Chemical Space and Biological Target Network of Anti-Inflammatory Natural Products

Natural
products (NPs) are a promising source of anti-inflammatory
molecules for the development of drugs. Despite there being an abundance
of reports of large numbers of NPs having bioactivity in preliminary
cell-based assays of anti-inflammatory potential, their further optimization
and exploration are limited by the lack of a comprehensive understanding
of their effective scaffold structure or biological targets. To facilitate
target-based studies of anti-inflammatory NPs, the details of 665
NPs reported to have anti-inflammatory activity were extracted from
the literature and compiled into a data set we termed InflamNat. The
physicochemical properties of the NPs were analyzed, and the distribution
of their structures and scaffolds is presented. A compound-target
network was constructed from data in the PubChem Bioassay database.
The results demonstrated that, compared to natural anticancer compounds
in the NPACT database, compounds from the InflamNat data set contained
a comparable distribution of compound types but with a higher proportion
satisfying Lipinski’s rule. The all-atom structures and scaffold
of the compounds were diverse and barely convergent, with flavonoids
and triterpenoids being the groups with the greatest abundance. The
biological targets of the InflamNat compounds were identified as belonging
to a variety of protein families that had varied function. Seventy-two
percent of InflamNat compounds involved in the network were identified
as having more than one biological target, highlighting the potential
for multitarget anti-inflammatory drug development. In conclusion,
anti-inflammatory NPs provide a good library for the screening of
target-based leads or fragment-based drug design. Thus, elucidation
of their biological targets is fundamental for either a specific single-target
or multitarget drug development strategy. Meanwhile, a large proportion
of the chemical space of anti-inflammatory NPs is still unexplored,
with novel active scaffolds remaining to be discovered.