Article
Chemistry, Medicinal
Kyle D. Farrell, Yamin Gao, Deborah A. Hughes, Robin Henches, Zhengchao Tu, Michael Perkins, Tianyu Zhang, Craig L. Francis
Summary: A series of 3-methoxy-2-phenylimidazo[1,2-b]pyridazine derivatives were found to be highly active against autoluminescent Mycobacterium tuberculosis (Mtb) and Mycobacterium marinum (Mm) in vitro. SAR analysis revealed that the most active compounds exhibited in vitro MIC90 values generally around 0.63-1.26 μM against Mtb and Mm, but were inactive against Mtb in vivo (mice) due to very short metabolic half-lives when incubated with mouse liver microsomes, possibly through oxidative cleavage of the imidazole moiety.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Organic
Biswajit Mondal, Prasanjit Ghosh, MrinalKanti Kundu, Tapas Kumar Das, Sajal Das
Summary: In this study, the palladium-catalyzed arylation of the inert beta-C(sp(2))-H bond of carboxylic acid derivatives is reported for the first time, using 8-aminoimidazo[1,2-a]pyridine (AIP) as a novel removable directing group. The protocol is scalable, exhibits high levels of beta-site selectivity, and tolerates a broad spectrum of functional groups.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2021)
Article
Chemistry, Physical
Kabelo B. Dilebo, Njabulo J. Gumede, Winston Nxumalo, Thabe M. Matsebatlela, Dikgale Mangokoana, Ngaoko R. Moraone, Bernard Omondi, Richard M. Mampa
Summary: A series of quinazolines were successfully synthesized via Sonogashira cross-coupling and dechloroamination reactions, showing potential anti-Mycobacterium tuberculosis properties with promising minimum inhibitory concentrations. The possible mode of interaction with Mtb was theoretically explained through molecular protein 3ZXR, revealing the compounds' SAR to MtGS.
JOURNAL OF MOLECULAR STRUCTURE
(2021)
Article
Chemistry, Medicinal
Heng Wang, Jing Bi, Yuan Zhang, Miaomiao Pan, Qinglong Guo, Genhui Xiao, Yumeng Cui, Song Hu, Chi Kin Chan, Ying Yuan, Takushi Kaneko, Guoliang Zhang, Shawn Chen
Summary: This study identifies linsitinib, a clinical-stage drug originally targeting kinase IGF1R/IR, as a potent inhibitor of the essential glutamine synthase in Mycobacterium tuberculosis. Linsitinib also improves autophagy flux and reduces intracellular growth of Mtb. These findings suggest that targeting ATP-dependent enzymes like glutamine synthase could be a novel approach for anti-TB therapy.
ACS INFECTIOUS DISEASES
(2022)
Article
Biochemistry & Molecular Biology
Rui Liu, Kate Marshall, Rui Ma, Kim Lien Thi Pham, Gauri Shetye, Zhihao Liu, Sanghyun Cho, Hyunyoung Jeong, Scott G. Franzblau, Garrett C. Moraski, Marvin J. Miller
Summary: This article describes the research on the design and synthesis of potent deuterated IAPs and investigates the effect of deuteration on metabolism through microsomal stability studies.
BIOORGANIC CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Yogesh Mahadu Khetmalis, Surendar Chitti, Anjani Umarani Wunnava, Banoth Karan Kumar, Muthyala Murali Krishna Kumar, Sankaranarayanan Murugesan, Kondapalli Venkata Gowri Chandra Sekhar
Summary: Thirty-four imidazo-[1,2-a)pyridine amides and imidazo[1,2-a]pyridine sulfonamides were designed and synthesized based on the molecular hybridization strategy. The compounds were evaluated for anti-tubercular activity and cytotoxicity, and their binding pattern and stability were studied using molecular docking and molecular dynamics simulations.
RSC MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Organic
Biswajit Mondal, Prasanjit Ghosh, MrinalKanti Kundu, Sajal Das
Summary: In this study, a novel method was developed for regioselective ortho-C(sp(2))-H arylation in aqueous medium using 8-AIP as a promising and removable bidentate directing group/auxiliary. The protocol demonstrated excellent functional group tolerance and exclusive site-selectivity, providing a rapid route to a library of unsymmetrical amides in good to excellent yields.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2021)
Review
Biochemistry & Molecular Biology
Sauvik Samanta, Sumit Kumar, Eswar K. K. Aratikatla, Sandeep R. R. Ghorpade, Vinayak Singh
Summary: Tuberculosis (TB) has been the deadliest infectious disease for the past 2000 years, claiming more lives than any other infectious disease. In 2021, TB caused 1.6 million deaths globally, ranking second only to COVID-19. Unfortunately, TB drug discovery research was neglected in the last few decades of the twentieth century. Recently, the World Health Organization has taken action to develop new TB drugs, with imidazopyridine being recognized as a potential drug scaffold and showing significant activity against multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB).
RSC MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Organic
Meng-Qi Ping, Ming-Zhong Guo, Rui-Tao Li, Zi-Chen Wang, Cheng Ma, Li-Rong Wen, Shao-Fei Ni, Weisi Guo, Ming Li, Lin-Bao Zhang
Summary: This study has successfully developed an efficient electrochemical method for the [3 + 2] annulation of imidazo[1,2-a]pyridines with alkynes, using traceless electrons as green reagents. It leads to the synthesis of a large class of polycyclic heteroaromatics with good yields and a broad substrate scope under mild and green conditions.
Review
Chemistry, Medicinal
Milan Urban, Veronika Slachtova, Lucie Brulikova
Summary: Mycobacterial energy metabolism, particularly the oxidative phosphorylation pathway, has become increasingly important as a molecular target for the development of new anti-TB drugs. Small organic molecules targeting this pathway have shown promising activity against latent and resistant TB strains, with FDA-approved inhibitors confirming the value of targeting mycobacterial energy metabolism.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Infectious Diseases
Sacha J. Pidot, Jessica L. Porter, Troy Lister, Timothy P. Stinear
Summary: Nontuberculosis mycobacterial (NTM) infections are on the rise globally, with limited treatment options available. However, the development of new antimycobacterial drugs shows promise in addressing this issue. The novel antibiotic SPR719 has shown activity against NTM species, with a MIC range of 0.125-4 μg/ml, comparable to commonly used antimycobacterial antibiotics such as rifampicin and clarithromycin. Further evaluation of SPR720 for NTM infection treatment is warranted.
PLOS NEGLECTED TROPICAL DISEASES
(2021)
Article
Biology
Muhammad Hassam, Jawwad A. Shamsi, Ajmal Khan, Ahmed Al-Harrasi, Reaz Uddin
Summary: This study utilizes computational methods to predict highly active drug molecules, using machine learning models to optimize the screening of active molecules. The best performing model is selected for data screening experiments, aiding in enhancing the drug discovery process against Mycobacterium tuberculosis.
COMPUTERS IN BIOLOGY AND MEDICINE
(2022)
Article
Pharmacology & Pharmacy
M. Korycka-Machala, M. Kawka, J. Lach, R. Plocinska, A. Bekier, B. Dziadek, A. Brzostek, P. Plocinski, D. Strapagiel, M. Szczesio, K. Gobis, J. Dziadek
Summary: Recently, it has been discovered that 4-substituted picolinohydrazonamides with hydrophilic cyclic amines exhibit potent antimycobacterial activity in vitro. Two selected compounds, 2,4-disubstituted pyridine derivatives 11 and 15, showed significant bactericidal activity against Mycobacterium tuberculosis within human macrophages and biofilm-forming tubercle bacilli.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Wagdy M. Eldehna, Mahmoud A. El Hassab, Nahla A. Abdelshafi, Fatma Al-Zahraa Sayed, Mohamed Fares, Sara T. Al-Rashood, Zainab M. Elsayed, Marwa M. Abdel-Aziz, Eslam B. Elkaeed, Mahmoud Elsabahy, Noura G. Eissa
Summary: WF-208, inspired by the anti-tubercular activity of isoniazid and 5-bromoisatin, demonstrated potent efficacy against MDR and XDR strains of M. tuberculosis. Incorporation of WF-208 into nanosized vesicles not only enhanced stability and sustained antimicrobial effects, but also significantly increased its anti-mycobacterial activity.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2022)
Article
Toxicology
Adinarayana Nandikolla, Singireddi Srinivasarao, Yogesh Mahadu Khetmalis, Banoth Karan Kumar, Sankaranarayanan Murugesan, Gauri Shetye, Rui Ma, Scott G. Franzblau, Kondapalli Venkata Gowri Chandra Sekhar
Summary: This study designed and synthesized twenty-eight novel 1,2,3-triazole analogues of imidazo-[1,2-a]-pyridine-3-carboxamide, with some compounds showing promising anti-tubercular activity. Compound 10b was found to be the most active, exhibiting MIC values of 13.74 μg/mL in MABA and 24.63 μg/mL in LORA.
TOXICOLOGY IN VITRO
(2021)
Article
Chemistry, Organic
Anna Karin Belfrage, Johan Gising, Fredrik Svensson, Eva Akerblom, Christian Skold, Anja Sandstrom
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2015)
Article
Biochemistry & Molecular Biology
Anna Karin Belfrage, Eldar Abdurakhmanov, Eva Akerblom, Peter Brandt, Anna Oshalim, Johan Gising, Anna Skogh, Johan Neyts, U. Helena Danielson, Anja Sandstrom
BIOORGANIC & MEDICINAL CHEMISTRY
(2016)
Article
Chemistry, Medicinal
Anneli Nordqvist, Gavin O'Mahony, Maria Friden-Saxin, Marlene Fredenwall, Anders Hogner, Kenneth L. Granberg, Anna Aagaard, Stefan Backstrom, Anders Gunnarsson, Tim Kaminski, Yafeng Xue, Anita Dellsen, Eva Hansson, Pia Hansson, Ida Ivarsson, Ulla Karlsson, Krister Bamberg, Majlis Hermansson, Jennie Georgsson, Bo Lindmark, Karl Edman
Review
Gastroenterology & Hepatology
Daniel Muthas, Anna Reznichenko, Clare A. Balendran, Gerhard Bottcher, Ib Groth Clausen, Carina Karrman Mardh, Tomas Ottosson, Mohib Uddin, Thomas T. MacDonald, Silvio Danese, Mark Berner Hansen
SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY
(2017)
Article
Pharmacology & Pharmacy
Claire Grant, Lorna Ewart, Daniel Muthas, Damian Deavall, Simon A. Smith, Glen Clack, Pete Newham
TOXICOLOGY AND APPLIED PHARMACOLOGY
(2016)
Correction
Biotechnology & Applied Microbiology
Tudor I. Oprea, Cristian G. Bologa, Soren Brunak, Allen Campbell, Gregory N. Gan, Anna Gaulton, Shawn M. Gomez, Rajarshi Guha, Anne Hersey, Jayme Holmes, Ajit Jadhav, Lars Juhl Jensen, Gary L. Johnson, Anneli Karlson, Andrew R. Leach, Avi Ma'ayan, Anna Malovannaya, Subramani Mani, Steven L. Mathias, Michael T. McManus, Terrence F. Meehan, Christian von Mering, Daniel Muthas, Dac-Trung Nguyen, John P. Overington, George Papadatos, Jun Qin, Christian Reich, Bryan L. Roth, Stephan C. Schurer, Anton Simeonov, Larry A. Sklar, Noel Southall, Susumu Tomita, Ilinca Tudose, Oleg Ursu, Dusica Vidovic, Anna Waller, David Westergaard, Jeremy J. Yang, Gergely Zahoranszky-Kohalmi
NATURE REVIEWS DRUG DISCOVERY
(2018)
Article
Biotechnology & Applied Microbiology
Tudor I. Oprea, Cristian G. Bologa, Soren Brunak, Allen Campbell, Gregory N. Gan, Anna Gaulton, Shawn M. Gomez, Rajarshi Guha, Anne Hersey, Jayme Holmes, Ajit Jadhav, Lars Juhl Jensen, Gary L. Johnson, Anneli Karlson, Andrew R. Leach, Avi Ma'ayan, Anna Malovannaya, Subramani Mani, Stephen L. Mathias, Michael T. McManus, Terrence F. Meehan, Christian von Mering, Daniel Muthas, Dac-Trung Nguyen, John P. Overington, George Papadatos, Jun Qin, Christian Reich, Bryan L. Roth, Stephan C. Schurer, Anton Simeonov, Larry A. Sklar, Noel Southall, Susumu Tomita, Ilinca Tudose, Oleg Ursu, Dusica Vidovic, Anna Waller, David Westergaard, Jeremy J. Yang, Gergely Zahoranszky-Kohalmi
NATURE REVIEWS DRUG DISCOVERY
(2018)
Article
Chemistry, Multidisciplinary
Rebecka Isaksson, Jens Lindman, Johan Wannberg, Jessica Sallander, Maria Backlund, Dhaniel Baraldi, Robert Widdop, Mathias Hallberg, Johan Aqvist, Hugo Gutierrez de Teran, Johan Gising, Mats Larhed
Article
Biochemistry & Molecular Biology
Johan Wannberg, Johan Gising, Jens Lindman, Jessica Salander, Hugo Gutierrez-de-Teran, Hanin Ablahad, Selin Hamid, Alfhild Gronbladh, Iresha Spizzo, Tracey A. Gaspari, Robert E. Widdop, Anders Hallberg, Maria Backlund, Anna Lesniak, Mathias Hallberg, Mats Larhed
Summary: A series of meta-substituted acetophenone derivatives containing N-(alkyloxycarbonyl)thiophene sulfonamide fragments were synthesized, with a tert-butylimidazole derivative identified as a potent AT2 receptor ligand. This ligand demonstrated high stability and affinity for the AT2 receptor, as well as potential as an AT2 receptor agonist.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Editorial Material
Biotechnology & Applied Microbiology
Marie Olliver, Laura Griestop, Diarmaid Hughes, Anna Karin Belfrage, Johan Gising, Pawel Baranczewski, Carina Vingsbo Lundberg, Anders Karlen
Summary: ENABLE is an antibacterial drug discovery and development consortium formed in 2014 as part of the Innovative Medicines Initiative (IMI) New Drugs for Bad Bugs (ND4BB) programme. With the project soon ending, a brief overview of its achievements, strengths, and weaknesses is provided.
NATURE REVIEWS DRUG DISCOVERY
(2021)
Article
Biochemistry & Molecular Biology
Tamal Roy, Nadia N. Petersen, Greeshma Gopalan, Johan Gising, Mathias Hallberg, Mats Larhed
Summary: Ligands with a benzimidazole ring demonstrate high affinity and receptor selectivity. The substitution of bulky groups in the 2-position enhances these properties. The stability of ligands in human liver microsomes varies depending on the terminal group.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Jens Lindman, Greeshma Gopalan, Carlos Palo-Nieto, Peter Brandt, Johan Gising, Mats Larhed
Summary: In this study, a new catalytic reaction has been reported for the synthesis of a series of N-methylspiroindolines with high yield and diastereoselectivity. The stereocontrol around the spirocarbon was rationalized by density functional theory calculations and confirmed through X-ray crystallography.
Article
Biochemistry & Molecular Biology
Frida Stam, Sara Floren Lind, Anja Schroff, Sofia Zelleroth, Erik Nylander, Johan Gising, Alfhild Gronbladh, Mats Larhed, Mathias Hallberg
Summary: Angiotensin IV is a bioactive peptide that inhibits insulin-regulated aminopeptidase. HA08, a potent IRAP inhibitor, can restore cell viability in cells damaged by hydrogen peroxide.
CURRENT ISSUES IN MOLECULAR BIOLOGY
(2022)
Meeting Abstract
Chemistry, Multidisciplinary
Jens Lindman, Rebecka Isaksson, Johan Wannberg, Jessica Sallander, Maria Backlund, Dhaniel Baraldi, Robert Widdop, Mathias Hallberg, Johan Aqvist, Hugo Gutierrez de Teran, Johan Gising, Mats Larhed
ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
(2019)
Article
Biochemistry & Molecular Biology
Maria De Rosa, Lu Lu, Edouard Zamaratski, Natalia Szalaj, Sha Cao, Henrik Wadensten, Lena Lenhammar, Johan Gising, Annette K. Roos, Douglas L. Huseby, Rolf Larsson, Per E. Andren, Diarmaid Hughes, Peter Brandt, Sherry L. Mowbray, Anders Karlen
BIOORGANIC & MEDICINAL CHEMISTRY
(2017)
Article
Chemistry, Medicinal
Shibin Zhao, Julian Maceren, Mia Chung, Samantha Stone, Raphael Geiben, Melissa L. Boby, Bradley S. Sherborne, Derek S. Tan
Summary: Antibiotic resistance is a major threat to public health, with Gram-negative bacteria presenting unique challenges due to their low permeability and efflux pumps. Limited understanding of the chemical rules for overcoming these barriers hinders antibacterial drug discovery. Efforts to address this issue, such as screening compound libraries and using cheminformatic analysis, have led to the design of sulfamidoadenosines with diverse substituents, showing potential utility in accumulation in Escherichia coli.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Jichun Li, Qing Li, Shuai Xia, Jiahuang Tu, Longbo Zheng, Qian Wang, Shibo Jiang, Chao Wang
Summary: This study successfully developed a short peptide mimetic as a MERS-CoV fusion inhibitor by reproducing the key recognition features of the HR2 helix. The resulting 23-mer lipopeptide showed comparable inhibitory effect to the 36-mer HR2 peptide HR2P-M2. This has important implications for developing short peptide-based antiviral agents to treat MERS-CoV infection.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Krista Jaunsleine, Linda Supe, Jana Spura, Sten van Beek, Anna Sandstrom, Jessica Olsen, Carina Halleskog, Tore Bengtsson, Ilga Mutule, Benjamin Pelcman
Summary: Beta(2)-adrenergic receptor agonists can stimulate glucose uptake by skeletal muscle cells and are therefore potential treatments for type 2 diabetes. The chirality of compounds has a significant impact on the activity of these agonists. This study found that certain synthesized compounds showed higher glucose uptake activity. These findings provide important information for the design of novel beta(2)AR agonists for T2D treatment.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Xin Xu, Jia Chen, Guan Wang, Xiaojuan Zhang, Qiang Li, Xiaobo Zhou, Fengying Guo, Min Li
Summary: The study focuses on EZH2, a promising therapeutic target for various types of cancers. Researchers designed and synthesized a series of novel derivatives aiming to enhance the EZH2 inhibition activity. Among them, compound 28 displayed potent EZH2 inhibition activity and showed high anti-proliferative effects in lymphoma cell lines and xenograft mouse models. The study suggests that compound 28 has potential as a therapeutic candidate for EZH2-associated cancers.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Wei Zhang, Wei Liu, Ya-Dong Zhao, Li-Zi Xing, Ji Xu, Rui-Jun Li, Yun-Xiao Zhang
Summary: This study developed a series of aromatic amide derivatives based on Rhein and investigated their inhibitory activity against alpha-Syn aggregation. Two of these compounds showed promising potential in treating Parkinson's disease by stabilizing alpha-Syn's conformation and disassembling alpha-Syn oligomers and fibrils.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Mani Sharma, S. S. S. S. Sudha Ambadipudi, Neeraj Kumar Chouhan, V. Lakshma Nayak, Srihari Pabbaraja, Sai Balaji Andugulapati, Ramakrishna Sistla
Summary: Therapeutically active lipids in drug delivery systems can enhance the safety and efficacy of treatment. The liposome formulation created using synthesized biologically active lipids showed additive anti-cancer effects and reduced tumorigenic potential.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
