Linking Folk Knowledge with Science – Local Effort to Treat Global Diseases

Many natural products are highly evolved, specific, and effective gene products. Their diverse structural and stereochemical characteristics make them valuable templates for exploring novel molecular diversity. Nature has been the first source for cures for diseases and discomforts that have led to the foundation of many empirical therapeutic interventions. The majority of these have emerged from a plethora of terrestrial resources. Today, natural products and their derivatives represent over 50% of all drugs in clinical use. These drugs have been derived from diverse sources such as marine organisms, microorganisms, insects, and even animals. Natural products thus play a key role in global healthcare and the economy. Developing countries have long traditions of using plants and other natural products as remedies in their folk systems. Based on ethnomedicinal information, we selected several medicinal plants for bioassay-guided phytochemical investigations. These investigations resulted in the identification of a large number of bioactive constituents.

Epilepsy is among the leading neurological disorders in the world. Antiepileptic medicines, currently used in clinical practices, suffered from several problems. The prolonged use of synthetic epileptic drugs can cause neurotoxicity and other adverse side effects. Epileptic drugs only address the symptoms and do not treat the disease. Thus the ultimate goal is to develop ideal antiepileptic agents that are safe, specific, effective, orally bioavailable, and address the underlying problem. Based on this need, we screened a large number of medicinal plants used for the treatment of epilepsy from isolated valleys of Pakistan. As a result of systematic search, two potent antiepileptic constituents, isoxylitones A and B, along with their precursors, were isolated from Delphinium denudatum and Aconitum lavae. These studies have resulted in the identification of several classes of novel pharmacophores, which were then used to develop libraries of analogues to study their structure-activity relationship.

Urease is a metal containing enzyme present in a wide variety of organisms and associated with various pathological complications including peptic ulcer due to the Helicobacter pylori, present in stomach of the human. The available urease inhibitors are associated with many side effects and the computational studies disclose that they are not tightly bound with nickel atom ions and the amino acid residues of the active site pocket of the enzyme, therefore a search for more effective urease inhibitors is needed. We have discovered novel classes of many potent unease inhibitors. Computational and NMR studies were carried out on the coumarin/biscoumarin classes of compounds, which showed effective interactions with the active site of the urease enzyme.

Approaches toward the identification and development of treatment of global diseases by using folk knowledge will be presented, along with future prospects of this important branch of bioorganic and medicinal chemistry.