Spirooxindole Radiotracers

Natural products and their active constituents are an important source of inspiration for medicinal chemists to design and synthesize modern diagnostic or therapeutic agents with advanced physical and biological properties. Spirooxindoles represent a unique class of compounds characterized by a spiro-fused oxindole core. The scaffold is widely recognized in medicinal chemistry due to its presence in numerous natural products. The conformational rigidity and defined stereochemistry of spiro-compounds enhance their ability to selectively interact with the biological targets, making them responsible for a broad range of pharmacological properties, including anticancer, antimicrobial, antiviral, and anti-inflammatory effects.

The available cancer treatment drugs often face limitations such as drug resistance, off-target toxicity, variable response, and limited efficacy in advanced or aggressive tumors. For example, paclitaxel and cisplatin provide decent treatment response, but impose serious side effects, including bone marrow suppression and nephrotoxicity due to their non-selective nature. On the other hand, the anti-proliferative drugs such as tamoxifen are moderate in action, but not very efficacious in eradicating the tumor completely. Hence, many cancers remain incurable, and even in treatable cases, recurrence and metastasis remain major clinical challenges. Therefore, the discovery of novel agents with improved target selectivity in addition to strong efficacy is important for the development of new diagnostic and therapeutic drugs, and considerable efforts are being devoted towards this direction.

We, the King Saud University and Cyclotron and Radiopharmaceuticals department at KFSH&RC, are willing to design and synthesize some halogenated spirooxindoles that may be used as potential diagnostic and therapeutic agents. We aim to design molecules that are more selective to cancer, have fewer side effects, and are less prone to drug resistance. After synthesis, the molecules will be labeled with a Positron Emission Tomography (PET) radionuclide such as fluorine-18 (18F), gallium-68 (68Ga), Zirconium-89 (89Zr), and Copper-64 (64Cu) or with therapeutic radionuclides such as Actinium-225 (225Ac), lutetium-177 (177Lu) for their biological evaluation. The project may lead towards the development of mono- or bispecific spirooxindoles, which may have better biological affinity and improved selectivity to several tumors, including the breast, colorectal, pancreatic, and lung cancer.