The importance of boron to med chem is undeniable. It is also crowned with Nobel prize in 1979 by recognizing prof. Herbert C. Brown’s contribution to boron chemistry. However, the incorporation of boron in durg molecules are long neglected, probably part due to the electron deficient atom tends to coordination to electron rich atoms(oxygen, nitrogen, etc). Which will cause the instability of the moeluces. On the other hand, boron offers several advantages over traditional carbon-based drugs:
Reversible Covalent Bonding: Boron can form reversible covalent bonds with biological targets, leading to stronger and more specific interactions compared to simple non-covalent binding. This can result in more potent and selective drugs.
Mimicking Transition States: Boron’s electronic structure allows it to mimic the geometry of the transition state (intermediate state) of enzymatic reactions. By mimicking this state, boron-containing drugs can inhibit enzymes more effectively.
Targeting “Undruggable” Targets: Some biological targets, particularly those with flat surfaces, have historically been difficult to target with traditional drugs. Boron’s ability to form covalent bonds with different geometries makes it possible to target these previously “undruggable” sites.
Tuning Properties: The properties of boron-containing drugs, such as potency and selectivity, can be fine-tuned by modifying the surrounding chemical groups attached to the boron atom. This allows for the creation of drugs with tailored properties for specific therapeutic needs.
Safety Profile: Boron is a naturally occurring element found in some foods and the environment. While some boron compounds can be toxic, research suggests that carefully designed boron-containing drugs can have good safety profiles.
As of Dec. 2023, there are five FDA-approved boron-containing drugs, also known as boron-based pharmaceuticals. These drugs have been developed for various therapeutic purposes, including anti-inflammatory, anti-cancer, antiviral, and antibacterial applications.
| Drug name | Original Developer | FDA approval year | Indicaton |
| Bortezomib (Velcade) | Millennium Pharmaceuticals | 2003 | multiple myeloma and mantle cell lymphoma. It works by inhibiting the proteasome, a cellular complex involved in protein degradation, leading to apoptosis (programmed cell death) of cancer cells. |
| Tavaborole (Kerydin) | Anacor | 2014 | n antifungal medication used topically to treat onychomycosis (fungal nail infections). It inhibits fungal protein synthesis by interfering with tRNA synthetase enzymes, leading to fungal cell death. |
| Ixazomib (Ninlaro) | Takeda | 2015 | treatment for multiple myeloma. It works by inhibiting a protein (XPO1) involved in the transport of other proteins within cancer cells, disrupting their growth and survival. |
| Crisaborole (Eucrisa) | Anacor | 2016 | treats mild to moderate atopic dermatitis (eczema). Its mechanism of action is still under investigation, but it’s believed to modulate the immune response in the skin. |
| Vaborbactam (in combination with meropenem as Vabomere) | Melinta | 2017 | A beta-lactamase inhibitor used in combination with an antibiotic (meropenem) to treat complicated urinary tract infections and certain hospital-acquired bacterial pneumonia. Vaborbactam protects meropenem from being broken down by certain enzymes produced by bacteria, making the antibiotic more effective. |
Besides the above drugs, boron also showed promising cooperative therapeutic applicaiton with radiopharmaceuticals, ie. boron neutron capture therapy ( BNCT). BNCT is a unique cancer treatment that utilizes boron-containing compounds. Patients are administered a boron compound, which preferentially accumulates in tumor cells. The tumor is then irradiated with low-energy neutrons, causing the boron to undergo nuclear fission, releasing high-energy particles that selectively destroy the tumor cells while sparing surrounding healthy tissue.
These examples highlight the diversity of boron-containing drugs and their potential therapeutic applications in medicine. The unique properties of boron hold promise for the development of new and effective drugs for a wide range of diseases. As research continues, we can expect to see more boron-containing drugs emerge in the future.
However, it’s essential to note that the development and use of boron-containing drugs require careful consideration of their safety, efficacy, and potential side effects.