Researchers are on the verge of unleashing the power of the element boron
in a new generation of drugs and therapies, as decades of research begins to
bear fruit. Boron has to date far been one of biology's best kept secrets, but
is now attracting fast growing research interest and investment from the pharmaceutical
industry in the quest for novel drugs to tackle cancer and infectious diseases,
potentially overcoming limitations and side effects of current products.
Europe's response to the challenges and opportunities of boron chemistry in
medicine was discussed at a recent workshop, Biobor - Exploring New Opportunities
Of Boron Chemistry Towards Medicine. According to its convenor Zbigniew Lesnikowski,
the ESF workshop set the stage for a new era of boron therapies going beyond
the current application in cancer radiotherapy via boron neutron capture therapy
(BNCT), in which the element is used to help translate beams of neutrons into
radiation that targets tumour cells with less "collateral damage"
of surrounding healthy tissue.
"Yes, it became obvious during the workshop that there is now sufficient
knowledge and enough compounds to support a broad program of screening in the
quest for new antiviral and anticancer drugs containing essential boron components,"
said Lesnikowski. There was also scope for improving the application of BNCT
to cancer, but besides these two therapeutic avenues, boron also has vast potential
as the basis for compounds in diagnosis and biosensing, and also for novel bioorganic
materials, said Lesnikowski.
The applications in bio sensing, biomaterials, and drug development all spring
from the fundamental chemical properties of boron. All life is derived ultimately
from the element carbon, which lies next to boron in the periodic table of elements,
their respective atomic numbers being six and five. Boron compounds share some
similarities with carbon but also have important differences. It is the combination
of these similarities and differences that give boron its unique potential in
The important similarity is that boron, like carbon, combines with hydrogen
to form stable compounds that can participate in biochemical reactions and syntheses.
The key difference is that these compounds have distinctive geometrical shapes
and electronic charge distributions with greater 3D complexity than their carbon
based equivalents. As Lesnikowski put it, while organic carbon molecules tend
to comprise rings and chains, boron hydrides (compounds comprising mostly boron
and hydrogen) are made up of clusters and cages. This 3D structure makes it
possible to design molecules with specific charge distributions by varying their
internal structure, and this in turn brings the potential to tune how each part
of the structure relates to water molecules, and biomolecules present in living
organisms - if a component is hydrophobic, meaning it repels water, it is well
placed to enter cells by crossing the membrane. If it is hydrophilic, meaning
water-loving, it will naturally be soluble in water. The hydrophobic/hydrophilic
interactions also affect how a molecule makes contact and communication with
target proteins and nucleic acids.
The fact that novel boron compounds will be unfamiliar to life has potential
advantages for antibiotic drugs, since pathogens will be less able to develop
resistance against them. "Also the kind of interactions would be somehow
different from key-lock systems build up in living cell lines in nature for
billions of years," said Lesnikowski. "We can thus anticipate that
active substances would be less prone to development of resistance," said
Lesnikowski. "This is an obvious advantage of boron drugs." While
eventually pathogens such as bacteria and viruses are capable of evolving resistance
against almost any molecule that attacks them, Lesnikowski believed that it
would take longer for this to happen in the case of boron based compounds which
would therefore make it easier for humans to remain one step ahead rather than
struggling to keep pace as at present.
Apart from lack of knowledge over the potential, development of boron compounds
for medicine has been held back until now by the high cost of catalysts and
born based intermediate compounds used in the synthesis. Another important recent
development therefore was availability of lower cost intermediates in the synthesis
processes, according to Lesnikowski.
The ESF workshop Biobor - Exploring New Opportunities Of Boron Chemistry Towards
Medicine, was held in May 2008 in Lodz, Poland.