For about a century, antibacterial drugs known as antibiotic have helped control and annihilate many for the life-threatening microorganisms that make us sick. However, in recent years, antibiotics have been losing their punch against several types of bacteria. A number of bacterial strains are now impervious with current therapeutics. The manner we use antibiotics for treatment regimens has helped pave the way in the emergence (and resurgence) of new drug-resistant “superbugs”.

Superbugs are bacteria strains resistant to several types of antibiotics. Drug-resistant forms of tuberculosis and staph infections are just a few of the dangers we now face. Antibiotics are among the most commonly prescribed drugs to treat a wide range of infectious diseases. Sadly, many antibiotics prescribed to people and to animals are not necessary. The abuse and misapplication of antibiotics help to create drug-resistant superbugs.

In the past, some of the most dangerous superbugs have been confined to health care settings. One common superbug increasingly growing outside many hospitals is the methicillin-resistant Staphylococcus aureus (MRSA). These bacteria are not affected by methicillin and related antibiotics.

Alarmingly, recent reports f outbreaks of drug resistant diseases have brought tuberculosis back to our attention. TB mortality levels are once again at the top of the hill and has been ascribed to the AIDS epidemic. Which has created new and highly susceptible population. Given that investment in antibiotics in general has waned over recent years, current drug discovery researchers have been unable to respond to the resurgence of drug-resistant strains.

Pharmacological research and drug discovery critically depend on access to large variety of small molecules that have good binding properties for biological molecules. Literature reports show the continuing and important contributions of nature as a source of prototype compounds that have provided the foundation and inspiration for the synthetic development of new antibiotic drugs. Because the elucidation of new chemotypes for drug development remains an urgent matter in many therapeutic areas, innovative strategies are being developed for natural products to contribute to their full range of chemical diversity to the drug discovery flow. Such strategies include the preparation of natural product mixtures by combinatorial biosynthesis and related techniques.

Recently, approaches have been geared to generate bioactive compounds through chemical diversification of inactive natural product mixtures. The approach banks on the introduction of changes in a significant proportion of the molecules present in a natural extract without previous knowledge of the exact composition of the starting material. The strategy to modify as many compounds as possible in complex natural mixtures (i.e., plant extracts) of mostly unknown composition is to focus on the transformation of chemical functionalities which are very common in natural products and this expected to be present in a significant proportion of the members of the mixture.

Among the pharmacologically interesting plants and the subject of our research I the Philippine endemic Annonaceous species, Uvariavalderramensisor “usog” in Tagalog. Our main goal is to provide more potent chemical derivatives through chemical diversification or incorporation of bioactive handles to natural product scaffolds present in the fractions of the extract of Uvariavalderramensis.

Results of our studies show promising inhibitory properties of the constituents in the extract against Mycovacterium tuberculosis H37Rv, the causative agent of TB and Staphylococcus aureus. Extensive phytochemical efforts paved the discovery of new bioactive natural products with activity against slow and fast-growing strains of TB. In addition, extension of our study by enhancing the anti-infective properties of sub-extract-derived fractions through introduction of pharmaco-relevant functionalities has led to the generation and discovery of new anti-tuberculosis and anti-staphylococcal compounds.

The preparation of chemically-altered extracts by chemical manipulation of reactive groups present in natural products opens opportunities to use known and unknown natural scaffolds for the generation of potentially antibiotic compounds. This can be envisaged as a method to reconstruct these platforms through directed adornment with unnatural groups or sub-structures.

If those functionalities were transformed into chemical groups that are rarely produced by nature, one could complement nature’s synthetic capabilities and therefore could lead to the discovery of more potent antibacterial drugs. Given the range of chemical structures and potency of biological activity presented in our study, it is clear that natural products will play an important role in the development of new generations of anti-infective drugs.

Indeed, despite the considerable challenges that are posed by the “superbugs”, our recent contribution and efforts to find new drugs may lend hopes that science will deliver on the promise of eradicating life-threatening infectious diseases.

Written by:
Allan Patrick G. Macabeo
University of Santo Tomas

Published by:
Department of Science and Technology-Science and Technology Information Institute (DOST-STII)