Recent developments in natural product-based drug discovery for tuberculosis

Dong, Maryline; Pfeiffer, Bernhard; Altmann, Karl‐Heinz

doi:10.1016/j.drudis.2016.11.015

Cited by 36 publications

(19 citation statements)

References 56 publications

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“…In TB drug development, the study of natural bioactive products is inevitable. This is evidenced by the discovery of streptomycin (an aminoglycosidic drug isolated from Streptomyces griseus ) followed by rifamycin B (an ansamycin-type macrolactom), rifampicin (a potent inhibitor of RNA polymerase and a semisynthetic derivative of rifamycin B), and amikacin, kanamycin (aminoglycosides) and cycloserine in combination with capreomycin (second-line drug combinations) [ 4 , 5 ]. Recently, an outstanding review by Dong et al [ 5 ] vehemently emphasized the propensity of natural products and their derivatives for profound antimycobacterial efficacy.…”

Section: Introductionmentioning

confidence: 99%

Antimycobacterial, Enzyme Inhibition, and Molecular Interaction Studies of Psoromic Acid in Mycobacterium tuberculosis: Efficacy and Safety Investigations

Hassan

Šudomová²,

Berchová‐Bímová

et al. 2018

JCM

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The current study explores the antimycobacterial efficacy of lichen-derived psoromic acid (PA) against clinical strains of Mycobacterium tuberculosis (M.tb). Additionally, the inhibitory efficacy of PA against two critical enzymes associated with M.tb, namely, UDP-galactopyranose mutase (UGM) and arylamine-N-acetyltransferase (TBNAT), as drug targets for antituberculosis therapy were determined. PA showed a profound inhibitory effect towards all the M.tb strains tested, with minimum inhibitory concentrations (MICs) ranging between 3.2 and 4.1 µM, and selectivity indices (SIs) ranging between 18.3 and 23.4. On the other hand, the standard drug isoniazid (INH) displayed comparably high MIC values (varying from 5.4 to 5.8 µM) as well as low SI values (13.0–13.9). Interestingly, PA did not exhibit any cytotoxic effects on a human liver hepatocellular carcinoma cell line even at the highest concentration tested (75 µM). PA demonstrated remarkable suppressing propensity against UGM compared to standard uridine-5'-diphosphate (UDP), with 85.8 and 99.3% of inhibition, respectively. In addition, PA also exerted phenomenal inhibitory efficacy (half maximal inhibitory concentration (IC50) value = 8.7 µM, and 77.4% inhibition) against TBNAT compared with standard INH (IC50 value = 6.2 µM and 96.3% inhibition). Furthermore, in silico analysis validated the outcomes of in vitro assays, as the molecular interactions of PA with the active sites of UGM and TBNAT were unveiled using molecular docking and structure–activity relationship studies. Concomitantly, our findings present PA as an effective and safe natural drug plausible for use in controlling tuberculosis infections.

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Section: Introductionmentioning

confidence: 99%

Antimycobacterial, Enzyme Inhibition, and Molecular Interaction Studies of Psoromic Acid in Mycobacterium tuberculosis: Efficacy and Safety Investigations

Hassan

Šudomová²,

Berchová‐Bímová

et al. 2018

JCM

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“…Historically, natural products have been one of the most fruitful sources to obtain antibacterial lead compounds [ 5 , 68 – 69 ]. Griselimycin, a cyclic depsidecapeptide isolated from Streptomyces sp., was discovered fifty years ago, nonetheless, due to its poor pharmacokinetic properties and the availability of other drugs such as rifampicin, the optimization programme was abandoned [ 70 ]. Recently, the interest in neglected antibiotics with anti-tuberculosis potential resurged and led to further optimization and development studies around the griselimycin structure ( 21 , Fig.…”

Section: Reviewmentioning

confidence: 99%

Protein–protein interactions in bacteria: a promising and challenging avenue towards the discovery of new antibiotics

Carro¹

2018

Beilstein J. Org. Chem.

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Antibiotics are potent pharmacological weapons against bacterial infections; however, the growing antibiotic resistance of microorganisms is compromising the efficacy of the currently available pharmacotherapies. Even though antimicrobial resistance is not a new problem, antibiotic development has failed to match the growth of resistant pathogens and hence, it is highly critical to discover new anti-infective drugs with novel mechanisms of action which will help reducing the burden of multidrug-resistant microorganisms. Protein–protein interactions (PPIs) are involved in a myriad of vital cellular processes and have become an attractive target to treat diseases. Therefore, targeting PPI networks in bacteria may offer a new and unconventional point of intervention to develop novel anti-infective drugs which can combat the ever-increasing rate of multidrug-resistant bacteria. This review describes the progress achieved towards the discovery of molecules that disrupt PPI systems in bacteria for which inhibitors have been identified and whose targets could represent an alternative lead discovery strategy to obtain new anti-infective molecules.

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“…This review summarizes the discovery of the capuramycin-type nucleoside antibiotics; progress toward defining their biosynthetic pathway; and synthetic, semisynthetic, and biocatalytic studies aimed at generating analogs with potentially improved therapeutic value. For an in depth description of Mtb and tuberculosis, including the major challenges in drug discovery and development, we refer the reader to several excellent reviews [10,11,12,13,14] and publications cited herein.…”

Section: Introductionmentioning

confidence: 99%

Biosynthetic and Synthetic Strategies for Assembling Capuramycin-Type Antituberculosis Antibiotics

et al. 2019

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Mycobacterium tuberculosis (Mtb) has recently surpassed HIV/AIDS as the leading cause of death by a single infectious agent. The standard therapeutic regimen against tuberculosis (TB) remains a long, expensive process involving a multidrug regimen, and the prominence of multidrug-resistant (MDR), extensively drug-resistant (XDR), and totally drug-resistant (TDR) strains continues to impede treatment success. An underexplored class of natural products—the capuramycin-type nucleoside antibiotics—have been shown to have potent anti-TB activity by inhibiting bacterial translocase I, a ubiquitous and essential enzyme that functions in peptidoglycan biosynthesis. The present review discusses current literature concerning the biosynthesis and chemical synthesis of capuramycin and analogs, seeking to highlight the potential of the capuramycin scaffold as a favorable anti-TB therapeutic that warrants further development.

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Recent developments in natural product-based drug discovery for tuberculosis

Cited by 36 publications

References 56 publications

Antimycobacterial, Enzyme Inhibition, and Molecular Interaction Studies of Psoromic Acid in Mycobacterium tuberculosis: Efficacy and Safety Investigations

Antimycobacterial, Enzyme Inhibition, and Molecular Interaction Studies of Psoromic Acid in Mycobacterium tuberculosis: Efficacy and Safety Investigations

Protein–protein interactions in bacteria: a promising and challenging avenue towards the discovery of new antibiotics

Biosynthetic and Synthetic Strategies for Assembling Capuramycin-Type Antituberculosis Antibiotics

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