M. Iqbal Choudhary and Atta-ur-Rahman
International Center for Chemical and Biological Sciences, (H.E.J. Research Institute of Chemistry and Dr. Panjwani Center for Molecular Medicine and Drug Research) University of Karachi, Karachi-75270, Pakistan
Modern drug development is an expensive and lengthy process, which requires over $ 1.8-2.0 billion worth of investment, and focused work of a large interdisciplinary team of scientists, involving years of studies, and screening of a large chemical space. Unfortunately this situation has out-numbered and out-resourced the academic institutions and pharmaceutical R & D of developing nations. The role of academic institutions in drug development, particularly in developing countries, is gradually diminishing. As a result, several diseases, affecting the lives of poor population of the South remain untreated. This situation demands a major soul searching by pharmaceutical scientists who wish to serve the humanity through the skills they posses. Overall change in paradigm in drug development is required, which create space for academic researchers and R & D workers of developing nations to contribute in the discovery and development of drugs against diseases affecting their regions. This change must involve the effective use of indigenous knowledge and resources. Natural products and their traditional uses can play a very important role in drug development for poors by researchers of developing world. During the presentation, results of our studies on natural products will be presented to support the argument that the knowledgebased research on the natural products is a key to discover potential drug candidates at low cost.
Multidrug resistance is a challenging problem for the healthcare sector and is very common in familiar pathogens, such as vancomycin-resistant enterococci and Staphylococcus aureus. Exposure and inappropriate use of the antibiotics is the measure cause of MDR, both in developed and developing regions. Our study, focusing on the discovery of natural and synthetic compounds, active against multidrug resistant bacteria Staphylococcus aureus and Pseudomonas aeruginosa have resulted in the identification of several novel and potent inhibitors of MDR Staphylococcus aureus, (EMRSA-17, EMRSA-16, MRSA-252, and Pak clinical isolates) from natural sources. Resistance-reversal studies at molecular level were carried out by employing flow cytometric and microscopic techniques. Synergistic and partial synergistic effects of these compounds, in combination with antibiotics, were investigated. This work has so far resulted in the identification of several novel ″helper molecules”, which can increase the efficacy of existing antibiotics to over 1000-fold in some cases.
Diabetes is one of the largest threats for public health in the new millennium, and its impact is felt most severely in developing countries. It is a chronic disease that occurs when the pancreas does not produce enough insulin, or when the body cannot effectively use the insulin it produces. Hyperglycaemia, or raised blood sugar, is a common feature of uncontrolled diabetes which leads to serious damage to many of the body's systems, especially the nerves and blood vessels. Diabetic patients are prone to long-term complications, such as retinopathy, cataract, atherosclerosis, neuropathy, nephropathy and impaired wound healing. Most of these complications are related to standard changes in tissues proteins by their non-enzymatic bindings with sugars molecules. Current treatments of diabetes are largely ineffective in achieving the normal sugar levels and delaying the onset of late diabetic complication. Therefore, there is an urgent need for new strategies for the treatment of diabetes, and its prevention against complications.
Among different therapeutic interventions, the discovery of effective α-glucosidase inhibitors and antiglycating agents are considered to be the most important one, based on modern knowledge about the disease at molecular level. Primary focus of these studies has been to discover lead molecules by using appropriate conventional and mechanism-based biological screening techniques. As a result, a large number of potent antiglycation agents, and a-glucosidase inhibitors of natural origin were discovered and structure-activity relationship studies were conducted. Many of these compounds represent new examples of inhibitors of α-glucosidase and protein glycation.