Antibiotics: Conventional Therapy and Natural Compounds with Antibacterial Activity-A Pharmaco-Toxicological Screening

Abstract

Antibiotics are considered as a cornerstone of modern medicine and their discovery offers the resolution to the infectious diseases problem. However, the excessive use of antibiotics worldwide has generated a critical public health issue and the bacterial resistance correlated with antibiotics inefficiency is still unsolved. Finding novel therapeutic approaches to overcome bacterial resistance is imperative, and natural compounds with antibacterial effects could be considered a promising option. The role played by antibiotics in tumorigenesis and their interrelation with the microbiota are still debatable and are far from being elucidated. Thus, the present manuscript offers a global perspective on antibiotics in terms of evolution from a historical perspective with an emphasis on the main classes of antibiotics and their adverse effects. It also highlights the connection between antibiotics and microbiota, focusing on the dual role played by antibiotics in tumorigenesis. In addition, using the natural compounds with antibacterial properties as potential alternatives for the classical antibiotic therapy is discussed.

Keywords: antibiotic resistance; antibiotics; antitumor; classification; mechanism of action; natural compounds; toxicity.

Figure 1

The evolution of antibiotics.

Figure 2

Main classes of antibiotics and their general chemical structure.

Figure 3

Penicillin binding protein 4 (PBP4) from E. coli in complex with ampicillin (light green): HBs (Ser 30, Ser 62, Ser 420 and Asn 308) are depicted as green dotted lines, Pi-hydrophobic interactions (Phe 160) are depicted as purple dotted lines and electrostatic interactions (Lys 417) as orange dotted lines. The figure was built with Biovia Discovery Studio 4.1 using the PDB entry 2EX6 [29].

Figure 4

Molecular interactions of 50S ribosomal subunit targeting antibiotics, azithromycin (light blue), clindamycin (orange), quinupristin (pink) and linezolid (grey): HB are depicted as green dotted lines and hydrophobic interactions are depicted as purple dotted lines. The figure was built with Biovia Discovery Studio 4.1 using the PDB entries 1YHQ, 1YJW, 3CPW and 1YJN [31,32].

Figure 5

Small 30S ribosomal subunit from T. thermophilus in complex with tetracycline (red); zoomed image shows six different binding sites of tetracycline within the ribosomal subunit’s structure. The figure was built with Biovia Discovery Studio 4.1 using the PDB entry 1I97 [36].

Figure 6

Topoisomerase IV from S. pneumoniae in complex with moxifloxacin (red) and DNA (light green): classical HB are depicted as green dotted lines (DA1), C-H HBs are depicted as light green dotted lines and halogen interactions are depicted as blue dotted lines (DA5); hydrophobic interactions were omitted for better picture clarity. The figure was built with Biovia Discovery Studio 4.1 using the PDB entry 4Z3O.

Figure 7

Dihydrofolate reductase chain A (right) from S. aureus in complex with trimethoprim (green) and NADPH (orange) and dihydropteroate synthase chain B (left) from Y. pestis in complex with sulfamethoxazole (green) and 6-hydroxymethylpterin-diphosphate (orange). The figure was built with Biovia Discovery Studio 4.1 using the PDB entries 3TZF and 2W9S [40,41].

Figure 8

Graphical representation of broad- and narrow-spectrum antibiotics.

Figure 9

Schematic presentation of the main mechanisms of antibacterial action of plants.

Figure 10

Summary of the antitumor mechanisms of action of antibiotics.