Background: Cancer is a grave health problem for the world as the global cancer burden rises to 14
million new cases with 8.2 million deaths every year which is expected to rise by 70% in the next 2 decades as
reported by the WHO.These steady rises in death demand for rapid developments in anti-cancer agents. Essential
oils, being natural and multi-component complex systems have recently attracted a lot of attention in this
search for novel anti-cancer agents.
Materials and Methods: The pharmaceutical attributes of essential oil components, specifically focusing on
their affinity towards COX, 5-LOX, AKT, MDM2, PDK1 and mTOR which defines the phosphatidylinositol-3-
kinase (PI3K) pathway, were assessed. 123 compounds present in essential oils of different plants were analyzed
for their drug like attributes which were then allowed to dock with PI3K dependent receptors crucial for the
development of cancer malignancies. Among them, 21 compounds were filtered possessing high druglikeness
with favourable metabolism offered by major cytochromeP450 isoforms. Finally, the best docked compounds
with highest binding affinities were employed for building a ligand based pharmacophore.
Being inhibitors of P-glycoproteins, these molecules also exhibited good absorption profiles and noncarcinogenic
properties. Further from these 21, six compounds were evaluated against A549 lung cancer cells.
Results: The pharmacophoric feature obtained can be applied for both designing and screening moieties for
active inhibitors of the phosphatidylinositol-3-kinase pathway specifically from essential oil compounds and
these final 21 compounds can be further promoted to studies for anti-cancer drug development. Among these,
six compounds exhibited promising inhibitory results against A549 lung cancer cells. Furthermore, immunoblotting
assay confirmed the efficacy of the compounds for inhibiting mTOR and AKT enzymes which are bandmasters
for downstream signaling of thePI3K pathway.
Conclusion: Methyl nonanoate, (R)-citronellol, cis-carveol (L-carveol), 3-methyl-Cyclohexanone, 4-carene and
thujopsene were finally screened for PI3K targeted anti-cancer therapies which may find direct application as
inhalers or sprays against lung cancer as these compounds are highly volatile.