Design and Synthesis of Natural Antibacterial Derivatives for Ocular Tuberculosis: A Comprehensive Review

Isaiah Osei Duah Junior^1,2,3Gabriel Amankwah^4,5,6Josephine Ampong¹Sherlene Brown⁷Bernice Lebene Tettey⁴Hubert Osei Acheampong⁸Ruth Awuku Boahemaa⁹Cynthia A. Danquah^10*

• ¹Department of Optometry and Visual Science, College of Science, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
• ²Department of Psychology, John R. and Kathy R. Hairston College of Health and Human Sciences, North Carolina Agricultural and Technical State University, NC 27403, Greensboro, United States
• ³Department of Biological Sciences, College of Science, Purdue University, IN 47906, West Lafayette, United States
• ⁴Department of Chemistry, College of Science, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
• ⁵Department of Chemistry, College of Science, Purdue University, IN 47906, West Lafayette, United States
• ⁶Nesvard Institute of Molecular Sciences, Accra, Ghana
• ⁷Department of Internal Medicine, University of Texas Medical Branch, TX 77500, Galveston, United States
• ⁸Graduate Program in Anatomy and Cell Biology, Wayne State University School of Medicine, MI 48201, Detroit, United States
• ⁹Department of Family and Consumer Science, North Carolina Agricultural and Technical State University, NC 27411, Greensboro, United States
• ¹⁰Department of Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, College of Health Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana

Ocular tuberculosis (OTB) is an underrecognized extrapulmonary manifestation of Mycobacterium tuberculosis infection that can result in irreversible vision loss. Current systemic therapies, including isoniazid, rifampicin, pyrazinamide, and ethambutol, are often inadequate in achieving therapeutic intraocular concentrations and may pose ocular toxicity risks. The eye's unique anatomical and physiological barriers, including the cornea, blood–aqueous, and blood– retinal barriers, limit drug penetration, particularly to the posterior segment. This paper explores the potential of natural antibacterial compounds as candidates for ocular TB therapy, emphasizing on rational design, chemical modification, and targeted delivery. Phytochemicals, plant-derived alkaloids, flavonoids, terpenoids, quinone, polyphenols, and saponins offer promising antibacterial scaffolds, which can be optimized for ocular bioavailability and safety through structural modification, prodrug strategies, and hybridization with other bioactive moieties. Advanced delivery systems, including nanoparticles, liposomes, nanogels, sustained-release implants, and in situ gelling systems, can overcome ocular barriers and maintain therapeutic drug concentrations. Preclinical evaluation using in vitro, ex vivo, and in vivo ocular models is critical to assess antimicrobial efficacy, pharmacokinetics, and toxicity. Clinical translation requires careful integration with systemic therapy, robust trial design, and navigation of regulatory frameworks, with particular attention to resource-limited settings. Future directions include computational modeling, personalized therapy, and global accessibility to ensure equitable implementation. By combining natural product chemistry, innovative delivery strategies, and translational research, next-generation ocular TB therapies have the potential to prevent vision loss and improve patient outcomes worldwide.