‘Synthesis, Characterisation and Bioactivity of Quinoline-Based Molecular Hybrids’ was the title of research work that secured Dr Thandokazi Ntshele a PhD in Chemistry from the University of KwaZulu-Natal (UKZN).
Ntshele was supervised by the University’s Acting Dean of Research, Professor Neil Koorbanally.
“By employing a molecular hybridisation technique in a multi-target drug design strategy, Ntshele synthesised six novel libraries of quinoline-based drug-like molecules fusing quinoline with a pyrazole scaffold and using the 1,2,3-triazole scaffold as a bioactive linker with several aromatic acetamide moieties,” said Koorbanally. “The molecules were characterised using Nuclear Magnetic Resonance Spectroscopy and High-Resolution Mass Spectrometry.”
Her research identified several hit compounds as potential antidiabetic, anti-tubercular and antibacterial drugs.
Ntshele’s academic path began during her time as a National Research Foundation (NRF) intern at UKZN, where she was introduced to medicinal chemistry. This experience proved transformative, as it exposed her to the synthesis of bioactive heterocyclic compounds and ignited her interest in drug discovery.
“Medicinal chemistry aligned with my lifelong dream of improving lives through science,” she said. “UKZN’s strong emphasis on research excellence, coupled with opportunities for teaching and community contribution, motivated me to pursue doctoral studies and a future in academia.”
Ntshele explained that she combined parts of existing drug molecules to create new ‘hybrid’ compounds, with the goal of designing novel molecules that have improved activity while reducing unwanted side effects.
“By improving how these molecules interact with the body, my research aimed at developing safer, more effective medicines,” she said. “This approach was important as it built on what is already known to work while pushing boundaries to discover better and more affordable treatments.
“The ultimate aim was to identify hit compounds for further investigation as potential pharmaceuticals.”
Ntshele’s postgraduate journey not only allowed her to pursue her dream of medicinal chemistry research but also sparked a passion for teaching and mentorship. She gained extensive experience as a teaching assistant, laboratory demonstrator and Supplementary Instruction (SI) leader, earning recognition as the best SI leader in 2023 (second semester). This experience cemented her commitment to academia, and she now serves as a chemistry lecturer at Mangosuthu University of Technology.
Ntshele emphasised the broader significance of her research, noting its contribution to medicinal chemistry and drug discovery. Beyond identifying promising compounds, her work also provides valuable insights for other researchers.
“By documenting which hybrid molecules showed less potency in certain bioassays, my research supports future optimisation efforts and exploration in different bioassays,” she explained.
Her findings were shared widely through presentations at several academic platforms, including the South African Chemical Institute (SACI-KZN) Postgraduate Colloquium, the College of Agriculture, Engineering and Science’s Postgraduate Research and Innovation Symposium (PRIS), and the 16th Frank Warren Conference.
Looking ahead, Ntshele plans to continue growing in both research and academia. She aims to mentor and supervise postgraduate students, engage in local and international collaborations in drug discovery through organic synthesis and computational studies, and further develop her teaching expertise.
Her journey was not without challenges, and she credits her support system for helping her succeed. “Building a family while doing PhD research was no child’s play,” she said, acknowledging the encouragement she received from her husband, family, friends and colleagues. She also thanked Koorbanally, as well as the National Research Foundation (NRF), the College of Agriculture, Engineering and Science, and the Discipline of Chemistry staff for their support.
Koorbanally praised her resilience and achievements: “Thandokazi has done extremely well amid some very difficult circumstances. At the start of her PhD, we were hit with COVID and the lockdown. She persevered and completed her studies, achieving excellent results. She achieved all this while taking care of her young family. I am very proud of what she has accomplished.”
Outside her academic work, Ntshele enjoys spending time with her family, especially her children, Oluhle and Scebi, who continue to inspire her growth.
She encouraged aspiring scientists to remain determined: “Stay curious, stay resilient, and remember, every experiment is a step toward changing lives… your dreams are valid, and you can achieve them through hard work and resilience.”
She also expressed heartfelt appreciation to UKZN for providing an environment that enabled her to realise her dream.
Words: Sally Frost
Photograph: Sethu Dlamini