Anti-Cancer Agents in Medicinal Chemistry

(Formerly Current Medicinal Chemistry - Anti-Cancer Agents)

Michelle Prudhomme  
Universite Blaise Pascal - C.N.R.S
Aubiere Cedex


Volatile Inhibitors of Phosphatidylinositol-3-Kinase (PI3K) Pathway: Anti-Cancer Potential of Aroma Compounds of Plant Essential Oils

(E-pub Abstract Ahead of Print)

Author(s): Manobjyoti Bordoloi, Surovi Saikia, Bhaskor Kolita, Rajeev Sarmah.


Background: Cancer is a grave health problem for the world as global cancer burden rises to 14 million new cases with 8.2 million deaths every year which is expected to rise by 70% in next 2 decades as reported by 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 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 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 P-glycoprotein they also exhibited good absorption profiles and non-carcinogenic 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. Further, immunoblotting assay confirmed the efficacy of the compounds for inhibiting mTOR and AKT enzymes which are bandmasters for downstream signaling of the PI3K pathway. Conclusions: 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.

Keywords: Essential oils, anticancer volatile molecules, phosphatidylinositol-3-kinase pathway, pharmacophore, docking, inhaling application against lung cancer

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Article Details

Year: 2017
(E-pub Abstract Ahead of Print)
DOI: 10.2174/1871520617666170327105706
Price: $95