Anti-TB Drug Leads from Diverse Natural Sources

The present study aims to demonstrate two distinct approaches to searching for leads for anti-TB drug discovery from natural products, involving the assessment of ethnomedical information (Chapters 2 and 3) and fungi (Chapter 4). It consists of a total of five chapters. Chapter 1 introduces tuberculosis epidemiology and etiology. Furthermore, a general drug discovery process is detailed, together with the current status and difficulties of tuberculosis drug discovery and development, and how natural products can abate those difficulties and assist TB drug discovery. The ethnomedical approach described in Chapter 2, which comprises an extensive literature search based on the NAPRAERT database. NAPRALERT manages bibliographic and factual data on natural products including information on pharmacology, biological activity, taxonomic distribution, ethnomedicine, and chemistry of plant, microbial, and animal extracts. This chapter presents a Score Indexing system, developed as a rational approach to prioritize ethnobotanicals with given biological, phytochemical, and ethnobotanical information. Prioritization of ethnobotanical material assists in the search for useful sources in TB drug discovery. Chapter 3 provides a detailed description of the phytochemical and biological assessment of two naturally occurring anti-TB coumarins from the ethnomedical polypore mushroom Fomitopsis officinalis. Chapter 4 demonstrates the search for leads originating from fungi by the assessment of anti-TB activity and selectivity for a large fungal culture extract library (12,905 extracts) using whole-cell based high throughput screening (HTS) campaigns. Consequently, it comprises isolation, identification, and biological evaluation of the anti-TB natural product vermisporin, which was selected from HTS. Finally, chapter 5 summarizes the present study and introduces possible future directions