H3D University of Cape Town UCT

H3D University of Cape Town UCT

H3D has state of the art laboratory equipment and access to modern instrumentation housed in the Department of Chemistry, UCT.

 

This includes unlimited access to SciFinder Scholar search engine, microanalytical service, gas-liquid chromatography, analytical and preparative high pressure liquid chromatography (HPLC) instruments, liquid chromatography-mass spectrometry (LC-MS) and other routine facilities. Additionally, major items of modern physical equipment include nuclear magnetic resonance (NMR) spectrometers (Mercury 300 MHz, Unity 400 MHZ and a recently ordered Bruker 600 MHz multi-nuclear and solid state spectrometers), a gas chromatograph-coupled mass spectrometer, mid-infra red (IR) spectrometers, UV-visible spectrophotometers, X-ray generators and single-crystal diffractometers (four-circle and CCD detector) for crystallographic studies, LC. H3D also has a computational laboratory for computer aided drug design (CADD) within the Department of Chemistry with full access to hardware and software required to undertake CADD approaches.

Within our medicinal chemistry synthesis laboratories there is also a CEM Discover Automated Microwave, GeneVac, two Waters preparative HPLC systems, Agilent 1200 HPLC/MSD system, Biotage flash chromatography system, ISCO flash chromatography system, fraction collectors, Radleys carousel 6/12 systems for array chemistry, UV lamps, sonicators, rotary evaporators, heater stirrers, fumehoods, cold-room, refrigerators, freezers and laboratory glassware necessary to carry out multi-step organic synthesis.

Medicinal Chemistry

Medicinal chemistry is a discipline that require its practitioners to not only be outstanding organic chemists, but to have a thorough understanding of the effect chemical entities and their modification will have on the human body.

Medicinal chemistry is about integrating multiple disciplines such as synthetic chemistry, computational chemistry, physicochemical properties, metabolism & pharmacokinetics, biological properties, patents & publications and safety. H3D has several teams of these skilled professionals that are led by experienced pharmaceutical industry professionals. We routinely do hit validation, formal hit assessment, hit-to-lead and lead optimization of novel chemical entities.

CADD

Computer-Aided Drug Design integrates state of the art technologies to help decrease the time and cost of discovering new drugs. Using specialised software packages, computational chemists integrate the available structural biology and physical properties of a drug target to develop in silico models which are used to help guide medicinal chemistry projects. In silico models can help reduce the time to select a drug candidate in a number of ways including: assessing the druggability of a biological target, identifying new drug leads via virtual screening, improving the target affinity and physiochemical properties of a lead, and helping to identify hotspots for drug metabolism.

H3D DMPK and Malaria (Division of Pharmacology Groote Schuur Hospital, Medical Campus UCT)

The Pharmacology laboratory has technologies and associated equipment and expertise to profile compounds for their drug metabolism and pharmacokinetics (DMPK) properties as reflected in the processes of Absorption, Distribution, Metabolism, Excretion (ADME).

This initially involves screening compounds for kinetic solubility as well as metabolic stability in human, mouse and rat liver microsomes. Compounds that demonstrate good microsomal metabolic stability are tested in vivo for oral bioavailability and plasma half-life in rat/mouse. Some of the microsomes. Compounds that demonstrate good microsomal metabolic stability are tested in vivo for oral bioavailability and plasma half-life in rat/mouse. Some of the ADME assays routinely run in our laboratory include: UV/VIS, kinetic solubility, metabolic stability (human, rat and mouse microsomes), metabolite identification, chemical stability, lipophilicity, plasma protein binding, CYP inhibition, hepatocyte stability assays and rodent PK.VIS, kinetic solubility, metabolic stability (human, rat and mouse microsomes), metabolite identification, chemical stability, lipophilicity, plasma protein binding, CYP inhibition, hepatocyte stability assays and rodent PK.

DMPK

Our capabilities in the area of in vitro and in vivo Drug Metabolism and Pharmacokinetics (DMPK) include in vitro ADMET (Absorption, Distribution, Metabolism, Excretion and Toxicology) and in vivo PK (Pharmacokinetics) evaluation in rodents to aid in decision making with respect to compound progression. These studies generate data that provides vital information to medicinal chemistry programmes which are critical in designing new drug leads. H3D maintains and contributes to an in vitro ADMET and in vivo pharmacokinetics capability at UCT, and is one of very few centres of its kind in Africa that has this capability integrated with medicinal chemistry.

Malaria Biology

H3D has a dedicated parasitology team to perform blood stage screening for malaria and access to secondary screening in gametocytes through our partnership with the Council for Scientific and Industrial Research (CSIR), University of Pretoria (UP), University of the Witwatersrand (Wits) and NHLS.

H3D TB Biology (IDM Building, Medical Campus UCT)

Our facilities at the Institute of Infectious Disease and Molecular Medicine (IDM) include a dedicated laboratory for assay development and media preparation and full access to a BSL-3 Laboratory. The laboratory is equipped for preparation of media and compounds with balances, laminar flow hood and a Hamilton Starlet liquid handling robot. The BSL-3 Laboratory suite is fully equipped with dedicated equipment for the microbiological growth and molecular manipulation of M. tuberculosis sufficient for whole cell M. tuberculosis screening.

H3D has a dedicated TB biology team housed at the IDM and the TB biology team routinely conducts whole cell screening, biology triage and target identification studies for the TB projects.

In addition, H3D has access to TB assays at the University of Stellenbosch (SUN), the Africa Health Research Institute (AHRI) and The National Health Laboratory Service (NHLS).