Emerging strategies for microbial screening of novel chemotherapeutics

Sarethy, Indira P.; Jeevanandam, Jaison; Danquah, Michael K.

doi:10.1016/j.molstruc.2022.132419

Cited by 3 publications

(2 citation statements)

References 80 publications

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“…ELSD-based approaches, in particular, demonstrated success quantifying natural products lacking chromophore and have been coupled with HPLC, MS, and UV for library preparation [ 102 ]. Srivastava et al discussed various strategies for microbial screening to identify chemotherapeutics along with available bioinformatics pipelines [ 103 ].…”

Section: Natural Product Library (Npl) Screening For Antibacterial Dr...mentioning

confidence: 99%

High-Throughput Screening of Natural Product and Synthetic Molecule Libraries for Antibacterial Drug Discovery

Ayon

2023

Metabolites

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Due to the continued emergence of resistance and a lack of new and promising antibiotics, bacterial infection has become a major public threat. High-throughput screening (HTS) allows rapid screening of a large collection of molecules for bioactivity testing and holds promise in antibacterial drug discovery. More than 50% of the antibiotics that are currently available on the market are derived from natural products. However, with the easily discoverable antibiotics being found, finding new antibiotics from natural sources has seen limited success. Finding new natural sources for antibacterial activity testing has also proven to be challenging. In addition to exploring new sources of natural products and synthetic biology, omics technology helped to study the biosynthetic machinery of existing natural sources enabling the construction of unnatural synthesizers of bioactive molecules and the identification of molecular targets of antibacterial agents. On the other hand, newer and smarter strategies have been continuously pursued to screen synthetic molecule libraries for new antibiotics and new druggable targets. Biomimetic conditions are explored to mimic the real infection model to better study the ligand–target interaction to enable the designing of more effective antibacterial drugs. This narrative review describes various traditional and contemporaneous approaches of high-throughput screening of natural products and synthetic molecule libraries for antibacterial drug discovery. It further discusses critical factors for HTS assay design, makes a general recommendation, and discusses possible alternatives to traditional HTS of natural products and synthetic molecule libraries for antibacterial drug discovery.

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Section: Natural Product Library (Npl) Screening For Antibacterial Dr...mentioning

confidence: 99%

High-Throughput Screening of Natural Product and Synthetic Molecule Libraries for Antibacterial Drug Discovery

Ayon

2023

Metabolites

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“…Over the past two decades, no new class of antibiotics has been introduced into clinical practice [ 3 ]; therefore, the search for promising antimicrobial drugs and methods for their application remains a pressing issue in chemistry and medicine [ 4 , 5 , 6 , 7 ]. One of the most popular strategies comprises chemical modification of drugs that have previously been approved for the treatment of bacterial infections.…”

Section: Introductionmentioning

confidence: 99%

3-Amino-Substituted Analogues of Fusidic Acid as Membrane-Active Antibacterial Compounds

et al. 2023

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Fusidic acid (FA) is an antibiotic with high activity against Staphylococcus aureus; it has been used in clinical practice since the 1960s. However, the narrow antimicrobial spectrum of FA limits its application in the treatment of bacterial infections. In this regard, this work aims both at the study of the antimicrobial effect of a number of FA amines and at the identification of their potential biological targets. In this way, FA analogues containing aliphatic and aromatic amino groups and biogenic polyamine, spermine and spermidine, moieties at the C-3 atom, were synthesized (20 examples). Pyrazinecarboxamide-substituted analogues exhibit a high antibacterial activity against S. aureus (MRSA) with MIC ≤ 0.25 μg/mL. Spermine and spermidine derivatives, along with activity against S. aureus, also inhibit the growth and reproduction of Gram-negative bacteria Escherichia coli, Acinetobacter baumannii, and Pseudomonas aeruginosa, and have a high fungicidal effect against Candida albicans and Cryptococcus neoformans. The study of the membrane activity demonstrated that the spermidine- and spermine-containing compounds are able to immerse into membranes and disorder the lipidsleading to a detergent effect. Moreover, spermine-based compounds are also able to form ion-permeable pores in the lipid bilayers mimicking the bacterial membranes. Using molecular docking, inhibition of the protein synthesis elongation factor EF-G was proposed, and polyamine substituents were shown to make the greatest contribution to the stability of the complexes of fusidic acid derivatives with biological targets. This suggests that the antibacterial effect of the obtained compounds may be associated with both membrane activity and inhibition of the elongation factor EF-G.

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A Comprehensive Review of Ethnomedical Uses, Phytochemical Studies, and Properties of Holy Basil (Ocimum sanctum Linn.)

Maru,

Sharma,

Mishra

et al. 2023

Pharmacological Benefits of Natural Agents

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Environment-derived products such as secondary metabolites from plants and animals also provide a humongous chemical space for potential candidates for drug discovery. It is a known fact that over 80% of the approved drugs have either been derived or are directly used in natural products. Ocimum sanctum L. or holy basil has been considered a majestic reservoir for medically potential phytochemicals and tremendous therapeutic applications. Basil was the most widely used medicinal plant in ancient civilizations in Africa, Central and South America, and Middle Eastern countries of Asia such as India, China, and Malaysia. Different parts of basil, such as leaves, stems, and roots, have shown various therapeutic activities. Phytochemicals derived from holy basil can be classified as terpenoid, flavonoid, phenolic acid, neolignan, phenylpropanoid, cerebroside, and coumarin. Bioinformatic and cheminformatic approaches such as target fishing and identification, pharmacophore-based modelling, and QSAR can be used to identify the potential targets.

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Emerging strategies for microbial screening of novel chemotherapeutics

Cited by 3 publications

References 80 publications

High-Throughput Screening of Natural Product and Synthetic Molecule Libraries for Antibacterial Drug Discovery

High-Throughput Screening of Natural Product and Synthetic Molecule Libraries for Antibacterial Drug Discovery

3-Amino-Substituted Analogues of Fusidic Acid as Membrane-Active Antibacterial Compounds

A Comprehensive Review of Ethnomedical Uses, Phytochemical Studies, and Properties of Holy Basil (Ocimum sanctum Linn.)

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