BSc (Pharm) (Hons), University of Singapore
PhD, National University of Singapore
Department of Pharmacy, National University of Singapore
18 Science Drive 4, Singapore 117543
Tel: +65 6516 2654
Fax: +65 6779 1554
Teaching Activities in NUS
I am involved in the teaching of three modules : a general education module (GEK 2506) Drugs and Society and two medicinal chemistry modules, Principles of Medicinal Chemistry (PR 3101) and Advanced Topics in Medicinal Chemistry (PR 5212).
My research interests are in the area of designing and synthesizing novel compounds with the purpose of optimizing biological activity and understanding their modes of action by structure-activity relationship studies and biochemical / pharmacological approaches. Among other factors, our design approaches are made with drug properties in mind. These are the intrinsic properties of molecules and include permeability, solubility and microsomal stability. A “useful” chemical entity designed for biological activity should not only be optimized for its pharmacological property but also the “drug-like” properties of the molecule. Where applicable, structure-based design approaches (molecular docking) are used to propose structures for synthesis and explain structure-activity relationship (SAR) trends.
Lead discovery of antimycobacterial agents
Tuberculosis (TB) is a global scourge accounting for nearly 1.3 million deaths annually. Every year, nearly 8 million new cases are identified, with most cases centered in Asia. New drugs are urgently required for the treatment of TB for many reasons. Foremost is the emergence of highly resistant organisms that cannot be eradicated by current drugs. Although limited to approximately 1% of all TB cases presently, multidrug resistant TB is more difficult and costly to treat than drug susceptible TB and patient outcomes are generally poor. Furthermore, the causative organism Mycobacterium tuberculosis exhibits phenotypic drug resistance, that is, resistance is not attributed to genetic mutations but the non-replicating persistent state of the organism. These dormant bacilli are not killed by any of the current drugs for TB. An epidemiological synergy exists between TB and HIV infections, with co-infection increasing the morbidity of both TB and HIV-AIDS in afflicted persons. Concurrent administration of drugs for TB and HIV is complicated by shared toxicities, drug-drug interactions and pharmacokinetic considerations. Thus, the challenges for TB drug discovery are unique.
Our laboratory is involved in lead discovery of potent antimycobacterial agents with novel modes of action and acceptable pharmaceutical profiles that warrant further investigations as potential clinical candidates. Our approach involves screening focused chemical libraries for antimycobacterial activity on surrogate mycobacterial strains (M smegmatis, M bovis BCG), identifying early hits with MIC 90 in low micromolar range and optimizing activity by directed synthesis. Pharmaceutical profiling will be concurrently carried out to establish structure-property relationships that would guide in compound selection for iterative modification and optimization. The research approach is summarized in the following figure: