Discovery of 3H-pyrrolo[2,3-c]quinolines with activity against Mycobacterium tuberculosis by allosteric inhibition of the glutamate-5-kinase enzyme.

The therapeutic potential of 3H-pyrrolo[2,3-c]quinolines-the main core of Marinoquinoline natural products-has been explored for the development of new anti-TB agents. The chemical modification of various positions in this scaffold has led to the discovery of two pyrroloquinolines (compounds 50 and 54) with good in vitro activity against virulent strains of Mycobacterium tuberculosis (H37Rv, MIC = 4.1 μM and 4.

Structure-aided optimization of non-nucleoside M. tuberculosis thymidylate kinase inhibitors.

Mycobacterium tuberculosis thymidylate kinase (MtTMPK) has emerged as an attractive target for rational drug design. We recently investigated new families of non-nucleoside MtTMPK inhibitors in an effort to diversify MtTMPK inhibitor chemical space. We here report a new series of MtTMPK inhibitors by combining the Topliss scheme with rational drug design approaches, fueled by two co-crystal structures of MtTMPK in complex with developed inhibitors.

Matryoshka-type gastro-resistant microparticles for the oral treatment of Mycobacterium tuberculosis.

Aim: Production of Matryoshka-type gastroresistant microparticles containing antibiotic-loaded poly lactic-co-glycolic acid (PLGA) nanoparticles (NP) against Mycobacterium tuberculosis.

Materials & Methods: The emulsification and evaporation methods were followed for the synthesis of PLGA-NPs and methacrylic acid-ethyl acrylate-based coatings to protect rifampicin from degradation under simulated gastric conditions.

Results & Conclusion: The inner antibiotic-loaded NPs here reported can be released under simulated intestinal conditions whereas their coating protects them from degradation under simulated gastric conditions.

Boldine-Derived Alkaloids Inhibit the Activity of DNA Topoisomerase I and Growth of .

The spread of multidrug-resistant isolates of requires the discovery of new drugs directed to new targets. In this study, we investigated the activity of two boldine-derived alkaloids, seconeolitsine (SCN) and -methyl-seconeolitsine (-SCN), against . These compounds have been shown to target DNA topoisomerase I enzyme and inhibit growth of .

Synergy between Circular Bacteriocin AS-48 and Ethambutol against Mycobacterium tuberculosis.

The increasing incidence of multidrug-resistant strains and the very few drugs available for treatment are promoting the discovery and development of new molecules that could help in the control of this disease. Bacteriocin AS-48 is an antibacterial peptide produced by and is active against several Gram-positive bacteria. We have found that AS-48 was active against , including H37Rv and other reference and clinical strains, and also against some nontuberculous clinical mycobacterial species.

Structure Guided Lead Generation toward Nonchiral M. tuberculosis Thymidylate Kinase Inhibitors.

In recent years, thymidylate kinase (TMPK), an enzyme indispensable for bacterial DNA biosynthesis, has been pursued for the development of new antibacterial agents including against Mycobacterium tuberculosis, the causative agent for the widespread infectious disease tuberculosis (TB). In response to a growing need for more effective anti-TB drugs, we have built upon our previous efforts toward the exploration of novel and potent Mycobacterium tuberculosis TMPK ( MtTMPK) inhibitors, and reported here the design of a novel series of non-nucleoside inhibitors of MtTMPK. The inhibitors display hitherto unexplored interactions in the active site of MtTMPK, offering new insights into structure-activity relationships.

Discovery of antimicrobial compounds targeting bacterial type FAD synthetases.

The increase of bacterial strains resistant to most of the available antibiotics shows a need to explore novel antibacterial targets to discover antimicrobial drugs. Bifunctional bacterial FAD synthetases (FADSs) synthesise the flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD). These cofactors act in vital processes as part of flavoproteins, making FADS an essential enzyme.

Structure-Activity Relationships of Spectinamide Antituberculosis Agents: A Dissection of Ribosomal Inhibition and Native Efflux Avoidance Contributions.

Spectinamides are a novel class of antitubercular agents with the potential to treat drug-resistant tuberculosis infections. Their antitubercular activity is derived from both ribosomal affinity and their ability to overcome intrinsic efflux mediated by the Mycobacterium tuberculosis Rv1258c efflux pump. This study explores the structure-activity relationships through analysis of 50 targeted spectinamides.

Zanthoxylum capense constituents with antimycobacterial activity against Mycobacterium tuberculosis in vitro and ex vivo within human macrophages.

Ethnopharmacological Relevance: Zanthoxylum capense Thunb. (Rutaceae) is a medicinal plant traditionally used in Mozambique to treat tuberculosis.

Aims Of The Study: The main aim of the study was to find antimycobacterial lead compounds from Zanthoxylum capense.

Antimycobacterial evaluation and preliminary phytochemical investigation of selected medicinal plants traditionally used in Mozambique.

Ethnopharmacological Relevance: Several medicinal plants are traditionally used in Mozambique to treat tuberculosis and related symptoms.

Aims Of The Study: It was aimed to assess the in vitro antimycobacterial activity of crude extracts from fifteen medicinal plants and to reveal main classes of compounds which may account for the activity of extracts.

Methods And Materials: The plant materials were sequentially extracted by n-hexane, dichloromethane, ethyl acetate, and 70% ethanol.