evaluated their inhibition activity on P-glycoprotein (P-gp). PGP-41 exhibited the most potent P-gp inhibition activity in colorectal adenocarcinoma LS-180 cells and chemoresistant ovarian cell line NCI/ADR-RES. PGP-41 sensitized NCI/ADR-RES cells to paclitaxel treatment by downregulating P-gp expression and increasing intracellular concentration of paclitaxel.
CHEMICO-BIOLOGICAL INTERACTIONS
(2023)
Article
Chemistry, Multidisciplinary
Chetan Kumar, Gourav Chandan, Manoj Kushwaha, Amit Kumar, Sukhleen Kaur, Ajay Kumar, Govind Yadav, Sumeet Gairola, Ram A. Vishwakarma, Naresh Kumar Satti, Mahendra Kumar Verma
Summary: The present study isolated, identified, and quantified biomarker compounds in plant extracts of Habenaria intermedia D. Don. The compounds were isolated using column chromatography and characterized using NMR and mass spectral data. A new quantitative method using HPLC-PDA was established, resulting in the isolation and characterization of seven compounds. The study also revealed the immunomodulatory and anti-inflammasome activities of these compounds, suggesting their potential utilization as functional health supplements.
Correction
Chemistry, Multidisciplinary
Shreyans K. Jain, Anup S. Pathania, Rajinder Parshad, Chandji Raina, Asif Ali, Ajai P. Gupta, Manoj Kushwaha, Subrayashastry Aravinda, Shashi Bhushan, Sandip B. Bharate, Ram A. Vishwakarma
Summary: Correction is made for the study on the antileukemic naphthocoumarins, Chrysomycins A-C, from Streptomyces sporoverrucosus by Shreyans K. Jain et al. in 2013. The authors further discovered new antileukemic synthetic compounds from the Streptomyces sporoverrucosus and characterized them.
Article
Chemistry, Organic
Faiza Diaba, Gisela Trenchs
Summary: The first violet light-mediated synthesis of gamma- and delta-lactams from N-alkenyl trichloroacetamides is reported in this paper. The reactions are conducted in tetrahydrofuran or 2-methyltetrahydrofuran as the sole solvent without catalysts or additives, under non-anhydrous conditions in an air atmosphere where the solvent serves as the radical initiator.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
Article
Chemistry, Organic
Feroze Hussain, Sajjad Ahmed, Ashiq Hussain Padder, Qazi Naveed Ahmed
Summary: This study reports a novel and efficient one-pot synthesis method for mixed phosphorotrithioates, which does not require supplementary additives and shows broad applicability.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
Article
Chemistry, Organic
Hyunjin Oh, Ikyon Kim
Summary: A new 1,2,4-triazole-pyrrolo[1,2-a]pyrazine hybrid system, 6-acylpyrrolo[1,2-a][1,2,4]triazolo[5,1-c]pyrazine, was synthesized using a catalyst-free method. This method involved sequential exposure of pyrrole-2-carbonitrile-derived substrates to DMF-DMA and acyl hydrazide, resulting in the formation of acylated pyrazine and 1,2,4-triazole rings, enabling the installation of various substituents at specific positions on the core skeleton.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
Article
Chemistry, Organic
Ming Yan, Si-fan Wang, Yong-po Zhang, Jin-zhong Zhao, Zhuo Tang, Guang-xun Li
Summary: Here we developed an efficient photocatalytic approach for the convenient preparation of sulfinamides. The reaction allows for the gram-scale preparation of sulfinamides and the one-pot synthesis of various sulfonyl amides.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
Article
Chemistry, Organic
Farzaneh Bandehali-Naeini, Zahra Tanbakouchian, Noushin Farajinia-Lehi, Nicolas Mayer, Morteza Shiri, Martin Breugst
Summary: Two tandem catalytic systems were developed for the synthesis of novel 3,4-disubstituted maleimides using the same Ugi adducts. Different maleimide structures can be synthesized using either Pd or Cu catalysis.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
Article
Chemistry, Organic
Tanya Raghava, Anjan Chattopadhyay, Subhadeep Banerjee, Nivedita Sarkar
Summary: Amine substitution of two ortho fluorine atoms of tetrafluoroterephthalonitrile through SNAr chemistry is easily achievable. But further fluorine substitution is only possible under forcing conditions, yielding valuable fluorophores for bioimaging.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
Review
Chemistry, Organic
Anju Chadha, Santosh Kumar Padhi, Selvaraj Stella, Sowmyalakshmi Venkataraman, Thangavelu Saravanan
Summary: Alcohol dehydrogenases are enzymes that use cofactors for oxidation or reduction reactions of alcohols or carbonyl compounds. They are utilized in green chemistry and have applications in the production of pharmaceuticals. Recombinant enzymes have solved the challenge of producing purified enzymes in large quantities. Engineered alcohol dehydrogenases have been used in asymmetric synthesis in industry. Various methods have been established for regenerating expensive cofactors to make the enzymatic process more efficient and economically viable.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)