Modern Trends in the Development of Natural and Synthetic Anti-Tuberculosis Drugs.

Tuberculosis (TB) pathogenesis is driven by the rapid proliferation of Mycobacterium tuberculosis bacilli, which breach host defenses to invade pulmonary tissue and precipitate active disease. While both natural and synthetic compounds have contributed to successful Mycobacterium tuberculosis (Mtb) therapies, researchers should now prioritize harnessing the synergistic effects of complementary treatments to maximize efficacy. Deploying natural and synthetic small molecules offers a powerful strategy to circumvent drug resistance, enhance Mycobacterium tuberculosis (MTB) therapeutic efficacy, and minimize the toxicities associated with conventional regimens and emerging PROTAC modalities. Consequently, clarifying how these natural and synthetic agents target resistant strains and alter associated genetic biomarkers is essential. This paper reviews recent advancements in natural and synthetic drugs, highlighting their structure-activity relationships to enhance anti-tuberculosis (TB) therapies. Additionally, we present a novel computational framework utilizing target prediction and probability scoring to identify high-potential synthetic compounds for future first-line TB regimens.