Periodontal diseases, such as gingivitis and periodontitis, are inflammatory diseases triggered by pathogenic bacteria that lead to damage of the soft tissue and bone supporting the teeth. Amongst the identified oral periodontopathogenic bacteria, Porphyromonas gingivalis is able to enhance oral dysbiosis, which is an imbalance in the beneficial commensal and periodontal pathogenic bacteria that induces chronic inflammation. Given the critical role of oral pathogenic bacteria like P. gingivalis in the pathogenesis of periodontitis, local and/or systemic antibacterial therapy has been suggested to treat this disease, especially in its severe or refractory forms. Nevertheless, the majority of the antibacterial agents currently used for the treatment of periodontal diseases are broad-spectrum, which harms beneficial bacterial species that are critical in health, inhibit the growth of pathogenic bacteria, contribute in protecting the periodontal tissues to damage and aid in its healing. Thus, the development of more effective and specific antibacterial agents is needed to control oral pathogens in a polymicrobial environment. The strategies for the development of novel antibacterial agents include natural product isolation as well as synthetic and semi-synthetic methodologies. This review presents an overview of the periodontal diseases gingivitis and periodontitis along with current antibacterial treatment options (i.e., classes of antibacterial agents and the mechanism(s) of resistance that hinder their usage) used in periodontal diseases that specifically target oral pathogens such as P. gingivalis. In addition, to help medicinal chemists gain a better understanding of potentially promising scaffolds, this review provides an in-depth coverage of the various families of small molecules that have been investigated as potential anti-P. gingivalis agents, including novel families of compounds, repositioned drugs, as well as natural products.
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