Bioactive Heterocyclic Compounds in Periodontitis: Pharmacological Evidence and Periodontal–Systemic and Cerebrovascular Interfaces in Older Adults: A Scoping Review

Abstract

Background/Objectives: Periodontitis is sustained by dysbiotic biofilms and dysregulated host responses, providing pharmacological targets for antimicrobial, host-modulating, phytochemical, regenerative, and locally delivered interventions. This scoping review mapped bioactive heterocyclic compounds investigated in periodontitis according to the structural family, pharmacological target, periodontal compartment, therapeutic maturity, selected periodontal–systemic interfaces, and a secondary geriatric cerebrovascular context. Methods: PubMed, Scopus, and the Web of Science Core Collection were searched for the principal review on 30 July 2026. Companion publications were linked at the study level, and design-specific appraisal was applied when sufficient methodological information was available. A separate cerebrovascular extension was searched on 6 August 2026 and analyzed independently of the principal evidence denominator. Results: The principal evidence map comprised 715 independent studies represented by 804 canonical eligible reports. Nitroimidazole-containing regimens formed the largest structural family (283 studies; 39.6%), followed by melatonin and indole-related agents (83; 11.6%), macrolides (77; 10.8%), berberine and isoquinoline-related compounds (29; 4.1%), and quinolones or fluoroquinolones (28; 3.9%). Human clinical evidence was concentrated mainly in established antimicrobial regimens, whereas many host-modulating, phytochemical, regenerative, signaling, and delivery-based approaches remained predominantly translational or preclinical. The detailed clinical subset comprised 48 human studies, including six core comparative studies; heterogeneity in population, regimen, treatment background, follow-up, outcome definition, and analysis unit precluded a clinically meaningful pooled estimate. Prespecified systemic interfaces included diabetes (35 studies), cardiovascular disease (13), and rheumatoid arthritis (2). The separate cerebrovascular component comprised 30 studies addressing the oral health burden, microbial and inflammatory associations, oral care interventions, and treatment safety considerations in older adults with ischemic stroke. Conclusions: The evidence supports compound- and formulation-specific interpretation rather than class-wide therapeutic recommendations. Clinical translation should integrate structural and mechanistic plausibility with periodontal target-site exposure, pharmacokinetic–pharmacodynamic evidence, clinically meaningful benefit, safety, and antimicrobial stewardship. The cerebrovascular evidence supports oral care integration and safety surveillance but does not establish causal periodontal effects on stroke, reperfusion outcomes, or thrombolysis eligibility.

The authors' abstract, as published at the source. Pharmaceuticals, 2026 · DOI ↗