Review
Chemistry, Medicinal
Vladimir Finger, Martin Kufa, Ondrej Soukup, Daniele Castagnolo, Jaroslav Roh, Jan Korabecny
Summary: This review provides an overview of recent advances in the hit-to-lead drug discovery studies of pyrimidine-containing compounds with antitubercular activity, focusing on their structural diversity. The review discusses the targets and structure-activity relationships of different pyrimidine families in the first part and categorizes unexplored or speculative targets of antitubercular pyrimidine derivatives based on their structural types in the second part.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Physical
Sarra Riahi, Nizar Ben Moussa, Mohamed Lajnef, Nessrine Jebari, Ali Dabek, Radhouane Chtourou, Gregory Guisbiers, Sophie Vimont, Etienne Herth
Summary: Due to the excessive use of antibiotics in agriculture, bacteria have developed resistance, leading to the global spread of Antibiotic Resistant Bacteria and causing hundreds of thousands of deaths. This paper proposes the use of zinc oxide nanoparticles synthesized by a sol-gel technique as a potential solution against various types of bacteria, including Gram-negative, Gram-positive, and multidrug-resistant strains. The study determined the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC), and found that the zinc oxide nanoparticles were effective against several bacteria strains, including Escherichia coli, Klebsiella pneumoniae, and Staphylococcus aureus.
JOURNAL OF MOLECULAR LIQUIDS
(2023)
Article
Chemistry, Medicinal
Dongguang Fan, Bin Wang, Giovanni Stelitano, Karin Savkova, Rui Shi, Stanislav Huszar, Quanquan Han, Katarina Mikusova, Laurent R. Chiarelli, Yu Lu, Chunhua Qiao
Summary: By designing and synthesizing a series of 6-methanesulfonyl substituted BTZ analogues and introducing five-member aromatic heterocycles as linkers, we discovered a number of BTZ derived compounds with potent antitubercular activity, with two optimized compounds exhibiting increased aqueous solubility and stability.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Chemistry, Medicinal
Santosh Kumar Verma, Rameshwari Verma, Kothanahally S. Sharath Kumar, Laxmi Banjare, Afzal B. Shaik, Richie R. Bhandare, Kadalipura P. Rakesh, Kanchugarakoppal S. Rangappa
Summary: MRSA is becoming a major concern due to its rapid resistance development, prompting the need for novel antibiotics. The oxadiazole moiety serves as an interesting and adaptable molecular structure with potential for research and development as antibacterial agents. Studies on oxadiazole-containing derivatives as potent antibacterial agents against multidrug-resistant MRSA strains and exploring structure-activity relationships have been conducted, providing valuable insights for future drug development.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Apeng Wang, Shijie Xu, Yun Chai, Guimin Xia, Bin Wang, Kai Lv, Chao Ma, Dan Wang, Aoyu Wang, Xiaoyu Qin, Mingliang Liu, Yu Lu
Summary: A series of novel benzothiazinone derivatives containing a N-(amino)piperazine moiety, based on the structure of WAP-1902 discovered in the lab, were designed and synthesized as new anti-TB agents. Many compounds showed excellent in vitro activity against drug-sensitive MTB strain H37Rv and multidrug-resistant clinical isolates, with good safety index. Compound 1o, in particular, displayed low hERG cardiac toxicity and acceptable oral pharmacokinetic profiles, indicating its potential as a lead compound for future antitubercular drug discovery.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Tobias M. Bruetsch, Etienne Cotter, Daniel Lucena-Agell, Mariano Redondo-Horcajo, Carolina Davies, Bernhard Pfeiffer, Sandro Pagani, Simone Berardozzi, J. Fernando Diaz, John H. Miller, Karl-Heinz Altmann
Summary: In this study, five analogs of (-)-zampanolide (ZMP) were synthesized and their biochemical and cellular properties were evaluated. These analogs were derived from 13-desmethylene-(-)-zampanolide (DM-ZMP), which is as potent as ZMP in inhibiting cancer cell growth. Key steps in the synthesis of all compounds included the formation of a dioxabicyclo[15.3.1]heneicosane core and the establishment of the C(20) stereocenter. All modifications resulted in reduced cellular activity and microtubule-binding affinity compared to DM-ZMP, with varying degrees. The most potent analog, 2,3-dihydro-13-desmethylene zampanolide, showed cellular potency within a ninefold range of DM-ZMP.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Review
Biochemistry & Molecular Biology
Massimo Degano
Summary: Enzymes catalyzing the hydrolysis of the N-glycosidic bond in nucleosides and other ribosides (N-ribohydrolases, NHs) with diverse substrate specificities are found in all kingdoms of life. The unique features of the NH catalytic strategy and structure make these proteins attractive targets for diverse therapeutic goals in different diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Medicinal
Dorothy Semenya, Meir Touitou, Domiziana Masci, Camila Maringolo Ribeiro, Fernando Rogerio Pavan, Guilherme Felipe Dos Santos Fernandes, Beatrice Gianibbi, Fabrizio Manetti, Daniele Castagnolo
Summary: The exploration around the 2,5-dimethylpyrrole scaffold of antitubercular hit compound 1 has led to the discovery of new derivatives that are active against Mycobacterium tuberculosis and multidrug-resistant clinical isolates. Some of these derivatives showed promising cytotoxicity profiles and were effective in inhibiting the growth of intracellular mycobacteria.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Iredia D. D. Iyamu, Yingzhao Zhao, Prakash T. T. Parvatkar, Bracken F. F. Roberts, Debora R. R. Casandra, Lukasz Wojtas, Dennis E. E. Kyle, Debopam Chakrabarti, Roman Manetsch
Summary: A compound with promising antimalarial activity against chloroquine-resistant and chloroquine-sensitive strains of the parasite was identified through screening and structure-activity relationship studies. The essential features necessary for its activity and properties were determined through extensive research.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Article
Infectious Diseases
Saoussen Oueslati, Pierre Bogaerts, Laurent Dortet, Sandrine Bernabeu, Hend Ben Lakhal, Christopher Longshaw, Youri Glupczynski, Thierry Naas
Summary: The study evaluated the in vitro activity of cefiderocol against multidrug-resistant GN bacteria, including MR and PR isolates from France and Belgium. The results showed that cefiderocol demonstrated high susceptibility rates against a wide range of MDR GN pathogens.
Article
Chemistry, Multidisciplinary
Pratima Pandey, Rajashree Sahoo, Khusbu Singh, Sanghamitra Pati, Jose Mathew, Avinash Chandra Pandey, Rajni Kant, Ihn Han, Eun-Ha Choi, Gaurav Raj Dwivedi, Dharmendra K. Yadav
Summary: The study found that nanocomposites of graphene oxide exhibited antibacterial potential against multidrug-resistant bacteria, reducing the minimum inhibitory concentration (MIC) of tetracycline and inhibiting efflux pumps and biofilm synthesis.
Article
Chemistry, Medicinal
Apeng Wang, Na Du, Huijuan Song, Yuehao Zhang, Xijun Zhong, Jizhou Wu, Tiezheng Xue, Mingliang Liu, Bin Wang, Kai Lv, Yu Lu
Summary: This study focused on the synthesis of novel N-(amino)piperazinyl benzothiazinone derivatives as potential anti-TB agents with reduced in vivo toxicity. Compound 2c showed potent anti-MTB activity, low cardiac toxicity, low cell cytotoxicity, acceptable PK profiles, and low acute toxicity in mice, making it a promising lead compound for further drug discovery against tuberculosis.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Chemistry, Inorganic & Nuclear
Orlando Santoro, Carl Redshaw
Summary: Calixarenes are not only used in ion extraction, gas storage, and molecular sensors, but also extensively employed as ligands for metal complexation. Metallocalix[n]arenes have shown interesting catalytic activity in various reactions, often superior to other systems with different ligand scaffolds. This review summarizes the latest advances in the field post-2008, categorizing the complexes by metal center.
COORDINATION CHEMISTRY REVIEWS
(2021)
Article
Microbiology
Shilah Bonnett, Jo-Ann Jee, Somsundaram Chettiar, Yulia Ovechkina, Aaron Korkegian, Eric Greve, Joshua Odingo, Tanya Parish
Summary: In this study, analogs of our previously identified antitubercular compounds were tested for activity against M. tuberculosis and eukaryotic cells. Molecules with improved selectivity were identified. These molecules exhibited bactericidal activity against both replicating and nonreplicating bacteria but did not target protein secretion.
MICROBIOLOGY SPECTRUM
(2023)
Article
Microbiology
Weijie Wang, Xiaoli Zhu, Huan Luo, Zheng Wang, Anjin Hong, Jie Zeng, Li Li, Dai Wang, Xianming Deng, Xilin Zhao
Summary: As the increase in antimicrobial resistance continues, the options for effectively treating multidrug-resistant (MDR) Gram-negative infections are decreasing. Finding ways to enhance the lethality of old agents with unique molecular targets is important, as new antimicrobial development is increasingly difficult. This study showed that the old antibiotic bicyclomycin has good bacteriostatic activity against multiple clinical isolates of MDR Gram-negative pathogens. Additionally, the combination of bicyclomycin with doxycycline showed enhanced efficacy in inhibiting bacterial growth and in vivo killing, suggesting the potential of bicyclomycin-containing regimens as new treatment options for MDR Gram-negative infections caused by specific pathogens.
MICROBIOLOGY SPECTRUM
(2023)
